Gastro Health Magazine - 2012 Issue

Cancer Prevention

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Gastro Health & FIU

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Pathology Explained

Pediatric News you need to know

JAMIE LEE CURTIS

“Almost half of Americans have some day-to-day problems with digestion — some minor and some profound.”-JLC

5 Lifestyle

Healthy

Changes

IMPROVING your DIGESTIVE HEALTH

2012 Edition

C onvenient &C ompassionate Galloway Endoscopy Center is an accredited surgical facility offering diagnostic and therapeutic gastrointestinal procedures in a comfortable and convenient outpatient setting.

Our compassionate, bilingual staff provides top-quality care while assisting our experienced and highly skilled doctors.

Best of all, because of advances in medical technology, endoscopic procedures can be safely performed outside the hospital, so you can return to the comfort of your home the same day as your procedure.

You have a choice in healthcare. Isn’t it time you got treated better?

A division of Baptist Surgery and Endoscopy Centers

7500 SW 87 Avenue, Suite 101 • Miami, FL 33173 • GallowayEndoscopy.com • 305-595-9511 Committed to our faith-based charitable mission of medical excellence

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1 Up to 100 times more potent than the average probiotic Up to 100 times more potent than the average probiotic • VSL#3 is a medical food & must only be used under • VSL#3 is a medical food & must only be used under medical supervision medical supervision • Clinically proven in double-blind, placebo-controlled trials to • Clinically proven in double-blind, placebo-controlled trials to provide significant benefit in the dietary management of provide significant benefit in the dietary management of irritable bowel syndrome, ulcerative colitis and an ileal pouch irritable bowel syndrome, ulcerative colitis and an ileal pouch • Refrigerated VSL#3 contains 8 proprietary strains of live bacteria • Refrigerated VSL#3 contains 8 proprietary strains of live bacteria providing 112.5 billion to 900 billion CFU per serving making it providing 112.5 billion to 900 billion CFU per serving making it 1 1 one of the most potent probiotics available one of the most potent probiotics available

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1. Source: AC Nielsen 12.2009 Average CFU claimed by product manufacturer was approx. 4 billion CFU per capsule or tablet 1. Source: AC Nielsen 12.2009 Average CFU claimed by product manufacturer was approx. 4 billion CFU per capsule or tablet

For further information, please speak with your healthcare professional For further information, please speak with your healthcare professional

www.vsl3.com www.vsl3.com

Gastro Health

Gastro Health Welcomes you

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The physicians and staff of Gastro Health are pleased to present the 2012 issue of Gastro Health Magazine. Inside you will find informative and educational articles on various digestive health topics such as inflammatory bowel disease, diverticulitis and gastroesophageal reflux, among others. We are also delighted to feature Jamie Lee Curtis, who shares her experiences with everyday health.

This magazine represents our group’s vision: to deliver quality medical care and preventative medicine to all patients; align ourselves with the finest physicians practicing medicine in South Florida; and developing ancillary services that improve our patients’ quality of care and customer experience.

The physicians, nurses, nutritionists and office staff of Gastro Health seek to exceed the expectations of the patient experience by treating everyone as an immediate part of our family. Thanks to patients’ feedback, we have received a 98% satisfaction with our services – confirming the dedication to excellence within our care centers. We are proud to have several of our physicians make the 2011 US News & World Report’s prestigious Top Doctor’s List.

Our physicians, allied professionals and staff will continue to achieve excellence in medical care, heal and prevent illness through integrated efforts in the field of digestive care, while always caring for you and the ones you love.

Alejandro Fernandez, MBA, CMPE Chief Executive Officer

9500 South Dadeland Boulevard, Suite 802 Miami, FL 33156 T. 305.468.4180 www.gastrohealth.com

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Inside this issue

Preventing Colon Cancer Can't Stomach Cancer

Inside the Bacteria: Helicobacter Pylori My Life: Jaime Lee Curtis Evaluation of Swallowing The Word is GERD Physician Directory Pediatric News: Spit Happens Surgical Treatments for Colon Cancer Inflammatory Bowel Disease FIU and Gastro Health Working Hand in Hand Imaging Insights What You Might Not Know About Antibiotics Word of the Day: Pathology A New Era for the Treatment of Hepatitis C Feeling the Burn?

Dealing with Diverticulitis Designed and Published by:

11900 Biscayne Boulevard, Suite 100 Miami, FL 33181 T. 305.820.0690

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GASTRO HEALTH MAGAZINE • 2012

Cover Photo: © Kurt Krieger/Corbis

info@creativemindworks.com All rights reserved.

Preventing Colon Cancer What is Colorectal Cancer?

We all know it as “Colon Cancer” – the malignant growth that develops in the colon or rectum. The most common type of colon cancer starts out as a simple polyp, an abnormal growth of tissue that protrudes from a mucous membrane. According to multiple sources, it takes a minimum of 5-10 years for that polyp to become malignant. If it is discovered and removed prior to that transformation, chances of dying from colon cancer drop dramatically. Unfortunately, polyps have very few symptoms. This year, approximately 50,000 Americans will die from colon cancer.

What is a Colonoscopy?

The ultimate goal is the prevention of cancer by detecting and removing any precancerous growths at an early stage. A colonoscopy is considered the “gold standard” of screening and diagnostic tests for colorectal cancer. This procedure allows for direct visual examination of the colon and rectum, which helps to locate even the smallest polyps before they have a chance to become malignant. If a polyp is found, it may be removed by passing a wire loop through the colonoscope and cut from the colon wall with an electric current.

HIGH RISK

LOW RISK

How often should you undergo a Colonoscopy?

PATIENT DESCRIPTION

EVALUATION INDICATED

AGE 50 No Risk Factors

Colonoscopy beginning at age 50 (For African Americans beginning at the age of 45)

Family history of colon cancer or polyps

Colonoscopy beginning 10 years younger than the age the relative was diagnosed

Blood in stool or iron deficiency anemia, rectal bleeding, or a change in bowel habit

Colonoscopy now

Ulcerative Colitis or Crohn’s Disease

Yearly colonoscopy, after 10 years of disease

Personal history of colon cancer or polyps

Regular screening colonoscopy as determined by your physician*

OTHER

INDIVIDUALIZED APPROACH

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Other gastrointestinal symptoms which may include; abdominal pain, narrow stools, constipation, diarrhea, "gas" or bloating, Family history of breast, gynecological, abdominal, colon or other gastrointestinal cancers.

GASTRO HEALTH MAGAZINE • 2012

Preparing for a Colonoscopy The colon should be thoroughly emptied of all fecal matter to facilitate visualization. In order to limit or eliminate the discomfort during the procedure, sedation is usually provided.

Sedation allows the best possible visualization and smoothest possible maneuvering of the scope during the procedure.

Thorough preparation is essential, so all physicians provide the best guidance for their patients.

The advantages of a Colonoscopy New studies suggest that colorectal cancer screening by colonoscopy leads to higher polyp detection rates. It has numerous advantages, including screening, diagnosis, and removal of polyps in one single visit. Colonoscopy also has the longest rescreening interval of all forms of testing; if normal, the exam does not need to be repeated for 10 years.

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Lifestyle changes to reduce your risk of Colorectal Cancer

1. Eat a variety of fruits, vegetables and whole grains 2. Limit the amount of alcohol you drink 3. Do not smoke 4. Exercise and be physically active 5. Maintain a healthy weight

© 2009 Debbie’s Dream Foundation, Inc. doing business as Can’t Stomach Cancer: The Foundation of Debbie’s Dream (CSC). All CSC logos and taglines are trademarks and the exclusive property of CSC and may be registered in the United States or elsewhere.

Gastro Health

For the person diagnosed with stomach cancer, there is an urgency to get the best treatment immediately. However, there are few sources of dependable information about this disease.

Can’t Stomach Cancer: the Foundation of Debbie’s Dream (CSC) is a 501(c)(3) organization dedicated to funding stomach cancer research, raising awareness about the disease, facilitating enrollment in clinical trials, and providing education and support internationally for patients, families, and caregivers. The ultimate goal of Can’t Stomach Cancer is to make the cure for stomach cancer a reality.

STOMACH CANCER: THE FACTS • Stomach cancer, also known as gastric cancer, is one of the leading causes of cancer death worldwide - second in men and fourth in women.

• Each year nearly 930,000 people worldwide are diagnosed with stomach cancer, and approximately 700,000 die.

• According to the American Cancer Society, approximately 22,000 Americans are diagnosed with stomach cancer each year, and more than 10,000 will die within the first year.

• Currently, more than 64,000 Americans are living with stomach cancer, and studies have shown that the incidence of stomach cancer is rising.

• Per cancer death, gastric cancer receives the least amount of federal funding.

• There is little research being conducted on stomach cancer for a variety of reasons, including lack of funding and few physicians specializing in this disease.

CSC STRATEGIC INITIATIVES • Raise awareness through educational programs and events about the reality of stomach cancer and the toll it takes on patients and their families • Inform stomach cancer patients, their families, caregivers, and healthcare professionals through educational materials and symposia • Provide no-cost support and objective, reliable information about treatment options, ongoing research, and clinical trials • Serve as the primary resource for health care professionals to refer their patients • Fund research directly and through focused public policy efforts to increase federal funding • Encourage collaboration and information sharing among medical professionals, researchers, scientists, pharmaceutical companies, public agencies, and patients

CSC MILESTONES Can’t Stomach Cancer held the first ever Stomach Cancer Education Symposium which featured lectures by renowned doctors from leading cancer centers and was viewed internationally via webcast. CSC launched its Patient Resource Education Program (PREP) to provide education, resources, and support internationally for stomach cancer patients, families, caregivers, and health care providers on its toll-free hotline at (855) 475-1200. Patients can speak to each other to share knowledge and learn from each other’s experiences. The foundation has events across the country and helps patients all over the world.

ABOUT THE FOUNDER Debbie Zelman is a rare individual who turned personal misfortune into an opportunity to make a difference in the world. In April 2008 she was diagnosed with advanced, incurable stomach cancer. In the course of searching for treatment options, she quickly learned how difficult this disease is to detect and treat. Working closely with her doctors in academic and community settings, Debbie began responding to treatment. She then decided to use her experience, skills, tenacity, and broad network of friends and supporters to start a movement to raise awareness about the disease, fund research, and help other patients.

In April 2009 Debbie’s Dream Foundation was started as a non-profit organization that became a strong voice for stomach cancer advocacy in South Florida. However, Debbie realized that the fight against stomach cancer was bigger than her and her community and therefore needed a broader stage. To fulfill her dream of a world free of stomach cancer, she initiated a call to action, a rallying cry, a declaration once and for all that as a nation and a world we will stand up to this disease. CSC has emerged as the leader for this under-recognized and under-funded disease.

CSC IS HUNGRY FOR A CURE! JOIN US AND TOGETHER WE CAN MAKE DEBBIE’S DREAM A REALITY! For more information, lectures, numerous resources and related links visit: www.CantStomachCancer.org Office: (954) 475-1200 | Toll-Free Hotline: (855) 475-1200 | Info@CantStomachCancer.org | 6919 West Broward Boulevard, #309, Plantation, FL 33317

Gastro Health

Investigative Overview Inside the Bacteria: Helicobacter Pylori

Andrew Sable, MD Board Certified Gastroenterologist

Helicobacter Pylori (or H. Pylori) is likely one of the most common bacterial infections worldwide. In fact, it has been estimated that close to 50% of the world’s population may be infected.

H. Pylori is a bacteria found in the stomach. It was initially identified in 1982 when scientists discovered that this particular bacteria was present in patients suffering from chronic gastritis and gastric ulcers. Infection with H. Pylori can contribute to the development of gastritis (inflammation of the stomach), gastric or duodenal ulcers, and dyspepsia (upset stomach and or indigestion). Prior to the discovery of H. Pylori, it was presumed that these conditions were more likely due to medications such as anti-inflammatories and steroids, alcohol and even stress. Since then, H. Pylori has also been identified as a risk factor for the development of gastric cancer.

Individuals who have H. Pylori likely acquire the infection when the bacteria is swallowed. It may be present in food, fluids or even utensils and is usually passed on from one person to another. And while often acquired as a youth, H. Pylori infection rates do increase with aging.

Infection with H. Pylori is more frequently found in people from developing countries and those living in large cities with diverse populations.

Additionally, infection rates tend to be higher in areas of poor sanitation and crowded living

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GASTRO HEALTH MAGAZINE • 2012

spaces. It is important to keep in mind that while H. Pylori can cause several conditions, many if not most (approximately 80%) of those infected will remain asymptomatic.

It may be present in food, fluids or even utensils and is usually passed on from one person to another.

How is H. Pylori infection diagnosed?

Presently, there are several ways to detect the presence of H. Pylori in an individual.

There are specific stool tests, serology (blood tests) and a breathing test, all of which can be done in a doctor’s office. Perhaps the most accurate and definitive way to diagnose this bacteria is during endoscopy. This is a procedure performed by a gastroenterologist during which a flexible camera is introduced into the stomach through the mouth and tissue samples of the stomach are removed for analysis. This painless procedure can be done as an outpatient very safely and rapidly.

This bacteria has been implicated in chronic gastritis and dyspepsia. Patients suffering from these conditions may have nausea, bloating and abdominal discomfort characterized by burning

and upper abdominal pain. H. Pylori is also often the cause of both gastric and duodenal ulcers.

When H. Pylori is found in the setting of ulcers, it should be treated. This will help both heal the ulcers and prevent their recurrence. Stomach cancer and certain types of gastric lymphomas may also be related to infection with H. Pylori.

It is important to understand that while H. Pylori infection is very common, very few of those who have it will ever develop these types of cancers.

Since infection with H. Pylori is so common, and so few people are affected or have symptoms, it is not recommended to test for this bacteria unless your doctor determines that it may be necessary. There are several treatment regimens that exist, but all require multiple medications. Often, two antibiotics are used along with antacid medications. The specific medications and duration of treatment should be determined on an individual basis by your physician. Testing to ensure eradication of H. Pylori is not always necessary but may be important and should be discussed with your doctor.

While the incidence of H. Pylori in Western countries is on decline, detecting and treating H. Pylori may be an important part of your well-being and overall health. Your physician can help assist you in determining if testing for H. Pylori is important to your healthcare.

For adult patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response to conventional therapy

INFUSE CHANGE Only REMICADE® maintains mucosal healing and delivers sustained remission

• Mucosal healing in patients receiving REMICADE® 5 mg/kg—Week 8: 62% (75/121) vs 34% (41/121) placebo (P<0.001); Week 54: 45% (55/121) vs 18% (22/121) placebo (P<0.001)1,2*†‡ • Clinical remission in patients receiving REMICADE® 5 mg/kg—Week 8: 39% (47/121) vs 15% (18/121) placebo (P<0.001); Week 54: 35% (42/121) vs 17% (20/121) placebo (P<0.01)1,2*†§ • Clinical response in patients receiving REMICADE® 5 mg/kg—Week 8: 69% (84/121) vs 37% (45/121) placebo (P<0.001)1,2*†|| * The safety and efficacy of REMICADE® was evaluated in ACT 1 (N=364) (ACT=Active Ulcerative Colitis Trial), a randomized, double-blind, placebo-controlled, multicenter trial conducted in patients with moderately to severely active ulcerative colitis who had an inadequate response or were intolerant to conventional therapy. Patients presented with a Mayo score between 6 and 12, and an endoscopy subscore of ≥2. Prior failed or intolerable therapies in ACT 1 included oral corticosteroids, 6-mercaptopurine (6-MP), or azathioprine (AZA). Patients were randomized to the following treatment groups: REMICADE® 5 mg/kg (n=121), REMICADE® 10 mg/kg (n=122), or placebo (n=121). Infusions were administered at Weeks 0, 2, and 6, and every 8 weeks thereafter through Week 46. Final efficacy evaluations were completed 8 weeks following the last infusion. Concomitant treatment with stable doses of 5-ASA, corticosteroids, and/or immunomodulators was permitted throughout the study. Of patients receiving steroids at baseline, tapering was allowed beginning at Week 8. The primary efficacy endpoint was clinical response at Week 8; secondary endpoints included remission and mucosal healing. † Patients who had a prohibited change in medication, had an ostomy or colectomy, or discontinued study infusions due to lack of efficacy are considered to not be in clinical response, clinical remission, or mucosal healing from the time of the event forward. ‡ Mucosal healing was defined as an endoscopy subscore of 0 or 1. Moderate to severe disease: marked erythema, absent vascular pattern, friability, erosions, spontaneous bleeding, ulceration. § Clinical remission was defined as a Mayo score of ≤2 points with no individual subscore >1 point. || Clinical response was defined as a decrease in Mayo score of ≥30% and ≥3 points, accompanied by a decrease in rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1.

REMICADE® is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

IMPORTANT SAFETY INFORMATION FOR REMICADE® SERIOUS INFECTIONS Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.

Reported infections include: - Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®.3, 4 Treatment for latent infection should be initiated prior to treatment with REMICADE®.

- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

- Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Continued on next page

IMPORTANT SAFETY INFORMATION FOR REMICADE® (CONTINUED)

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The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE®. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

CONTRAINDICATIONS REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal.

Patients should be tested for HBV infection before initiating REMICADE®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment.

Exercise caution when considering resumption of REMICADE® and monitor patients closely.

HEPATOTOXICITY Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear.

Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.

NEUROLOGIC EVENTS TNF inhibitors, including REMICADE®, have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY Treatment with REMICADE® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

ADVERSE REACTIONS In clinical trials, the most common REMICADE® adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

USE WITH OTHER DRUGS The use of REMICADE® in combination with anakinra, abatacept or tocilizumab is not recommended. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

VACCINATIONS Live vaccines should not be given with REMICADE®. Bring pediatric patients up to date with all vaccinations prior to initiating REMICADE®. Exercise caution in the administration of live vaccines to infants born to female patients treated with REMICADE® during pregnancy.

Please see Brief Summary of full Prescribing Information accompanying this advertisement.

References: 1. REMICADE® Prescribing information. Janssen Biotech, Inc. 2. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462-2476. 3. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.

4. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

© Janssen Biotech, Inc. 2012

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REMICADE (infliximab) Lyophilized Concentrate for Injection, for Intravenous Use Brief Summary of Full Prescribing Information WARNING: SERIOUS INFECTIONS and MALIGNANCY SERIOUS INFECTIONS Patients treated with REMICADE® are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions and Adverse Reactions] Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

REMICADE should be discontinued if a patient develops a serious infection or sepsis.

Reported infections include: • Active tuberculosis, including reactivation of latent tuberculosis.

Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before REMICADE use and during therapy.1,2 Treatment for latent infection should be initiated prior to REMICADE use.

• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis.

Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

• Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with REMICADE should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with REMICADE, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE [see Warnings and Precautions].

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE at or prior to diagnosis.

CONTRAINDICATIONS: REMICADE at doses >5 mg/kg should not be administered to patients with moderate to severe heart failure. In a randomized study evaluating REMICADE in patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), REMICADE treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure [see Warnings and Precautions and Adverse Reactions]. REMICADE should not be re-administered to patients who have experienced a severe hypersensitivity reaction to REMICADE. Additionally, REMICADE should not be administered to patients with known hypersensitivity to inactive components of the product or to any murine proteins. WARNINGS AND PRECAUTIONS: Serious Infections: Patients treated with REMICADE are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease. Treatment with REMICADE should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients: • with chronic or recurrent infection; • who have been exposed to tuberculosis; • with a history of an opportunistic infection • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or • with underlying conditions that may predispose them to infection. Tuberculosis: Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving REMICADE, including patients who have previously received treatment for latent or active tuberculosis. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating REMICADE and periodically during therapy. Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been

REMICADE® (infliximab) shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating REMICADE, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Anti-tuberculosis therapy should also be considered prior to initiation of REMICADE in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.

Tuberculosis should be strongly considered in patients who develop a new infection during REMICADE treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis. Monitoring: Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with REMICADE, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with REMICADE. REMICADE should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with REMICADE should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated. Invasive Fungal Infections: For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy. Malignancies: Malignancies, some fatal, have been reported among children, adolescents and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), including REMICADE. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports. Lymphomas: In the controlled portions of clinical trials of all the TNF-blocking agents, more cases of lymphoma have been observed among patients receiving a TNF blocker compared with control patients. In the controlled and open-label portions of REMICADE clinical trials, 5 patients developed lymphomas among 5707 patients treated with REMICADE (median duration of follow-up 1.0 years) vs. 0 lymphomas in 1600 control patients (median duration of follow-up 0.4 years). In rheumatoid arthritis patients, 2 lymphomas were observed for a rate of 0.08 cases per 100 patient-years of follow-up, which is approximately three-fold higher than expected in the general population. In the combined clinical trial population for rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and plaque psoriasis, 5 lymphomas were observed for a rate of 0.10 cases per 100 patient-years of follow-up, which is approximately four-fold higher than expected in the general population. Patients with Crohn’s disease, rheumatoid arthritis or plaque psoriasis, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy.

Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia. Hepatosplenic T-cell lymphoma (HSTCL): Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with REMICADE at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to REMICADE or REMICADE in combination with these other immunosuppressants.When treating patients with inflammatory bowel disease, particularly in adolescents and young adults, consideration of whether to use REMICADE alone or in combination with other immunosuppressants should take into account a possibility that there is a higher risk of HSTCL with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with REMICADE monotherapy from the clinical trial data [see Warnings and Precautions and Adverse Reactions]. Other Malignancies: In the controlled portions of clinical trials of some TNF-blocking agents including REMICADE, more malignancies (excluding lymphoma and nonmelanoma skin cancer [NMSC]) have been observed in patients receiving

REMICADE® (infliximab)

REMICADE® (infliximab)

those TNF-blockers compared with control patients. During the controlled portions of REMICADE trials in patients with moderately to severely active rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and plaque psoriasis, 14 patients were diagnosed with malignancies (excluding lymphoma and NMSC) among 4019 REMICADEtreated patients vs. 1 among 1597 control patients (at a rate of 0.52/100 patient-years among REMICADE-treated patients vs. a rate of 0.11/100 patient-years among control patients), with median duration of follow-up 0.5 years for REMICADE-treated patients and 0.4 years for control patients. Of these, the most common malignancies were breast, colorectal, and melanoma.

The rate of malignancies among REMICADE-treated patients was similar to that expected in the general population whereas the rate in control patients was lower than expected. In a clinical trial exploring the use of REMICADE in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, the majority of lung or head and neck origin, were reported in REMICADE-treated patients compared with control patients. All patients had a history of heavy smoking [see Adverse Reactions]. Prescribers should exercise caution when considering the use of REMICADE in patients with moderate to severe COPD. Psoriasis patients should be monitored for nonmelanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. In the maintenance portion of clinical trials for REMICADE, NMSCs were more common in patients with previous phototherapy [see Adverse Reactions]. The potential role of TNF-blocking therapy in the development of malignancies is not known [see Adverse Reactions]. Rates in clinical trials for REMICADE cannot be compared to rates in clinical trials of other TNF-blockers and may not predict rates observed in a broader patient population. Caution should be exercised in considering REMICADE treatment in patients with a history of malignancy or in continuing treatment in patients who develop malignancy while receiving REMICADE. Hepatitis B Virus Reactivation: Use of TNF blockers, including REMICADE, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal.

The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Patients should be tested for HBV infection before initiating TNF blocker therapy, including REMICADE. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with TNF blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, TNF blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF blocker therapy in this situation and monitor patients closely. Hepatotoxicity: Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported rarely in postmarketing data in patients receiving REMICADE. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between 2 weeks to more than 1 year after initiation of REMICADE; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥ 5 times the upper limit of normal) develop, REMICADE should be discontinued, and a thorough investigation of the abnormality should be undertaken. In clinical trials, mild or moderate elevations of ALT and AST have been observed in patients receiving REMICADE without progression to severe hepatic injury [see Adverse Reactions]. Patients with Heart Failure: REMICADE has been associated with adverse outcomes in patients with heart failure, and should be used in patients with heart failure only after consideration of other treatment options. The results of a randomized study evaluating the use of REMICADE in patients with heart failure (NYHA Functional Class III/IV) suggested higher mortality in patients who received 10 mg/kg REMICADE, and higher rates of cardiovascular adverse events at doses of 5 mg/kg and 10 mg/kg. There have been post-marketing reports of worsening heart failure, with and without identifiable precipitating factors, in patients taking REMICADE. There have also been rare post-marketing reports of new onset heart failure, including heart failure in patients without known pre-existing cardiovascular disease. Some of these patients have been under 50 years of age. If a decision is made to administer REMICADE to patients with heart failure, they should be closely monitored during therapy, and REMICADE should be discontinued if new or worsening symptoms of heart failure appear [see Contraindications and Adverse Reactions]. Hematologic Reactions: Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients receiving REMICADE. The causal relationship to REMICADE therapy remains unclear. Although no high-risk group(s) has been identified, caution should be exercised in patients being treated with REMICADE who have ongoing or a history of significant hematologic abnormalities. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on REMICADE. Discontinuation of REMICADE therapy should be considered in patients who develop significant

hematologic abnormalities. Hypersensitivity: REMICADE has been associated with hypersensitivity reactions that vary in their time of onset and required hospitalization in some cases. Most hypersensitivity reactions, which include urticaria, dyspnea, and/or hypotension, have occurred during or within 2 hours of REMICADE infusion. However, in some cases, serum sickness-like reactions have been observed in patients after initial REMICADE therapy (i.e., as early as after the second dose), and when REMICADE therapy was reinstituted following an extended period without REMICADE treatment. Symptoms associated with these reactions include fever, rash, headache, sore throat, myalgias, polyarthralgias, hand and facial edema and/or dysphagia. These reactions were associated with a marked increase in antibodies to infliximab, loss of detectable serum concentrations of infliximab, and possible loss of drug efficacy. REMICADE should be discontinued for severe hypersensitivity reactions. Medications for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids and/or epinephrine) should be available for immediate use in the event of a reaction [see Adverse Reactions].

In rheumatoid arthritis, Crohn’s disease and psoriasis clinical trials, re-administration of REMICADE after a period of no treatment resulted in a higher incidence of infusion reactions relative to regular maintenance treatment [see Adverse Reactions]. In general, the benefit-risk of re-administration of REMICADE after a period of no-treatment, especially as a re-induction regimen given at weeks 0, 2 and 6, should be carefully considered.

In the case where REMICADE maintenance therapy for psoriasis is interrupted, REMICADE should be reinitiated as a single dose followed by maintenance therapy. Neurologic Reactions: REMICADE and other agents that inhibit TNF have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Prescribers should exercise caution in considering the use of REMICADE in patients with these neurologic disorders and should consider discontinuation of REMICADE if these disorders develop. Use with Anakinra: Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents.

Therefore, the combination of REMICADE and anakinra is not recommended.

Use with Abatacept: In clinical studies, concurrent administration of TNF-blocking agents and abatacept have been associated with an increased risk of infections including serious infections compared with TNF-blocking agents alone, without increased clinical benefit. Therefore, the combination of REMICADE and abatacept is not recommended [see Drug Interactions].

Switching between Biological Disease-Modifying Antirheumatic Drugs (DMARDs): Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

Autoimmunity: Treatment with REMICADE may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with REMICADE, treatment should be discontinued [see Adverse Reactions]. Vaccinations: No data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines in patients receiving anti-TNF therapy. It is recommended that live vaccines not be given concurrently. Caution is advised in the administration of live vaccines to infants born to female patients treated with REMICADE during pregnancy since REMICADE is known to cross the placenta and has been detected up to 6 months in the serum of infants born to female patients treated with REMICADE during pregnancy. It is recommended that all pediatric patients be brought up to date with all vaccinations prior to initiating REMICADE therapy. The interval between vaccination and initiation of REMICADE therapy should be in accordance with current vaccination guidelines. ADVERSE REACTIONS: Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not predict the rates observed in broader patient populations in clinical practice. Adverse Reactions in Adults: The data described herein reflect exposure to REMICADE in 4779 adult patients (1304 patients with rheumatoid arthritis, 1106 patients with Crohn’s disease, 202 with ankylosing spondylitis, 293 with psoriatic arthritis, 484 with ulcerative colitis, 1373 with plaque psoriasis, and 17 patients with other conditions), including 2625 patients exposed beyond 30 weeks and 374 exposed beyond 1 year. [For information on adverse reactions in pediatric patients see Adverse Reactions.]

One of the most-common reasons for discontinuation of treatment was infusion-related reactions (e.g., dyspnea, flushing, headache and rash).

Infusion-related Reactions: An infusion reaction was defined in clinical trials as any adverse event occurring during an infusion or within 1 hour after an infusion. In phase 3 clinical studies, 18% of REMICADE-treated patients experienced an infusion reaction compared to 5% of placebo-treated patients.

Of infliximab-treated patients who had an infusion reaction during the induction period, 27% experienced an infusion reaction during the maintenance period.

Of patients who did not have an infusion reaction during the induction period, 9% experienced an infusion reaction during the maintenance period. Among all REMICADE infusions, 3% were accompanied by nonspecific symptoms such as fever or chills, 1% were accompanied by cardiopulmonary reactions (primarily chest pain, hypotension, hypertension or dyspnea), and <1% were accompanied by pruritus, urticaria, or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions. Serious infusion reactions

REMICADE® (infliximab)

REMICADE® (infliximab)

occurred in <1% of patients and included anaphylaxis, convulsions, erythematous rash and hypotension. Approximately 3% of patients discontinued REMICADE because of infusion reactions, and all patients recovered with treatment and/or discontinuation of the infusion. REMICADE infusions beyond the initial infusion were not associated with a higher incidence of reactions. The infusion reaction rates remained stable in psoriasis through 1 year in psoriasis Study I. In psoriasis Study II, the rates were variable over time and somewhat higher following the final infusion than after the initial infusion. Across the 3 psoriasis studies, the percent of total infusions resulting in infusion reactions (i.e., an adverse event occurring within 1 hour) was 7% in the 3 mg/kg group, 4% in the 5 mg/kg group, and 1% in the placebo group.

Patients who became positive for antibodies to infliximab were more likely (approximately two- to three-fold) to have an infusion reaction than were those who were negative. Use of concomitant immunosuppressant agents appeared to reduce the frequency of both antibodies to infliximab and infusion reactions [see Adverse Reactions and Drug Interactions]. Infusion reactions following re-administration: In a clinical trial of patients with moderate to severe psoriasis designed to assess the efficacy of long-term maintenance therapy versus re-treatment with an induction regimen of REMICADE following disease flare, 4% (8/219) of patients in the re-treatment therapy arm experienced serious infusion reactions versus < 1% (1/222) in the maintenance therapy arm. Patients enrolled in this trial did not receive any concomitant immunosuppressant therapy. In this study, the majority of serious infusion reactions occurred during the second infusion at Week 2. Symptoms included, but were not limited to, dyspnea, urticaria, facial edema, and hypotension. In all cases, REMICADE treatment was discontinued and/or other treatment instituted with complete resolution of signs and symptoms. Delayed Reactions/Reactions Following Re-administration: In psoriasis studies, approximately 1% of REMICADE-treated patients experienced a possible delayed hypersensitivity reaction, generally reported as serum sickness or a combination of arthralgia and/or myalgia with fever and/or rash. These reactions generally occurred within 2 weeks after repeat infusion. Infections: In REMICADE clinical studies, treated infections were reported in 36% of REMICADE-treated patients (average of 51 weeks of follow-up) and in 25% of placebo-treated patients (average of 37 weeks of follow-up). The infections most frequently reported were respiratory tract infections (including sinusitis, pharyngitis, and bronchitis) and urinary tract infections. Among REMICADEtreated patients, serious infections included pneumonia, cellulitis, abscess, skin ulceration, sepsis, and bacterial infection. In clinical trials, 7 opportunistic infections were reported; 2 cases each of coccidioidomycosis (1 case was fatal) and histoplasmosis (1 case was fatal), and 1 case each of pneumocystosis, nocardiosis and cytomegalovirus. Tuberculosis was reported in 14 patients, 4 of whom died due to miliary tuberculosis. Other cases of tuberculosis, including disseminated tuberculosis, also have been reported post-marketing. Most of these cases of tuberculosis occurred within the first 2 months after initiation of therapy with REMICADE and may reflect recrudescence of latent disease [see Warnings and Precautions]. In the 1-year placebo-controlled studies RA I and RA II, 5.3% of patients receiving REMICADE every 8 weeks with MTX developed serious infections as compared to 3.4% of placebo patients receiving MTX. Of 924 patients receiving REMICADE, 1.7% developed pneumonia and 0.4% developed TB, when compared to 0.3% and 0.0% in the placebo arm respectively. In a shorter (22-week) placebo-controlled study of 1082 RA patients randomized to receive placebo, 3 mg/kg or 10 mg/kg REMICADE infusions at 0, 2, and 6 weeks, followed by every 8 weeks with MTX, serious infections were more frequent in the 10 mg/kg REMICADE group (5.3%) than the 3 mg/kg or placebo groups (1.7% in both). During the 54-week Crohn’s II Study, 15% of patients with fistulizing Crohn’s disease developed a new fistula-related abscess. In REMICADE clinical studies in patients with ulcerative colitis, infections treated with antimicrobials were reported in 27% of REMICADE-treated patients (average of 41 weeks of follow-up) and in 18% of placebo-treated patients (average 32 weeks of follow-up). The types of infections, including serious infections, reported in patients with ulcerative colitis were similar to those reported in other clinical studies. The onset of serious infections may be preceded by constitutional symptoms such as fever, chills, weight loss, and fatigue. The majority of serious infections, however, may also be preceded by signs or symptoms localized to the site of the infection. Autoantibodies/ Lupus-like Syndrome: Approximately half of REMICADE-treated patients in clinical trials who were antinuclear antibody (ANA) negative at baseline developed a positive ANA during the trial compared with approximately one-fifth of placebo-treated patients. Anti-dsDNA antibodies were newly detected in approximately one-fifth of REMICADE-treated patients compared with 0% of placebo-treated patients. Reports of lupus and lupus-like syndromes, however, remain uncommon. Malignancies: In controlled trials, more REMICADE-treated patients developed malignancies than placebo-treated patients [see Warnings and Precautions]. In a randomized controlled clinical trial exploring the use of REMICADE in patients with moderate to severe COPD who were either current smokers or ex-smokers, 157 patients were treated with REMICADE at doses similar to those used in rheumatoid arthritis and Crohn’s disease. Of these REMICADE-treated patients, 9 developed a malignancy, including 1 lymphoma, for a rate of 7.67 cases per 100 patient-years of follow-up (median duration of follow-up 0.8 years; 95% CI 3.51 - 14.56). There was 1 reported malignancy among 77 control patients for a rate of 1.63 cases per 100 patient-years of follow-up (median duration of follow-up 0.8 years; 95% CI 0.04 - 9.10). The majority of the malignancies developed in the lung or head and neck. Patients with Heart Failure: In a randomized study evaluating REMICADE in moderate to severe heart failure (NYHA Class III/IV; left ventricular ejection fraction ≤ 35%), 150 patients were

randomized to receive treatment with 3 infusions of REMICADE 10 mg/kg, 5 mg/kg, or placebo, at 0, 2, and 6 weeks. Higher incidences of mortality and hospitalization due to worsening heart failure were observed in patients receiving the 10 mg/kg REMICADE dose. At 1 year, 8 patients in the 10 mg/kg REMICADE group had died compared with 4 deaths each in the 5 mg/kg REMICADE and the placebo groups. There were trends toward increased dyspnea, hypotension, angina, and dizziness in both the 10 mg/kg and 5 mg/kg REMICADE treatment groups, versus placebo. REMICADE has not been studied in patients with mild heart failure (NYHA Class I/II) [see Contraindications and Warnings and Precautions]. Immunogenicity: Treatment with REMICADE can be associated with the development of antibodies to infliximab. The assay used to measure anti-infliximab antibodies in patient samples is subject to interference by serum infliximab, possibly resulting in an underestimation of the rate of patient antibody formation. The incidence of antibodies to infliximab in patients given a 3-dose induction regimen followed by maintenance dosing was approximately 10% as assessed through 1 to 2 years of REMICADE treatment. A higher incidence of antibodies to infliximab was observed in Crohn’s disease patients receiving REMICADE after drug-free intervals >16 weeks. In a study of psoriatic arthritis in which 191 patients received 5 mg/kg with or without MTX, antibodies to infliximab occurred in 15% of patients. The majority of antibody-positive patients had low titers. Patients who were antibody-positive were more likely to have higher rates of clearance, reduced efficacy and to experience an infusion reaction [see Adverse Reactions] than were patients who were antibody negative. Antibody development was lower among rheumatoid arthritis and Crohn’s disease patients receiving immunosuppressant therapies such as 6-MP/AZA or MTX. In the psoriasis Study II, which included both the 5 mg/kg and 3 mg/kg doses, antibodies were observed in 36% of patients treated with 5 mg/kg every 8 weeks for 1 year, and in 51% of patients treated with 3 mg/kg every 8 weeks for 1 year. In the psoriasis Study III, which also included both the 5 mg/kg and 3 mg/kg doses, antibodies were observed in 20% of patients treated with 5 mg/kg induction (weeks 0, 2 and 6), and in 27% of patients treated with 3 mg/kg induction. Despite the increase in antibody formation, the infusion reaction rates in Studies I and II in patients treated with 5 mg/kg induction followed by every 8 week maintenance for 1 year and in Study III in patients treated with 5 mg/kg induction (14.1%-23.0%) and serious infusion reaction rates (<1%) were similar to those observed in other study populations. The clinical significance of apparent increased immunogenicity on efficacy and infusion reactions in psoriasis patients as compared to patients with other diseases treated with REMICADE over the long term is not known. The data reflect the percentage of patients whose test results were positive for antibodies to infliximab in an ELISA assay, and they are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to infliximab with the incidence of antibodies to other products may be misleading. Hepatotoxicity: Severe liver injury, including acute liver failure and autoimmune hepatitis, has been reported rarely in patients receiving REMICADE [see Warnings and Precautions]. Reactivation of hepatitis B virus has occurred in patients receiving TNF-blocking agents, including REMICADE, who are chronic carriers of this virus [see Warnings and Precautions]. In clinical trials in rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis, elevations of aminotransferases were observed (ALT more common than AST) in a greater proportion of patients receiving REMICADE than in controls (Table 1), both when REMICADE was given as monotherapy and when it was used in combination with other immunosuppressive agents. In general, patients who developed ALT and AST elevations were asymptomatic, and the abnormalities decreased or resolved with either continuation or discontinuation of REMICADE, or modification of concomitant medications.

Table 1 Proportion of patients with elevated ALT in clinical trials Proportion of patients with elevated ALT >1 to <3 x ULN ≥3 x ULN ≥5 x ULN Placebo REMICADE Placebo REMICADE Placebo REMICADE 34% 3% 4% <1% <1% Rheumatoid arthritisa 24% 34% 39% 4% 5% 0% 2% Crohn’s diseaseb c 12% 17% 1% 2% <1% <1% Ulcerative colitis d 51% 0% 10% 0% 4% Ankylosing spondylitis 15% 16% 50% 0% 7% 0% 2% Psoriatic arthritise f Plaque psoriasis 24% 49% <1% 8% 0% 3% a Placebo patients received methotrexate while REMICADE patients received both REMICADE and methotrexate. Median follow-up was 58 weeks. b Placebo patients in the 2 Phase 3 trials in Crohn’s disease received an initial dose of 5 mg/kg REMICADE at study start and were on placebo in the maintenance phase. Patients who were randomized to the placebo maintenance group and then later crossed over to REMICADE are included in the REMICADE group in ALT analysis. Median follow-up was 54 weeks. c Median follow-up was 30 weeks. Specifically, the median duration of follow-up was 30 weeks for placebo and 31 weeks for REMICADE. d Median follow-up was 24 weeks for the placebo group and 102 weeks for the REMICADE group. e Median follow-up was 39 weeks for the REMICADE group and 18 weeks for the placebo group. f ALT values are obtained in 2 Phase 3 psoriasis studies with median follow-up of 50 weeks for REMICADE and 16 weeks for placebo.

Adverse Reactions in Psoriasis Studies: During the placebo-controlled portion across the 3 clinical trials up to week 16, the proportion of patients who experienced at least 1 serious adverse reaction (SAE; defined as resulting in

REMICADE® (infliximab)

REMICADE® (infliximab)

death, life threatening, requires hospitalization, or persistent or significant disability/incapacity) was 0.5% in the 3 mg/kg REMICADE group, 1.9% in the placebo group, and 1.6% in the 5 mg/kg REMICADE group. Among patients in the 2 Phase 3 studies, 12.4% of patients receiving REMICADE 5 mg/kg every 8 weeks through 1 year of maintenance treatment experienced at least 1 SAE in Study I. In Study II, 4.1% and 4.7% of patients receiving REMICADE 3 mg/kg and 5 mg/kg every 8 weeks, respectively, through 1 year of maintenance treatment experienced at least 1 SAE. One death due to bacterial sepsis occurred 25 days after the second infusion of 5 mg/kg REMICADE. Serious infections included sepsis, and abscesses. In Study I, 2.7% of patients receiving REMICADE 5 mg/kg every 8 weeks through 1 year of maintenance treatment experienced at least 1 serious infection. In Study II, 1.0% and 1.3% of patients receiving REMICADE 3 mg/kg and 5 mg/kg, respectively, through 1 year of treatment experienced at least 1 serious infection. The most common serious infection (requiring hospitalization) was abscess (skin, throat, and peri-rectal) reported by 5 (0.7%) patients in the 5 mg/kg REMICADE group. Two active cases of tuberculosis were reported: 6 weeks and 34 weeks after starting REMICADE. In the placebo-controlled portion of the psoriasis studies, 7 of 1123 patients who received REMICADE at any dose were diagnosed with at least one NMSC compared to 0 of 334 patients who received placebo. In the psoriasis studies, 1% (15/1373) of patients experienced serum sickness or a combination of arthralgia and/or myalgia with fever, and/or rash, usually early in the treatment course. Of these patients, 6 required hospitalization due to fever, severe myalgia, arthralgia, swollen joints, and immobility. Other Adverse Reactions: Safety data are available from 4779 REMICADE-treated adult patients, including 1304 with rheumatoid arthritis, 1106 with Crohn’s disease, 484 with ulcerative colitis, 202 with ankylosing spondylitis, 293 with psoriatic arthritis, 1373 with plaque psoriasis and 17 with other conditions. [For information on other adverse reactions in pediatric patients, see Adverse Reactions]. Adverse reactions reported in ≥ 5% of all patients with rheumatoid arthritis receiving 4 or more infusions are in Table 2. The types and frequencies of adverse reactions observed were similar in REMICADE-treated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis and Crohn’s disease patients except for abdominal pain, which occurred in 26% of REMICADE-treated patients with Crohn’s disease. In the Crohn’s disease studies, there were insufficient numbers and duration of follow-up for patients who never received REMICADE to provide meaningful comparisons.

Table 2 Adverse reactions occurring in 5% or more of patients receiving 4 or more infusions for rheumatoid arthritis Placebo REMICADE (n=350) (n=1129) Average weeks of follow-up 59 66 Gastrointestinal Nausea 20% 21% Abdominal pain 8% 12% Diarrhea 12% 12% Dyspepsia 7% 10% Respiratory Upper respiratory tract infection 25% 32% Sinusitis 8% 14% Pharyngitis 8% 12% Coughing 8% 12% Bronchitis 9% 10% Skin and appendages disorders Rash 5% 10% Pruritus 2% 7% Body as a whole-general disorders Fatigue 7% 9% Pain 7% 8% Resistance mechanism disorders Fever 4% 7% Moniliasis 3% 5% Central and peripheral nervous system disorders Headache 14% 18% Musculoskeletal system disorders Arthralgia 7% 8% Urinary system disorders Urinary tract infection 6% 8% Cardiovascular disorders, general Hypertension 5% 7%

adults with Crohn’s disease. These differences are discussed in the following paragraphs. The following adverse reactions were reported more commonly in 103 randomized pediatric Crohn’s disease patients administered 5 mg/kg REMICADE through 54 weeks than in 385 adult Crohn’s disease patients receiving a similar treatment regimen: anemia (11%), leukopenia (9%), flushing (9%), viral infection (8%), neutropenia (7%), bone fracture (7%), bacterial infection (6%), and respiratory tract allergic reaction (6%). Infections were reported in 56% of randomized pediatric patients in Study Peds Crohn’s and in 50% of adult patients in Study Crohn’s I. In Study Peds Crohn’s, infections were reported more frequently for patients who received every 8-week as opposed to every 12-week infusions (74% and 38%, respectively), while serious infections were reported for 3 patients in the every 8-week and 4 patients in the every 12-week maintenance treatment group. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was abscess. Pneumonia was reported for 3 patients, (2 in the every 8-week and 1 in the every 12-week maintenance treatment groups). Herpes zoster was reported for 2 patients in the every 8-week maintenance treatment group. In Study Peds Crohn’s, 18% of randomized patients experienced 1 or more infusion reactions, with no notable difference between treatment groups. Of the 112 patients in Study Peds Crohn’s, there were no serious infusion reactions, and 2 patients had non-serious anaphylactoid reactions. In Study Peds Crohn’s, in which all patients received stable doses of 6-MP, AZA, or MTX, excluding inconclusive samples, 3 of 24 patients had antibodies to infliximab. Although 105 patients were tested for antibodies to infliximab, 81 patients were classified as inconclusive because they could not be ruled as negative due to assay interference by the presence of infliximab in the sample. Elevations of ALT up to 3 times the upper limit of normal (ULN) were seen in 18% of pediatric patients in Crohn’s disease clinical trials; 4% had ALT elevations ≥3 x ULN, and 1% had elevations ≥ 5 x ULN. (Median follow-up was 53 weeks.) Pediatric Ulcerative Colitis: Overall, the adverse reactions reported in the pediatric ulcerative colitis trial and adult ulcerative colitis (Study UC I and Study UC II) studies were generally consistent. In a pediatric UC trial, the most common adverse reactions were upper respiratory tract infection, pharyngitis, abdominal pain, fever, and headache. Infections were reported in 31 (52%) of 60 treated patients in the pediatric UC trial and 22 (37%) required oral or parenteral antimicrobial treatment. The proportion of patients with infections in the pediatric UC trial was similar to that in the pediatric Crohn’s disease study (Study Peds Crohn’s) but higher than the proportion in the adults’ ulcerative colitis studies (Study UC I and Study UC II). The overall incidence of infections in the pediatric UC trial was 13/22 (59%) in the every 8 week maintenance treatment group. Upper respiratory tract infection (7/60 [12%]) and pharyngitis (5/60 [8%]) were the most frequently reported respiratory system infections. Serious infections were reported in 12% (7/60) of all treated patients. In the pediatric UC trial, excluding inconclusive samples, 4 of 19 patients had antibodies to infliximab. Although 52 patients were tested, 33 patients were classified as inconclusive because they could not be ruled as negative due to assay interference by the presence of infliximab in the sample. Elevations of ALT up to 3 times the upper limit of normal (ULN) were seen in 17% (10/60) of pediatric patients in the pediatric UC trial; 7% (4/60) had ALT elevations ≥ 3 x ULN, and 2% (1/60) had elevations ≥ 5 x ULN (median follow-up was 49 weeks). Overall, 8 of 60 (13%) treated patients experienced one or more infusion reactions, including 4 of 22 (18%) patients in the every 8-week treatment maintenance group. No serious infusion reactions were reported. In the pediatric UC trial, 45 patients were in the 12 to 17 year age group and 15 in the 6 to 11 year age group. The numbers of patients in each subgroup are too small to make any definitive conclusions about the effect of age on safety events. There were higher proportions of patients with serious adverse events (40% vs. 18%) and discontinuation due to adverse events (40% vs. 16%) in the younger age group than in the older age group.

While the proportion of patients with infections was also higher in the younger age group (60% vs. 49%), for serious infections, the proportions were similar in the two age groups (13% in the 6 to 11 year age group vs. 11% in the 12 to 17 year age group). Overall proportions of adverse reactions, including infusion reactions, were similar between the 6 to 11 and 12 to 17 year age groups (13%).

Post-marketing Experience: Adverse reactions have been reported during post approval use of REMICADE in adult and pediatric patients. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to REMICADE exposure. The following adverse reactions, some with fatal outcome, have been reported during post-approval use of REMICADE: neutropenia [see Warnings and Precautions], interstitial lung disease (including pulmonary fibrosis/interstitial pneumonitis and very rare rapidly progressive disease), idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, pericardial effusion, systemic and cutaneous vasculitis, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, peripheral demyelinating disorders (such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy), new onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar), transverse myelitis, and neuropathies (additional neurologic reactions have also been observed) [see Warnings and Precautions], acute liver failure, jaundice, hepatitis, and cholestasis [see Warnings and Precautions], serious infections [see Warnings and Precautions] and malignancies [see Warnings and Precautions].

Infusion-related Reactions: In post-marketing experience, cases of anaphylactic reactions, including laryngeal/pharyngeal edema and severe bronchospasm, and seizure have been associated with REMICADE

The most common serious adverse reactions observed in clinical trials were infections [see Adverse Reactions]. Other serious, medically relevant adverse reactions ≥ 0.2% or clinically significant adverse reactions by body system were as follows: Body as a whole: allergic reaction, edema; Blood: pancytopenia; Cardiovascular: hypotension; Gastrointestinal: constipation, intestinal obstruction; Central and Peripheral Nervous: dizziness; Heart Rate and Rhythm: bradycardia; Liver and Biliary: hepatitis; Metabolic and Nutritional: dehydration; Platelet, Bleeding and Clotting: thrombocytopenia; Neoplasms: lymphoma; Red Blood Cell: anemia, hemolytic anemia; Resistance Mechanism: cellulitis, sepsis, serum sickness, sarcoidosis; Respiratory: lower respiratory tract infection (including pneumonia), pleurisy, pulmonary edema; Skin and Appendages: increased sweating; Vascular (Extracardiac): thrombophlebitis; White Cell and Reticuloendothelial: leukopenia, lymphadenopathy. Adverse Reactions in Pediatric Patients: Pediatric Crohn’s Disease: There were some differences in the adverse reactions observed in the pediatric patients receiving REMICADE compared to those observed in

REMICADE® (infliximab)

REMICADE® (infliximab)

administration. Cases of myocardial ischemia/infarction and transient visual loss have also been rarely reported in association with REMICADE during or within 2 hours of infusion. Adverse Reactions in Pediatric Patients: The following serious adverse reactions have been reported in the post-marketing experience in children: infections (some fatal) including opportunistic infections and tuberculosis, infusion reactions, and hypersensitivity reactions.

Serious adverse reactions in the post-marketing experience with REMICADE in the pediatric population have also included malignancies, including hepatosplenic T-cell lymphomas [see Boxed WARNINGS and Warnings and Precautions], transient hepatic enzyme abnormalities, lupus-like syndromes, and the development of autoantibodies. DRUG INTERACTIONS: Use with Anakinra or Abatacept: An increased risk of serious infections was seen in clinical studies of other TNFα-blocking agents used in combination with anakinra or abatacept, with no added clinical benefit. Because of the nature of the adverse reactions seen with these combinations with TNF-blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNFα-blocking agents. Therefore, the combination of REMICADE and anakinra or abatacept is not recommended [see Warnings and Precautions]. Use with Tocilizumab: The use of tocilizumab in combination with biological DMARDs such as TNF antagonists, including REMICADE, should be avoided because of the possibility of increased immunosuppression and increased risk of infection. Methotrexate (MTX) and Other Concomitant Medications: Specific drug interaction studies, including interactions with MTX, have not been conducted. The majority of patients in rheumatoid arthritis or Crohn’s disease clinical studies received one or more concomitant medications. In rheumatoid arthritis, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. Concomitant Crohn’s disease medications were antibiotics, antivirals, corticosteroids, 6-MP/AZA and aminosalicylates.

In psoriatic arthritis clinical trials, concomitant medications included MTX in approximately half of the patients as well as NSAIDs, folic acid and corticosteroids. Concomitant MTX use may decrease the incidence of anti-infliximab antibody production and increase infliximab concentrations.

Immunosuppressants: Patients with Crohn’s disease who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants [see Adverse Reactions]. Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn’s disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates. Cytochrome P450 Substrates: The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as infliximab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of REMICADE in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed. USE IN SPECIFIC POPULATIONS: Pregnancy: Pregnancy Category B.: It is not known whether REMICADE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. REMICADE should be given to a pregnant woman only if clearly needed. Because infliximab does not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with REMICADE. No evidence of maternal toxicity, embryotoxicity or teratogenicity was observed in a developmental toxicity study conducted in mice using an analogous antibody that selectively inhibits the functional activity of mouse TNFα. Doses of 10 to 15 mg/kg in pharmacodynamic animal models with the anti-TNF analogous antibody produced maximal pharmacologic effectiveness. Doses up to 40 mg/kg were shown to produce no adverse effects in animal reproduction studies. As with other IgG antibodies, REMICADE crosses the placenta and has been detected up to 6 months in the serum of infants born to female patients treated with REMICADE during pregnancy. Consequently, these infants may be at increased risk of infection, and caution is advised in the administration of live vaccines to these infants [see Warnings and Precautions]. Nursing Mothers: It is not known whether REMICADE is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for adverse reactions in nursing infants from REMICADE, women should not breast-feed their infants while taking REMICADE. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: The safety and effectiveness of REMICADE have been established in pediatric patients 6 to 17 years of age for induction and maintenance treatment of Crohn’s disease or ulcerative colitis. However, REMICADE has not been studied in children with Crohn’s disease or ulcerative colitis <6 years of age. Pediatric Crohn’s Disease: REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy [see Boxed Warnings, Warnings and Precautions, Indications and Usage (1.2) in full Prescribing Information, Dosage and Administration (2.2) in full Prescribing Information, Clinical Studies (14.2) in full Prescribing Information, and Adverse Reactions]. REMICADE has been studied only in combination with conventional immunosuppressive therapy in pediatric Crohn’s disease. The longer term (greater than 1 year) safety and effectiveness of REMICADE in pediatric Crohn’s disease patients have not been established in clinical trials. Pediatric

Ulcerative Colitis: The safety and effectiveness of REMICADE for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy are supported by evidence from adequate and well-controlled studies of REMICADE in adults. Additional safety and pharmacokinetic data were collected in 60 pediatric patients aged 6 years and older [see Clinical Pharmacology (12.3) in full Prescribing Information, Dosage and Administration (2.4) in full Prescribing Information, Adverse Reactions, and Clinical Studies, (14.4) in full Prescribing Information]. The effectiveness of REMICADE in inducing and maintaining mucosal healing could not be established. Although 41 patients had a Mayo endoscopy subscore of 0 or 1 at the Week 8 endoscopy, the induction phase was open-label and lacked a control group. Only 9 patients had an optional endoscopy at Week 54. In the pediatric UC trial, approximately half of the patients were on concomitant immunomodulators (AZA, 6-MP, MTX) at study start. Due to the risk of HSTCL, a careful risk-benefit assessment should be made when REMICADE is used in combination with other immunosuppressants.

The longer term (greater than 1 year) safety and effectiveness of REMICADE in pediatric ulcerative colitis patients have not been established in clinical trials.

Juvenile Rheumatoid Arthritis (JRA): The safety and efficacy of REMICADE in patients with juvenile rheumatoid arthritis (JRA) were evaluated in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension, for a maximum of 44 weeks. Patients with active JRA between the ages of 4 and 17 years who had been treated with MTX for at least 3 months were enrolled. Concurrent use of folic acid, oral corticosteroids (≤ 0.2 mg/kg/day of prednisone or equivalent), NSAIDs, and/or disease modifying antirheumatic drugs (DMARDs) was permitted. Doses of 3 mg/kg REMICADE or placebo were administered intravenously at Weeks 0, 2 and 6. Patients randomized to placebo crossed-over to receive 6 mg/kg REMICADE at Weeks 14, 16, and 20, and then every 8 weeks through Week 44. Patients who completed the study continued to receive open-label treatment with REMICADE for up to 2 years in a companion extension study. The study failed to establish the efficacy of REMICADE in the treatment of JRA. Key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults. Additionally, a higher rate of clearance of infliximab was observed than had been observed in adults [see Clinical Pharmacology (12.3) in full Prescribing Information]. A total of 60 patients with JRA were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. The proportion of patients with infusion reactions who received 3 mg/kg REMICADE was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks. The most common infusion reactions reported were vomiting, fever, headache, and hypotension.

In the 3 mg/kg REMICADE group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions). In the 6 mg/kg REMICADE group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction.

Two of the 6 patients who experienced serious infusion reactions received REMICADE by rapid infusion (duration of less than 2 hours). Antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg REMICADE compared with 12% (6/49) of patients who received 6 mg/kg. A total of 68% (41/60) of patients who received 3 mg/kg REMICADE in combination with MTX experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg REMICADE in combination with MTX over 38 weeks. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia. Other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient. Geriatric Use: In rheumatoid arthritis and plaque psoriasis clinical trials, no overall differences were observed in effectiveness or safety in 181 patients with rheumatoid arthritis and 75 patients with plaque psoriasis, aged 65 or older who received REMICADE, compared to younger patients—although the incidence of serious adverse reactions in patients aged 65 or older was higher in both REMICADE and control groups compared to younger patients. In Crohn’s disease, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis studies, there were insufficient numbers of patients aged 65 and over to determine whether they respond differently from patients aged 18 to 65. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly [see Adverse Reactions]. OVERDOSAGE: Single doses up to 20 mg/kg have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately. REFERENCES: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-S247. 2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044 U.S. License No. 1864 Janssen Biotech, Inc. 2011 Revised October 2011 25R11047A

life

LC

Never one to shy away from a challenge, the famed actress and author isn’t afraid to tackle the sensitive subject of digestive distress.

By Jessie Sholl of Everyday Health

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© Katy Winn/Corbis

my J

t

Gastro Health

o say that Jamie Lee Curtis has led a varied life would be a bit of an understatement. Early in her career as an actress, she stepped out from behind the shadow of her famous parents (Janet Leigh, best known for her role in the Alfred Hitchcock classic Psycho, and Tony Curtis, beloved for his work in Some Like It Hot and Spartacus) to earn the reputation of a “scream queen” for her roles in the horror films Halloween and Prom Night.

Curtis went on to achieve success as a comedic actress in Trading Places and A Fish Called Wanda, and she won a Golden Globe for her starring role in True Lies. She can be seen on the big screen this fall in the family film Beverly Hills Chihuahua. Married to Christopher Guest, the writer, director, and actor, Curtis is the mother of two young children and is also a successful children’s author, with her eighth book due out in September.

Long praised as one of the most beautiful women in Hollywood, Curtis caused a stir in 2002 when she appeared in the pages of More magazine wearing no makeup and a less-than-flattering pair of shorts for a piece lampooning the film industry’s superficial notions of beauty. And in her newest role, the 49-year-old proves that she’s not afraid to tackle a subject that might make some squeamish: digestive health.

Everyday Health: You took a big risk in 2002 in More magazine’s article, “True Thighs,” in which you appeared in photographs without any makeup and wearing unflattering bicycle shorts. What was that like, and how did it affect your life afterward?

JLC

: The More magazine photo shoot allowed me to talk about the myths of women’s bodies and the conspiracy among advertisers, the media, and the

beauty industry to keep women searching for ways to make themselves more like the models they see.

The subsequent media firestorm and then the following ad campaigns, such as Dove’s Natural Beauty campaign, have given voice to the real needs of women, and I am proud to have been a torchbearer in the struggle for all women’s selfhood.

Everyday Health: You’ve written seven children’s books, including Today I Feel Silly & Other Moods That Make My Day, and you’ve got a new one coming out in September. Can you tell us a little about the transition from actress to writer?

JLC

: As an actress, I am merely interpreting someone else’s ideas and words. Being a writer allows me my own voice, which is so gratifying. Also, I’ve been writing for 17 years, so it hasn’t been a quick transition.

Everyday Health: Does your writing of children’s books affect your relationship with your own kids?

Have your kids helped you with the ideas or the execution of your books?

JLC

: My children are my muses. [The ideas for] four of my books came directly from them; two came from other children. I hope they feel pride in being the catalyst for these lovely books.

JLC

: Almost half of Americans have some day-to-day problems with digestion — some minor and some profound.

And although the New York Times recently had an article saying that our childhood obesity rates may have hit a plateau, still, if you look around, we are the fattest people on the planet, so we’re clearly going to be the people with the most digestive problems. Also, everything has its time... You know, five years ago we barely understood the words “global warming,” and now the words “carbon footprint” are being discussed at every company meeting. People are finally paying attention — doing things like driving less and dumping their gas-guzzling cars. In the same way, digestive problems are on the rise and are reaching their “time,” if you will. I think the fact that the World Gastroenterology Organization (WGO) has published guidelines to help people improve their digestive health shows how serious digestive problems are and that more people are paying attention to their digestive systems.

JLC

Everyday Health: What do you do to maintain your own digestive health?

JLC

: I eat a lot of raw veggies as well as protein, and I avoid lots of carbs.

Everyday Health: What are some other ways people can keep their digestive systems running smoothly? : Here are my guidelines — I call them my ten F-words: • Eat frequent small meals.

• Increase your fiber intake, by eating fruits, vegetables, and legumes.

• Try to eat three to five servings of fish a week.

• Avoid fried and fatty foods. That’s obvious.

• Consume fermented foods like yogurt.

• Consume meats that are lower in fat — try chicken, turkey, and pork.

• Fluids are key. Drink lots of water!

• Slow down when you’re eating and chew food properly, to encourage a “full” feeling.

• Stay fit. Exercise regularly.

• Maintain a fighting weight.

What I mean by “fighting weight” is that whenever you see a fighter, he’s at the perfect weight, lean and strong. Remember [the movie] Raging Bull? When [the boxer] Jake LaMotta was about to go in the ring, he was in perfect shape, but then after the fight he gained all that weight. I think the same can be said here. You want to stay at a fighting weight — you want to stay in the kind of shape you’d be in if you were fighting for your life, because we are.

JLC Here are my guidelines — I call them my ten F-words:

The problem is that people take life for granted, as if life’s always going to be here and they can eat and drink and sloth their way through life and that it’s all fine. And that’s not true. We have to earn our good health. Good health does not just show up at your door.

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Copyright 2011 EverydayHealth.com. Reprinted with permission.

Everyday Health: You recently appeared in commercials for Activia yogurt. Do you think the stigma of talking about digestive problems has lessened, or do you think there’s more discussion because more people are suffering from digestive disorders now?

Gastro Health

Evaluation of Swallowing “Doctor, I have trouble swallowing.”

Francisco J. Baigorri, MD Assistant Professor of Clinical Medicine FIU College of Medicine Dysphagia is the medical term used to describe difficulty swallowing. The esophagus is a muscular tube that connects your throat to your stomach. With each swallow, the esophageal muscle contracts and pushes food into the stomach. At the lower end of the esophagus, a valve (a special sphincter muscle) remains closed except when food or liquid is swallowed or when you belch or vomit.

Acid reflux disease is the most common cause of dysphagia.

People with acid reflux may have problems in the esophagus, such as an ulcer, a stricture (narrowing of the esophagus), or less likely a cancer causing difficulty swallowing. Strong anti-acids, such as omeprazole, lansoprazole, pantoprazole among others, are frequently used to treat this condition.

Another cause of dysphagia is Eosinophilic Esophagitis (EE), which is more common in young adults. The symptoms are similar to those of gastroesophageal reflux disease (GERD). Eosinophilic Esophagitis is an allergic inflammatory condition of the esophagus.

The condition is not well understood, but food allergies may play a significant role. An endoscopy with biopsies of the esophagus is needed to confirm the diagnosis, and the treatment is primarily steroids like the ones used to treat asthma.

Dysphagia can also be caused by neurologic problems, or problems with the nerves that help us swallow. Damage to the brain or different nerves may leave the mouth, tongue, or throat muscles weak or with poor coordination. Food entering the larynx can cause choking, coughing, or even lead to a type of pneumonia called aspiration pneumonia. Some patients need to be fed via a special tube (PEG) that goes directly into the stomach to prevent aspiration.

Another cause of dysphagia, although much less common is achalasia. Achalasia is a disease that affects the way the esophageal muscle contracts and pushes food into the stomach with each swallow. Most achalasia patients are symptomatic for years before seeking medical attention. The most common symptoms are dysphagia for solids and liquids, regurgitation, and chest pain. Upper endoscopy with dilation or even surgery is needed in most patients with this disease.

Patients that have an esophageal ring (Shatzki’s ring) or a stricture as the cause of their dysphagia have problems associated with swallowing that usually result in an intense feeling of discomfort as a swallowed food bolus slowly moves down the esophagus. Occasionally, they can result in food becoming stuck in the esophagus – which is known as food impaction. Most of the time, an urgent endoscopy is required to remove the food bolus.

For evaluation of dysphagia, your doctor will perform a physical examination and use a variety of tests to determine the cause of your swallowing problem. These tests could include a barium swallow x-ray, an upper endoscopy (EGD), or an esophageal muscle test (manometry). Upper endoscopy lets your doctor examine the lining of the upper part of your gastrointestinal tract, which includes the esophagus, stomach and duodenum. If there’s a narrowing in the esophagus, the doctor can stretch (dilate) the area with a special instrument.

Trouble swallowing always requires medical attention. Make sure you contact your gastroenterologist to be evaluated and treated appropriately if you develop difficulty swallowing.

This information is intended only to provide general guidance. It does not provide definitive medical advice. It is very important that you consult your doctor about your specific condition.

Gastro Health

GERD

The word is

Alfredo Rabassa, MD Board Certified Gastroenterologist

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder in the United States occurring monthly, weekly and daily in 45%, 25% and 7% of the population, respectively. Gastroesophageal reflux occurs when the contents of the stomach back up into the esophagus and throat. GERD occurs when individuals with reflux develop symptoms or injury to the esophagus.

Treatments

Symptoms Common symptoms of GERD include heartburn and regurgitation of food into the esophagus and throat. Less common symptoms include upper abdominal pain, chronic cough, hoarseness, chest pain, sensation of a “ball” in the throat, asthma, sore throat, chronic sinus infections, vomiting and difficulty or painful swallowing. Worrisome signs and symptoms include unexplained weight loss, anemia, loss of appetite and bleeding (vomiting blood or black tarry stools).

Diagnosing

GERD is usually diagnosed based on symptoms and response to treatment. A trial of lifestyle changes and a short course of over-the-counter (OTC) medication is often recommended for individuals with mild symptoms of acid reflux with no evidence of complications. Further testing may be indicated when symptoms fail to improve, if the diagnosis is uncertain or if an individual develops worrisome signs and symptoms.

Endoscopy is commonly used to evaluate patients with GERD symptoms. After sedation is administered, a small flexible tube with a camera known as an endoscope is passed into the mouth, tubular esophagus, stomach and the first part of the small intestine. The image is projected onto a monitor permitting detailed visualization of the gastrointestinal tract’s surface. During the procedure, specimens of the lining of the intestinal tract can be obtained to determine the extent of damage and to establish the diagnosis of certain diseases such as infections or tumors. Specialized instruments passed through the endoscope during the procedure

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allow diagnostic evaluation and therapeutic intervention. Dedicated endoscopes, such as the endoscopic ultrasound, permit the physician to determine the extent of tumor involvement and, in the case of early detection, perform complete endoscopic removal.

A 48-hour esophageal pH study is the most direct way to confirm the diagnosis of acid reflux. The test involves placement of a small capsule in the esophagus at the time of endoscopy. This capsule contains a pH-sensor which measures esophageal acid exposure during a 48-hour period that can be analyzed to confirm or exclude the diagnosis of acid reflux when the diagnosis of acid reflux is unclear.

Esophageal manometry involves swallowing a small tube that measures esophageal muscle contractions. This procedure can identify abnormal motility patterns of the esophagus and determine if the lower esophageal sphincter, which acts as a barrier to acid reflux, is functioning properly. In a similar manner, esophageal impedance is a procedure that can help determine if non-acid reflux may be responsible for the patient’s symptoms.

Complications of acid reflux include ulcers, strictures, lung disease, throat problems, and the precancerous condition know as Barrett’s esophagus. Barrett’s esophagus is found in 10% of patients with GERD. Periodic endoscopy is performed to monitor patients with Barrett’s esophagus. The most feared complication of GERD is the development of esophageal cancer, often seen in patients with underlying Barrett’s esophagus.

Treatment consists of lifestyle modifications such as weight loss, elevating the head of the bed, cessation of smoking, replacing tight clothing, eliminating foods which induce reflux, and also avoiding large, fatty and late meals.

Many patients may require over-the-counter antacids such as Maalox, Mylanta and Tums, while others may obtain relief with drugs which decrease acid production known as histamine-2 receptor antagonists such as ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid) and cimetidine (Tagamet). The more effective acid decreasing medications know as Proton Pump Inhibitors (PPI) include omeprazole (Prilosec, Zegerid), lanzoprazole (Prevacid), rabeprazole (Aciphex), pantaprazole (Protonix), esomeprazole (Nexium) and dexlanzoprazole (Dexilant). Some of the PPI formulations are available over-thecounter and are most effective if taken 30-60 minutes before breakfast.

Surgery is reserved for the rare patient who may not be able to take medications or has developed significant regurgitation despite lifestyle modifications. The most commonly performed procedure is the Nissen fundoplication. Although effective in a select group of patients, this procedure is associated with troublesome and often non-reversible post-operative symptoms such as abdominal bloating and gas, early satiety, diarrhea as well as surgical complications. In some studies, up to 65% of patients continue to require further acid reducing therapy despite successful surgery. Newer endoscopic approaches to the management of GERD are being developed for this group of patients.

PHYSICIAN DIRECTORY Gastro Health is a medical group made up of the finest physicians and allied health professionals in South Florida specializing in the treatment of gastrointestinal disorders, nutrition, and digestive health.

Our team of board-certified physicians, physician assistants, nurse practitioners, nutritionists and technicians combine their clinical expertise and experience to provide patients with quality medical and preventive care in the field of Gastroenterology.

With office locations, endoscopy centers, and affiliations with South Florida’s premier hospitals, there is always a Gastro Health physician minutes away from home.

GASTRO HEALTH MAGAZINE • 2012

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PHYSICIAN DIRECTORY Francisco J. Baigorri, MD * Gastroenterologist Care Center 1

Simon Behar, MD * Gastroenterologist Care Center 3

Barry E. Brand, MD Gastroenterologist Care Center 2

Gustavo Calleja, MD * Gastroenterologist Care Center 1

Marc S. Carp, MD Gastroenterologist Care Center 6

John P. Christie, MD Colorectal Surgeon Care Center 1

Lewis R. Felder, MD Gastroenterologist Care Center 7

Jose P. Ferrer, Jr., MD * Gastroenterologist Care Center 3

Jose P. Ferrer, Sr., MD * Gastroenterologist Care Center 3

Nelson Garcia Jr. MD * Gastroenterologist Care Center 8

Daniel Gelrud, MD * Gastroenterologist Care Center 1

Harris I. Goldberg, MD Gastroenterologist Care Center 1

Guillermo Gubbins, MD * Gastroenterologist Care Center 10

Eugenio J. Hernandez, MD * Gastroenterologist Care Center 3

Moises E. Hernandez, MD * Gastroenterologist Care Center 3

Richard E. Hernandez, MD * Gastroenterologist Care Center 5

Eduardo Krajewski, MD * Colorectal Surgeon Care Center 9

Robert C. Lanoff, MD * Gastroenterologist Care Center 2

Jose A. Lavergne, MD * Gastroenterologist Care Center 7

James S. Leavitt, MD Gastroenterologist Care Center 1

* Habla EspaĂąol

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GASTRO HEALTH MAGAZINE â&#x20AC;˘ 2012

Gastro Health

Marc Lederhandler, MD Gastroenterologist Care Center 1

Jerry Martel, MD, MPH * Gastroenterologist Care Center 8

Antonio Martinez, MD Pathologist Director Pathology Laboratory

Flavia Mendes, MD * Gastroenterologist Care Center 1

Pedro Morales, MD * Gastroenterologist Care Center 8

Brett R. Neustater, MD Gastroenterologist Care Center 7

Javier L. Parra, MD * Gastroenterologist Care Center 1

Alfredo Rabassa, MD * Gastroenterologist Care Center 1

Ricardo J. Roman, MD * Gastroenterologist Care Center 7

Seth D. Rosen, MD Gastroenterologist Care Center 2

Neil E. Rosenkranz, MD Gastroenterologist Care Center 2

S. Lawrence Rothman, MD Gastroenterologist Care Center 1

Eduardo Ruan, MD * Gastroenterologist Care Center 1

Andrew I. Sable, MD Gastroenterologist Care Center 2

Howard I. Schwartz, MD Gastroenterologist Care Center 1

Daniel Seckinger, MD Radiologist Imaging Director

David A. Sommer, MD Gastroenterologist Care Center 2

Marcos Szomstein, MD * Colorectal Surgeon Care Center 9

Stefania L. Vernace, MD Gastroenterologist Care Center 1

Arie Slomianski, MD * Gastroenterologist Care Center 1

* Habla Espa単ol

Gastro Health

Allied Healthcare Staff

22 ::

* Habla Español

Darlene Boytell-Perez, ARNP *

Sabrina Kaplan, PA-C*

Rebecca Karousatos, MS, RD, LDN

Ellen Matas-Sosa, PA-C

Hernando Mispireta, ARNP *

Rachael Robinson, RN

Hengameh Shahidpoor, ARNP

Kayce Tugg, MSN, RN

Care Centers

Insurances

Care Center 1 Main Office 7500 SW 87 Avenue, Suite 200 Miami, FL 33173 305-913-0666

Care Center 7 Satellite Office #1 5803 NW 151 Street, Suite 105 Miami Lakes, FL 33014 305-770-0062

Care Center 1 Satellite Office 6141 Sunset Drive, Suite 301 Miami, FL 33143 305-913-0666

Care Center 7 Satellite Office #2 21110 Biscayne Boulevard, Suite 206 Aventura, FL 33180 305-770-0062

Care Center 2 9555 N. Kendall Drive, Suite 100 Miami, FL 33176 305-273-7319

Care Center 8 8200 SW 117 Avenue, Suite 110 Miami, FL 33183 305-274-5500

Care Center 3 8950 N. Kendall Drive, Suite 306-W Miami, FL 33176 305-596-9966

Care Center 9 7765 SW 87 Avenue, Suite 212 Miami, FL 33173 305-596-3080

Care Center 4 9655 SW 162 Avenue, Suite 205 Miami, FL 33196 305-468-4191

Care Center 10 5000 University Drive, Suite 3370 Coral Gables, FL 33146 305-662-6170

Care Center 5 7765 SW 87 Avenue, Suite 105 Miami, FL 33173 305-274-0808

Imaging Center 7500 SW 87 Avenue, Suite 200-A Miami, FL 33173 305-468-4190

Care Center 6 1400 NE Miami Gardens Drive; Suite 221 North Miami Beach, FL 33179 305-949-2020

Infusion Center 7500 SW 87 Avenue, Suite 200-A Miami, FL 33173 305-913-0660

AARP Medicare Complete Aetna American Heritage Life Insurance American Medical Security AvMed Baptist Executive Health Beechstreet Blue Cross Blue Shield Cigna Coventry Health Care Dimensions Health First Health Network Humana Humana Champus Tricare Mail Handlers Benefit Plans Medica Health Plan Medicare Part B MultiPlan Neighborhood Health Plan OneSource Preferred Care Partners United Healthcare VISTA Health Plans

Care Center 7 Main Office 16855 NE 2nd Avenue, Suite 202 North Miami Beach, FL 33162 305-770-0062

Pathology Laboratory 9000 SW 87 Court, Suite 110 Miami, FL 33176 305-468-4194

GASTRO HEALTH MAGAZINE • 2012

You're 50...

Happy Birthday!

It's time for your first colon cancer screening

www.gastrohealth.com

Pediatric News

Gastro Health

Spit

Happens

Ruben Gonzalez-Vallina, MD, FAAP Board Certified Pediatric Gastroenterologist

Gastroesophageal Reflux in Pediatrics Gastroesophageal reflux (GER), defined as passage of gastric contents into the esophagus, and GER disease (GERD), defined as symptoms or complications of GER, are common pediatric problems encountered by both primary and specialty medical providers. Clinical manifestations of GERD in children include vomiting, poor weight gain, dysphasia, abdominal or substantial pain, esophagitis, and respiratory disorders.

Reflux and your baby (0-24 month olds) Gastroesophageal reflux (GER) occurs during or after a meal when stomach contents go back into the tube that connects the mouth to the stomach. GER occurs often in normal infants. Most infants with GER are happy and healthy even though they spit up or vomit. Spitting up tends to peak at four months and most infants stop spitting up by 12 months of age.

If your baby is spitting up without discomfort and is making appropriate weight gains, then he or she is probably a normal spitter.

Worrisome symptoms of reflux disease in infants (0-24 months old)

Diagnosis

Treatment

Is made usually by history, but there are tests that can be done in severe cases, such as: • Barium swallow or upper GI series.

This is a special x-ray test that uses barium to highlight the esophagus, stomach, and upper part of the small intestine.

• PH probe. Measures levels of stomach acids.

It also helps determine if breathing problems are the result of reflux.

• Upper GI endoscopy. This is done using an endoscope (a thin, flexible, lighted tube and camera) that allows the doctor to look directly inside the esophagus, stomach, and upper part of the small intestine.

For infants: • Elevating the head of the baby’s crib or bassinet • Holding the baby upright for 30 minutes after the feeding • Thickening bottle feedings with cereal (do not do this without a doctor’s supervision) • Changing feeding schedule • Trying solid food (with your doctor’s approval)

1. Vomiting associated with • Blood • Green or yellow fluid • Poor weight gain 2. Inconsolable or severe crying and irritability 3. Persistent food refusal • Poor growth or failure to thrive • Difficulty eating 4. Breathing problems • Difficulty breathing • Repeat bouts of pneumonia • Breathing stops • Turning blue • Chronic cough • Wheezing If you have concerns, speak to your health care provider.

Most babies outgrow reflux by one year of age.

For older children: • Elevating the head of the child’s bed • Keeping the child upright for at least two hours after eating • Serving several small meals throughout the day, rather than three large meals • Limiting foods and beverages that seem to worsen the child’s reflux • Encouraging your child to get regular exercise

If the reflux is severe or does not get better, your doctor may recommend drugs to treat it.

Drugs to Lessen Gas: Mylicon, Gaviscon Drugs to Neutralize or Decrease Stomach Acid: Antacids such as Mylanta and Maalox, Histamine-2(H2) blockers such as Axid, Pepcid, Tagament, or Zantac, Proton-pump inhibitors such as Nexium, Prilosec, Prevacid, Aciphex, and Protonix.

Gastro Health

Surgical Treatments for

Colon Cancer

Colon cancer affects over 100,000 men and women each year. The available treatment options that have proven to be effective for colon cancer are surgery and chemotherapy. A combination of these treatments is common to achieve better results. But usually, surgery is the most effective option to treat colon cancer.

The surgical removal of a malignant tumor offers the best chance for a cure. This is especially true if the cancer has not spread to other areas of the body. Surgery is used to cure the disease when it is confined to one single area and also in other cases for diagnosis and relief of ongoing symptoms. Surgery is also used to determine the staging of the cancerous tumor. The surgical specimen is sent to a pathology lab where it is checked under a microscope to assess the depth of the tumor and the possible spread to surrounding lymph nodes.

If surgery is needed to treat colon cancer, there are 3 different modalities that are being used at this time. The oldest procedure for treating colon cancer is known as open surgery, in which the surgeon removes a part of the colon through a big cut in the abdomen. This kind of procedure is usually more painful and requires a longer hospital stay and recovery period before going back to work.

Over the last 20 years, a minimally invasive approach has developed called laparoscopic surgery. Larger facilities and advanced centers have this option available. In this procedure, the surgeon makes three to four small incisions in the abdomen. A long and skinny camera that is hooked to a television monitor enters the body and the surgeon is able to see the inside of the abdominal cavity on the monitor. Through the other incisions, the surgeon will remove the cancerous part of the colon. How much colon has to be removed depends on surgical principles and the size of the tumor. After

Marcos Szomstein, MD, FACS, FASCRS Board Certified Colorectal Surgeon

the surgery, which usually takes 1-2 hours to perform, the patient has to stay in the hospital for 2-3 days. Patients that have laparoscopic procedures experience less postoperative pain, can return to their normal activities in 1-2 weeks, and can eat sooner. A better cosmetic result is another advantage.

Laparoscopic colon cancer surgery has been proven to be just as effective at removing colon cancer as the open technique. But not every patient is a candidate for laparoscopic surgery, although a majority is. With the common goal of a patientâ&#x20AC;&#x2122;s safety in mind, the surgeon will make the decision either before or during surgery regarding which approach is better for an individual patient based on different factors.

There is a third option which is still in its infancy called robotic surgery.

This technique uses a machine with robotic arms that work inside the patientâ&#x20AC;&#x2122;s abdomen guided by a surgeon who is present in the operating room but sitting at an operating console. It has a 3D magnifying camera that allows the surgeon to have a great view of the operative field while he controls the robotic arms remotely. It is very similar to laparoscopic surgery in many aspects including recovery time, postoperative pain and probably surgical results. This procedure has been used in clinical practice but does take longer than laparoscopic surgery without any clear clinical benefits.

Time will determine its role in colon cancer surgery.

The most important factor to have a successful outcome when having surgery for colon cancer is to choose the right surgeon to perform the procedure. It has been proven that surgeons who specialize in colon surgery and have a high volume of cases have better results than surgeons who are not as familiar with surgery for colon cancer. Patients should take their time and ask all the necessary questions to find a surgeon well trained and with enough experience to handle these cases in order to achieve optimal results.

GASTRO HEALTH MAGAZINE â&#x20AC;˘ 2012

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Gastro Health

Inflammatory Bowel Disease: Time to Step Down?

The two major types of inflammatory bowel disease (IBD) are ulcerative colitis and Crohn’s disease.

Ulcerative colitis is limited to the colon or large intestine.

Crohn’s disease, on the other hand, may involve any part of the gastrointestinal tract from the mouth to the anus. Most commonly, it affects the small intestine, the colon, or both. In one of the largest studies (based upon 9 million health insurance claims), the prevalence of Crohn’s disease and ulcerative colitis in adults was 201 and 238 per 100,000 population, respectively.

Brett Neustater, MD Board Certified Gastroenterologist Aside from the annoyance and possible disabling symptoms which can accompany these diseases including abdominal pain, diarrhea, and GI bleeding, IBD also has the potential to run a severe course leading to hospitalization, surgery, and a markedly diminished quality-of-life.

This is especially true for Crohn’s disease which, although unable to be cured by surgery, leads to at least one surgery in 75% of patients affected. One challenge that has plagued physicians and patients alike has been that this high surgical rate has not declined despite the more widespread use of more aggressive therapy in order to induce and maintain remission. This has led IBD specialists to re-think the standard algorithms employed in the treatment of inflammatory bowel disease, especially Crohn’s disease.

Traditionally, doctors have taken a stepwise approach to the use of medications for inflammatory bowel disease referred to as a “step up therapy.” With this approach, initially the more benign drugs or drugs are given for a short period. If they fail to provide relief, drugs from a higher step are then used.

Treatment typically begins with aminosalicylates, which are aspirinlike anti-inflammatory drugs such as mesalamine (Asacol, Lialda, Pentasa and Apriso). These drugs can be taken orally or administered as a rectal suppository or enema. They are often very effective in both inducing and maintaining remission in ulcerative colitis, although their value in Crohn’s disease, especially for maintaining remission, is less clear.

If the aminosalicylates don’t provide adequate relief, the doctor will usually prescribe a corticosteroid, which is a rapid-acting anti-inflammatory agent that can provide rapid relief of symptoms as well as a significant decrease in inflammation. However, because of side-effects associated with their long-term use, corticosteroids are used only to treat flare-ups and are not used for maintaining remission.

It is only when these drugs fail that doctors historically moved on to more aggressive therapy in terms of immune modifying agents (immunomodulators) or the newest class of medications called “Biologics.”

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GASTRO HEALTH MAGAZINE • 2012

The immunomodulators include medication such as 6-mercaptopurine, azathioprine, and methotrexate. These medications cannot be used in acute flare-ups because they may take as long as two to three months to take action.

Over the past several years, however, studies have suggested that being more aggressive with medical therapy earlier in the course of these diseases, especially Crohn’s disease, may lead to a “disease modifying effect.” Early medical intervention may lead to a more benign long-term course and also possibly obviate the need for surgery in many patients who otherwise would have had at least one, if not multiple, surgeries. The most compelling data seems to be that associated with the use of the newer Biologic class of medication either alone or in combination with an immunomodulator. This data has piqued interest in possibly reversing the traditional “step up therapy” into a new “step down approach” where more potent medications are used earlier in the disease course.

The most widely used Biologics currently consist of three medications which are also referred to as anti-TNF agents. Infliximab (Remicade) was the first to be approved by the FDA and, at the time of this writing, the only one approved for ulcerative colitis (although approval of another is expected very soon). Other anti-TNF agents approved for Crohn’s disease are Humira (adalumimab) and Cimzia (certolizumab). Remicade has the longest track record but must be administered intravenously.

The other two can be administered via subcutaneous injection, but currently there is no available oral medication of this class. There are various advantages and disadvantages of each of these medications with the decision regarding which to use in a particular patient best based upon an individual patient’s disease and symptoms.

For patients with persistent or severe symptoms despite the above therapy, other available options include more aggressive immunosuppressant agents, enrollment in clinical trials, or surgery.

Regardless of the treatment chosen, it is important that the therapy be personalized and tailored to each patient via an ongoing dialogue between the patient and his or her IBD specialist.

Working

Hand in Hand FIU College of Medicine and Gastro Health Partner up in Education In 2009 Florida International University opened the new Herbert Wertheim College of Medicine, the first public medical school in South Florida, with an initial class of 43 students. Two years before the first class started, the dean of the new medical school approached Gastro Health to form a partnership to develop the Gastroenterology curriculum. Dr. Daniel Gelrud of Gastro Health was named director of the Gastrointestinal System and Nutrition course.

With the leadership of Dr. Gelrud, doctors from Gastro Health have developed the curriculum of what the new young doctors will learn about gastrointestinal diseases. The doctors from Gastro Health give lectures and participate in innovative case conferences that help students learn basic Gastroenterology as well as the latest advances in the field.

Medical Students from FIU participate through hospital rotations with Gastro Health doctors at South Miami and Baptist Hospitals, as well as their Galloway Medical Park office located at 7500 SW 87th Avenue.

The students are exposed to the latest advances and new technologies mastered by these doctors.

Several Gastro Health physicians come from academic backgrounds.

Dr. Javier Parra taught medical students and Gastroenterology fellows advanced endoscopic procedures including ERCP (Endoscopic Retrograde Cholangiopancreatography) and Enteroscopy at the University of Miami. Dr. Flavia Mendes was also a professor from the University of Miami with expertise in Hepatology before joining the practice. Dr. Daniel Gelrud was an assistant professor at the Albert Einstein College of Medicine in New York.

Gastro Health is a comprehensive gastroenterology group whose physicians have expertise in many areas. FIU medical students benefit from that experience. Dr. Rothman and Dr. Mendes have special interest in liver disease. Students learn about Ulcerative colitis and Crohnâ&#x20AC;&#x2122;s disease from Dr. Schwartz and Dr. Leavitt. Biliary disease and complications of liver disease is taught by Dr. E. Hernandez and Dr. Leavitt.

Dr. Rabassa introduces the students to important common conditions such as ulcer and reflux disease. Dr. Ruan explores the causes of diarrhea and constipation. Dr. Calleja tackles the common and important irritable bowel syndrome (IBS), while Dr. Baigorri digs into the complex issue of the obesity epidemic in the United States.

The association between the FIU School of Medicine and Gastro Health proves the commitment of providing academic level state-ofthe-art care to patients. This academic environment is conducive to the practice of excellent medicine that not only benefits patients, but also the future medical doctors who rotate through Gastro Healthâ&#x20AC;&#x2122;s facilities.

Course Director Daniel Gelrud, MD Teaching Faculty Francisco J. Baigorri, MD Gustavo Calleja, MD Eugenio Hernandez, MD James Leavitt, MD Marc Leaderhandler, MD Flavia Mendes, MD Javier Parra, MD Alfredo Rabassa, MD Lawrence Rothman, MD Eduardo Ruan, MD Howard Schwartz, MD Stefania Vernace, MD Nutrition Faculty Diana Bell Rebecca Karousatos

Maintain remission in the comfort of home...

…wherever home may be at the moment.

• In a maintenance trial, of the patients who achieved clinical response at week 4, greater proportions of HUMIRA-treated patients, compared to placebo patients, were in clinical remission at week 26 (40% vs 17%, P<0.001) and week 56 (36% vs 12%, P<0.001)1 • HUMIRA can be self-injected at home or almost anywhere, after a physician determines that it is appropriate and after proper training in injection technique. Instruct patients to refer to storage instructions found in the Medication Guide1 1

Indications

HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

1

Safety Considerations Serious Infections

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Malignancies

Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.

Other Serious Adverse Reactions

Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.

IMPORTANT SAFETY INFORMATION1

SERIOUS INFECTIONS Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

HUMIRA should be discontinued if a patient develops a serious infection or sepsis.

Reported infections include: • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before HUMIRA use and during therapy. Treatment for latent TB should be initiated prior to HUMIRA use.

• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

• Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with HUMIRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

• Do not start HUMIRA in patients with an active infection, including localized infections.

• Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.

• Exercise caution in patients with chronic or recurrent infection or with underlying conditions which may predispose them to infection, patients who have been exposed to TB, patients with a history of opportunistic infection, or patients who have resided or traveled in regions where TB or mycoses are endemic.

• Patients who develop a new infection should undergo a prompt and complete diagnostic workup, and appropriate antimicrobial therapy should be initiated.

• Drug interactions with biologic products: Concurrent use of anakinra or abatacept with HUMIRA is not recommended, as the combination of anakinra or abatacept with TNF blockers has been associated with an increased risk of serious infections. This risk has also been observed with rheumatoid arthritis patients treated with rituximab who received subsequent treatment with a TNF blocker.

MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases has occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

• The risks and benefits of HUMIRA treatment should be considered prior to initiating or continuing therapy in a patient with known malignancy.

• More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials.

• Non-melanoma skin cancer (NMSC) has been reported during clinical trials for HUMIRA-treated patients. All patients, particularly those with history of prolonged immunosuppressant or PUVA therapy, should be examined for the presence of NMSC prior to and during treatment with HUMIRA. • In HUMIRA clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.

• Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use.

• Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.

HYPERSENSITIVITY • Anaphylaxis and angioneurotic edema have been reported rarely following HUMIRA administration.

• If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.

HEPATITIS B VIRUS REACTIVATION • Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.

• Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating TNF blocker therapy.

• Exercise caution in patients who are carriers of HBV and monitor them during and after treatment with HUMIRA. • Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation.

• Exercise caution when considering resumption of HUMIRA therapy after appropriate treatment for HBV. NEUROLOGIC REACTIONS • TNF blockers, including HUMIRA, have been associated in rare cases with new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.

• Exercise caution when considering HUMIRA for patients with these disorders.

HEMATOLOGIC REACTIONS • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g. thrombocytopenia, leukopenia) has been infrequently reported with HUMIRA. • Consider stopping HUMIRA in patients with significant hematologic abnormalities.

CONGESTIVE HEART FAILURE • Worsening or new onset congestive heart failure (CHF) may occur.

• Exercise caution in patients with CHF and monitor them carefully.

AUTOIMMUNITY • Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome.

• Discontinue treatment if symptoms of a lupus-like syndrome develop.

IMMUNIZATIONS • Patients on HUMIRA should not receive live vaccines.

• It is recommended that juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HUMIRA therapy.

ADVERSE REACTIONS • The most common adverse reactions in HUMIRA clinical trials (incidence >10%) were: infections (e.g. upper respiratory, sinusitis), injection site reactions, headache, and rash.

Please see Brief Summary of full Prescribing Information on following pages.

Reference: 1. HUMIRA Injection [package insert]. North Chicago, IL: Abbott Laboratories.

©2012 Abbott Laboratories Abbott Park, IL 60064 64E-760907 January 2012 Printed in U.S.A.

Ad unit Project # must match this project # 64E-760907

HUMIRA® (adalimumab) WARNINGS: SERIOUS INFECTIONS AND MALIGNANCY SERIOUS INFECTIONS Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

HUMIRA should be discontinued if a patient develops a serious infection or sepsis.

Reported infections include: • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before HUMIRA use and during therapy. Treatment for latent TB should be initiated prior to HUMIRA use.

• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

• Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benets of treatment with HUMIRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. [See Warnings and Precautions and Adverse Reactions] MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member. [See Warnings and Precautions] Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases has occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males.

Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

INDICATIONS AND USAGE Rheumatoid Arthritis HUMIRA is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. HUMIRA can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

Juvenile Idiopathic Arthritis HUMIRA is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 4 years of age and older. HUMIRA can be used alone or in combination with methotrexate.

Psoriatic Arthritis HUMIRA is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. HUMIRA can be used alone or in combination with non-biologic DMARDs. Ankylosing Spondylitis HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Crohn’s Disease HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to iniximab.

Plaque Psoriasis HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Boxed Warnings and Warnings and Precautions].

CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS (see also Boxed WARNINGS) Serious Infections Patients treated with HUMIRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.

The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of HUMIRA and these biologic products is not recommended in the treatment of patients with RA [see Warnings and Precautions and Drug Interactions].

Treatment with HUMIRA should not be initiated in patients with an active infection, including localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be

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PROFESSIONAL BRIEF SUMMARY CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION at greater risk of infection. The risks and benets of treatment should be considered prior to initiating therapy in patients: • with chronic or recurrent infection; • who have been exposed to tuberculosis; • with a history of an opportunistic infection; • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or • with underlying conditions that may predispose them to infection.

Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving HUMIRA, including patients who have previously received treatment for latent or active tuberculosis. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating HUMIRA and periodically during therapy.

Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy.

Anti-tuberculosis therapy should also be considered prior to initiation of HUMIRA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be conrmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating antituberculosis therapy is appropriate for an individual patient.

Tuberculosis should be strongly considered in patients who develop a new infection during HUMIRA treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Monitoring Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with HUMIRA. HUMIRA should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with HUMIRA should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated.

Invasive Fungal Infections For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy.

Malignancies The risks and benets of TNF-blocker treatment including HUMIRA should be considered prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF blocker in patients who develop a malignancy.

Malignancies in Adults In the controlled portions of clinical trials of some TNF-blockers, including HUMIRA, more cases of malignancies have been observed among TNFblocker-treated adult patients compared to control-treated adult patients.

During the controlled portions of 32 global HUMIRA clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), and plaque psoriasis (Ps), malignancies, other than non-melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% condence interval) of 0.6 (0.38, 0.93) per 100 patientyears among 6694 HUMIRA-treated patients versus a rate of 0.5 (0.28, 1.05) per 100 patient-years among 3749 control-treated patients (median duration of treatment of 4 months for HUMIRA-treated patients and 4 months for control-treated patients). In 45 global controlled and uncontrolled clinical trials of HUMIRA in adult patients with RA, PsA, AS, CD and Ps, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in HUMIRA-treated patients in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).

In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., patients with COPD with a signicant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.

Non-Melanoma Skin Cancer During the controlled portions of 32 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, and Ps, the rate (95% condence interval) of NMSC was 0.7 (0.50, 1.11) per 100 patient-years among HUMIRA-treated patients and 0.2 (0.06, 0.56) per 100 patient-years among control-treated patients. All patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment should be examined for the presence of NMSC prior to and during treatment with HUMIRA. Lymphoma and Leukemia In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF blocker-treated patients compared to control-treated patients. In the controlled portions of 32 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, and Ps, 3 lymphomas occurred among 6694 HUMIRA-treated patients versus 1 among 3749 control-treated patients. In 45 global controlled and uncontrolled clinical trials of HUMIRA in adult patients with RA, PsA, AS, CD and Ps with a median duration of approximately 0.6 years, including 22,026 patients and over 32,000 patient-years of HUMIRA, the observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race). Rates of lymphoma in clinical trials of HUMIRA cannot be compared to rates of lymphoma in clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development

of lymphoma, even in the absence of TNF blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNFblocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.

Malignancies in Pediatric Patients and Young Adults Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HUMIRA is a member. Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months).

Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases has occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

Hypersensitivity Reactions In postmarketing experience, anaphylaxis and angioneurotic edema have been reported rarely following HUMIRA administration. If an anaphylactic or other serious allergic reaction occurs, administration of HUMIRA should be discontinued immediately and appropriate therapy instituted. In clinical trials of HUMIRA in adults, allergic reactions overall (e.g., allergic rash, anaphylactoid reaction, xed drug reaction, non-specied drug reaction, urticaria) have been observed in approximately 1% of patients.

Hepatitis B Virus Reactivation Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus.

In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating TNF blocker therapy. Prescribers should exercise caution in prescribing TNF blockers for patients identied as carriers of HBV. Adequate data are not available on the safety or efcacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. In patients who develop HBV reactivation, HUMIRA should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known.

Neurologic Reactions Use of TNF blocking agents, including HUMIRA, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Prescribers should exercise caution in considering the use of HUMIRA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

Hematological Reactions Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Adverse reactions of the hematologic system, including medically signicant cytopenia (e.g., thrombocytopenia, leukopenia) have been infrequently reported with HUMIRA. The causal relationship of these reports to HUMIRA remains unclear. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on HUMIRA. Discontinuation of HUMIRA therapy should be considered in patients with conrmed signicant hematologic abnormalities.

Use with Anakinra Concurrent use of anakinra (an interleukin-1 antagonist) and another TNFblocker, was associated with a greater proportion of serious infections and neutropenia and no added benet compared with the TNF-blocker alone in patients with RA. Therefore, the combination of HUMIRA and anakinra is not recommended [see Drug Interactions].

Heart Failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully.

Autoimmunity Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with HUMIRA, treatment should be discontinued [see Adverse Reactions].

Immunizations In a placebo-controlled clinical trial of patients with rheumatoid arthritis, no difference was detected in anti-pneumococcal antibody response between HUMIRA and placebo treatment groups when the pneumococcal polysaccharide vaccine and inuenza vaccine were administered concurrently with HUMIRA. Patients on HUMIRA may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving HUMIRA. It is recommended that juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HUMIRA therapy. Patients on HUMIRA may receive concurrent vaccinations, except for live vaccines.

Use with Abatacept In controlled trials, the concurrent administration of TNF-blockers and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benet in the treatment of RA. Therefore, the combination of abatacept with TNF-blockers including HUMIRA is not recommended [see Drug Interactions].

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ADVERSE REACTIONS Clinical Studies Experience The most serious adverse reactions were: • Serious Infections [see Warnings and Precautions] • Malignancies [see Warnings and Precautions] The most common adverse reaction with HUMIRA was injection site reactions.

In placebo-controlled trials, 20% of patients treated with HUMIRA developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.

The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of Studies RA-I, RA-II, RA-III and RA-IV was 7% for patients taking HUMIRA and 4% for placebo-treated patients. The most common adverse reactions leading to discontinuation of HUMIRA were clinical are reaction (0.7%), rash (0.3%) and pneumonia (0.3%).

Infections In the controlled portions of the 32 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD and Ps, the rate of serious infections was 4.7 per 100 patient-years in 6694 HUMIRA-treated patients versus a rate of 2.7 per 100 patient-years in 3749 control-treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions].

Tuberculosis and Opportunistic Infections In 45 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD and Ps that included 22,026 HUMIRA-treated patients, the rate of reported active tuberculosis was 0.22 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. In a subgroup of 8940 U.S. and Canadian HUMIRA-treated patients, the rate of reported active TB was 0.07 per 100 patient-years and the rate of positive PPD conversion was 0.06 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the rst eight months after initiation of therapy and may reect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.07 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal [see Warnings and Precautions].

Autoantibodies In the rheumatoid arthritis controlled trials, 12% of patients treated with HUMIRA and 7% of placebo-treated patients that had negative baseline ANA titers developed positive titers at week 24. Two patients out of 3046 treated with HUMIRA developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved following discontinuation of therapy. No patients developed lupus nephritis or central nervous system symptoms.

The impact of long-term treatment with HUMIRA on the development of autoimmune diseases is unknown.

Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of HUMIRA (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of HUMIRA-treated patients and 1.5% of control-treated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between HUMIRA and the liver enzyme elevations is not clear. In controlled Phase 3 trials of HUMIRA (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in patients with Crohn’s disease with control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of HUMIRA-treated patients and 0.9% of controltreated patients. In controlled Phase 3 trials of HUMIRA (initial dose of 80 mg then 40 mg every other week) in patients with plaque psoriasis with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of HUMIRA-treated patients and 1.8% of control-treated patients.

Immunogenicity Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab during the 6- to 12-month period. Approximately 5% (58 of 1062) of adult rheumatoid arthritis patients receiving HUMIRA developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate had a lower rate of antibody development than patients on HUMIRA monotherapy (1% versus 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibodypositive patients than among antibody-negative patients. The long-term immunogenicity of HUMIRA is unknown. In patients with juvenile idiopathic arthritis, adalimumab antibodies were identied in 16% of HUMIRA-treated patients. In patients receiving concomitant methotrexate, the incidence was 6% compared to 26% with HUMIRA monotherapy.

In patients with ankylosing spondylitis, the rate of development of antibodies to adalimumab in HUMIRA-treated patients was comparable to patients with rheumatoid arthritis. In patients with psoriatic arthritis, the rate of antibody development in patients receiving HUMIRA monotherapy was comparable to patients with rheumatoid arthritis; however, in patients receiving concomitant methotrexate the rate was 7% compared to 1% in rheumatoid arthritis. In patients with Crohn’s disease, the rate of antibody development was 3%. In patients with plaque psoriasis, the rate of antibody development with HUMIRA monotherapy was 8%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 ug/ml. Among the patients whose serum adalimumab levels were < 2 ug/ml (approximately 40% of total patients studied), the immunogenicity rate was 20.7%. In plaque psoriasis patients who were on HUMIRA monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal.

Other Adverse Reactions The data described below reect exposure to HUMIRA in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). HUMIRA was studied primarily in placebocontrolled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg HUMIRA every other week.

Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with HUMIRA 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion.

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Table 1. Adverse Reactions Reported by ≥5% of Patients Treated with HUMIRA During Placebo-Controlled Period of Rheumatoid Arthritis Studies HUMIRA 40 mg subcutaneous Placebo Every Other Week (N=705) (N=690) Adverse Reaction (Preferred Term) Respiratory Upper respiratory infection 17% 13% Sinusitis 11% 9% Flu syndrome 7% 6% Gastrointestinal Nausea 9% 8% Abdominal pain 7% 4% Laboratory Tests* Laboratory test abnormal 8% 7% Hypercholesterolemia 6% 4% Hyperlipidemia 7% 5% Hematuria 5% 4% Alkaline phosphatase increased 5% 3% Other Headache 12% 8% Rash 12% 6% Accidental injury 10% 8% Injection site reaction ** 8% 1% Back pain 6% 4% Urinary tract infection 8% 5% Hypertension 5% 3% * Laboratory test abnormalities were reported as adverse reactions in European trials ** Does not include injection site erythema, itching, hemorrhage, pain or swelling Juvenile Idiopathic Arthritis Clinical Studies In general, the adverse reactions in the HUMIRA-treated pediatric patients in the juvenile idiopathic arthritis (JIA) trial were similar in frequency and type to those seen in adult patients [see Warnings and Precautions, Adverse Reactions]. Important ndings and differences from adults are discussed in the following paragraphs.

HUMIRA was studied in 171 pediatric patients, 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, appendicitis. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster.

A total of 45% of children experienced an infection while receiving HUMIRA with or without concomitant MTX in the rst 16 weeks of treatment. The types of infections reported in HUMIRA-treated patients were generally similar to those commonly seen in JIA patients who are not treated with TNF blockers.

Upon initiation of treatment, the most common adverse reactions occurring in the pediatric population treated with HUMIRA were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in children receiving HUMIRA was granuloma annulare which did not lead to discontinuation of HUMIRA treatment.

In the rst 48 weeks of treatment, non-serious hypersensitivity reactions were seen in approximately 6% of children and included primarily localized allergic hypersensitivity reactions and allergic rash.

Isolated mild to moderate elevations of liver aminotransferases (ALT more common than AST) were observed in children with JIA exposed to HUMIRA alone; liver enzyme test elevations were more frequent among those treated with the combination of HUMIRA and MTX than those treated with HUMIRA alone. In general, these elevations did not lead to discontinuation of HUMIRA treatment.

In the JIA trial, 10% of patients treated with HUMIRA who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment.

No patient developed clinical signs of autoimmunity during the clinical trial.

Approximately 15% of children treated with HUMIRA developed mild-tomoderate elevations of creatine phosphokinase (CPK). Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK levels decreased or returned to normal in all patients. Most patients were able to continue HUMIRA without interruption.

Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies HUMIRA has been studied in 395 patients with psoriatic arthritis (PsA) in two placebo-controlled trials and in an open label study and in 393 patients with ankylosing spondylitis (AS) in two placebo-controlled studies. The safety prole for patients with PsA and AS treated with HUMIRA 40 mg every other week was similar to the safety prole seen in patients with RA, HUMIRA Studies RA-I through IV. Crohn’s Disease Clinical Studies HUMIRA has been studied in 1478 patients with Crohn’s disease in four placebo-controlled and two open-label extension studies. The safety prole for patients with Crohn’s disease treated with HUMIRA was similar to the safety prole seen in patients with RA. Plaque Psoriasis Clinical Studies HUMIRA has been studied in 1696 patients with plaque psoriasis in placebocontrolled and open-label extension studies. The safety prole for patients with plaque psoriasis treated with HUMIRA was similar to the safety prole seen in patients with RA with the following exceptions. In the placebo-controlled portions of the clinical trials in plaque psoriasis patients, HUMIRA-treated patients had a higher incidence of arthralgia when compared to controls (3% vs. 1%).

Postmarketing Experience Adverse reactions have been reported during post-approval use of HUMIRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to HUMIRA exposure.

Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis Respiratory disorders: Interstitial lung disease, including pulmonary brosis Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar) Vascular disorders: Systemic vasculitis

DRUG INTERACTIONS Methotrexate Although methotrexate (MTX) reduces the apparent adalimumab clearance, the data do not suggest the need for dose adjustment of either HUMIRA or MTX. Biologic Products In clinical studies in patients with RA, an increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no added benet; therefore, use of HUMIRA with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions]. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker.

There is insufcient information to provide recommendations regarding the concomitant use of HUMIRA and other biologic products for the treatment of RA, PsA, AS, Crohn’s Disease, and plaque psoriasis.

Live Vaccines Live vaccines should not be given concurrently with HUMIRA [see Warnings and Precautions].

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B - There are no adequate and well-controlled studies in pregnant women. Because animal reproduction and developmental studies are not always predictive of human response, HUMIRA should be used during pregnancy only if clearly needed.

Pregnancy Registry: To monitor outcomes of pregnant women exposed to HUMIRA, a pregnancy registry has been established. Physicians are encouraged to register patients by calling 1-877-311-8972.

Nursing Mothers It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from HUMIRA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use Safety and efcacy of HUMIRA in pediatric patients for uses other than juvenile idiopathic arthritis (JIA) have not been established.

Juvenile Idiopathic Arthritis In the JIA trial, HUMIRA was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age.

HUMIRA has not been studied in children less than 4 years of age, and there are limited data on HUMIRA treatment in children with weight <15 kg.

The safety of HUMIRA in pediatric patients in the JIA trial was generally similar to that observed in adults with certain exceptions [see Adverse Reactions].

Post-marketing cases of malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNFblockers including HUMIRA [see Warnings and Precautions].

Geriatric Use A total of 519 rheumatoid arthritis patients 65 years of age and older, including 107 patients 75 years of age and older, received HUMIRA in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these subjects and younger subjects. The frequency of serious infection and malignancy among HUMIRA treated subjects over 65 years of age was higher than for those under 65 years of age. Because there is a higher incidence of infections and malignancies in the elderly population in general, caution should be used when treating the elderly.

OVERDOSAGE Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies of HUMIRA have not been conducted to evaluate the carcinogenic potential or its effect on fertility. No clastogenic or mutagenic effects of HUMIRA were observed in the in vivo mouse micronucleus test or the Salmonella-Escherichia coli (Ames) assay, respectively.

PATIENT COUNSELING INFORMATION Patients or their caregivers should be provided the HUMIRA “Medication Guide” and provided an opportunity to read it and ask questions prior to initiation of therapy. The healthcare provider should ask the patient questions to determine any risk factors for treatment. Patients developing signs and symptoms of infection should seek medical evaluation immediately.

Patient Counseling Patients should be advised of the potential benets and risks of HUMIRA. Physicians should instruct their patients to read the Medication Guide before starting HUMIRA therapy and to reread each time the prescription is renewed.

• Infections Inform patients that HUMIRA may lower the ability of their immune system to ght infections. Instruct patients of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections.

• Malignancies Patients should be counseled about the risk of malignancies while receiving HUMIRA. • Allergic Reactions Patients should be advised to seek immediate medical attention if they experience any symptoms of severe allergic reactions. Advise latex-sensitive patients that the needle cap of the prelled syringe contains latex.

• Other Medical Conditions Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, neurological disease, autoimmune disorders, or cytopenias. Advise patients to report any symptoms suggestive of a cytopenia such as bruising, bleeding, or persistent fever.

Revised: December, 2011 Ref: 03-A569-R27 Abbott Laboratories North Chicago, IL 60064, U.S.A. Master # 64C-758202

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Imaging Insights:

Intestinal Tract Contrast Daniel Seckinger, MD Board Certified Interventional Radiologist You have seen your Gastro Health clinician, provided a history and had your physical exam. Your doctor can choose from many further investigative modalities be it laboratory, diagnostic testing, endoscopy or perhaps imaging. If the determination is made to obtain CT imaging, there’s a good chance it will be ordered with oral intestinal contrast, the white liquid a patient drinks prior to the CT exam of the abdomen and/or pelvis. “Darn it,“ you may think. In fact, you are not alone. Patient satisfaction surveys have shown that patients undergoing CT scan imaging find the drinking of liquid contrast to be the least desirable part of the whole exam – and that means even worse than the IV puncture for venous access.

“OK Doctor, I’ll have the CT Scan… But do I have to drink that nasty white stuff?”

What is contrast?

Contrast means a difference. It is derived from the Latin words contra “against” and stare “to stand”. Medical imaging contrast is something that makes a part of the inside of the body stand out against other body parts.

Contrast can be positive, neutral or negative. The white slightly chalky solution you may be asked to drink is an example of positive contrast. It contains a very small amount of the metallic element, barium. This inert element is not radioactive, it does not cause allergy, and it is not absorbed into the body. The barium sulfate gives contrast greater density than internal body parts. Its use is generally considered standard of care for initial CT imaging of the abdomen and pelvis. Neutral contrast is almost like water and is of similar density to internal body parts. It is used for detailed imaging of the intestinal wall for an exam called CT Enterography. Negative contrast, like air or gas, has much lower density than internal body parts and is used in a specialized exam called CT Colonography.

Why is contrast necessary?

Simply put, contrast helps the radiologist to detect disease. Just as important, it helps to determine when disease is not present. The presence of contrast indicates the intestinal structures to the radiologist.

For example, the pancreas is an organ in the deep central abdomen that often has adjacent intestinal loops which can mimic pancreas disease.

Contrast identifies the intestine and thus helps the radiologist to more accurately evaluate the pancreas. Peritoneal disease can be difficult to separate from intestinal loops without this solution. Contrast is particularly helpful in thin patients as they have little fat between internal abdominal structures. It assists imaging of the gastrointestinal tract in part by distention to provide more detailed images of the intestinal wall.

Abnormalities of the intestinal wall due to infection, decreased blood supply or tumor can be better detected with this solution. This is why it is important to drink all of the provided contrast, to achieve a sufficient volume in the gastrointestinal tract and thereby a satisfactory distention.

Do I absolutely have to drink intestinal contrast?

No, sometimes the patient does not need to drink the infamous liquid.

Studies of some abdominal organs as well as some follow up exams may not require contrast. A CT scan ordered for some types of abdominal pain may not need contrast either, particularly in the urgent evaluation of pain.

However, contrast is highly recommended for routine initial imaging and studies have supported the clinical utility of contrast over many years. The imaging center strives to obtain the highest quality medical images and perform a thorough exam for each patient. A complete exam with contrast done right the first time decreases the need for repeat imaging. Your Gastro Health clinician will determine whether imaging is indicated, and if so, which type of CT exam is most appropriate. Please understand that if your doctor has ordered the exam with oral contrast, it is because he or she wants the best possible diagnostic exam to further evaluate your clinical presentation. Contrast has been greatly improved and now has lemon, vanilla, berry or mocha flavoring. And remember, things could be worse; some centers advocate rectal contrast administration by way of catheter.

32 ::

GASTRO HEALTH MAGAZINE • 2012

Gastro Health

What You Might Not Know

About Antibiotics

Jose P. Ferrer, MD, FACP Board Certified Gastroenterologist Antibiotics are widely used in the prevention and treatment of infectious diseases. While antibiotics are safe for most people, it has been proven that a common side effect of the treatment is diarrhea. Symptoms can range from mild abdominal discomfort, watery diarrhea, to severe colitis and even death. Sure, the medicine kills the bad bacteria that make us sick, but it also destroys the good bacteria that keep our intestines in-line. Diarrhea is defined by the World Health Organization (WHO, 2008) as the passage of three or more loose or liquid stools per day, or more frequently than is normal for the individual.

According to several studies, diarrhea occurs between 5% and 39% of patients receiving antibiotics, depending on the population and the type of antibiotic. This undesired symptom may result directly from altered gastrointestinal motility (alterations in the contraction or movement of the intestines) or from disruption of the normal bacterial flora of the intestinal tract. However, the major cause of antibiotic-associated diarrhea is infection with Clostridium difficile bacteria.

Clostridium difficile, often called C. difficile, is a bacterium that represents a considerable public health hazard, known to cause symptoms that can even range to life-threatening inflammation of the colon. Illness from C. difficile typically occurs after use of antibiotic medications and has become more frequent, more severe and more difficult to treat. In the United States, it is responsible for more deaths than all other intestinal infections combined. It is suggested that up to 3 million cases of infection occur each year. If these statistics are accurate, it would make C. difficile infection the most common bacterial cause of diarrhea in the United States.

Aside from antibiotic use, the risk factors for C. difficile infection include advanced age, prior hospitalization, treatment with chemotherapy, living in a nursing home and use of proton pump inhibitor (medications used to suppress gastric acidity). Patients suffering from Inflammatory Bowel Disease, both ulcerative colitis and Crohn’s disease, are also particularly vulnerable to C. difficile infection and physicians recommend that their stools be tested whenever disease flares up with significant diarrhea.

Clostridium difficile is a bacteria that can exist in a spore or vegetative forms (a spore is a microorganism in a dormant or resting state). Outside the human colon, it survives in spore form which is resistant to heat, stomach acid and antibiotics. Patients with C. difficile infection shed spores in

stools, resulting in contamination of their skin, clothing, bedding and nearby environmental surfaces. Transmission is primarily via the fecal-oral route following transient contamination of the hands of the health care givers.

Once spores are in the colon, they convert to their fully functional and aggressive vegetative form, producing toxins that damage and inflame the lining of the colon resulting in colitis.

C. difficile infection recurs in up to 25% of the patients even after initial successful treatment, requiring another round of treatment with antibiotics.

Due to this high recurrence rate, immunologic approach to the prevention and treatment of recurrence are in development and include the use of immunoglobulins, anti-C. difficile toxin antibodies and active immunization with vaccines. The use of fecal transplant has also shown a high success rate in clinical trials.

Quoting Benjamin Franklin’s axiom that “an ounce of prevention is worth a pound of cure,” the following recommendations shall help in the prevention of antibiotic-associated diarrhea: • Do not demand/take antibiotics if your doctor says you don’t need them.

• Wash your hands thoroughly and frequently.

• Wear gloves when around a patient who has C. difficile infection.

The treatment of antibiotic-associated diarrhea consists of several steps: 1. Stopping the antibiotic causing the problem is an important initial step.

2. Administration of probiotics, which are live microorganisms (in most cases bacteria) that are similar to the beneficial microorganisms found in the human gastrointestinal tract. When administered in adequate amounts, they confer a health benefit on the host, in preventing and treating antibiotic-associated diarrhea.

3. If the patient has a stool specimen that tested positive for C. difficile, proper treatment with antibiotics should be started and the patient is advised not to use anti-diarrheal medications (Lomotil, Imodium, etc.) since their use could worsen the illness.

4. Finally, patients are advised to drink large amounts of fluids by mouth to prevent dehydration.

To lessen signs and symptoms of moderate to severe Crohn’s Disease in adults not helped enough by usual treatments Important Safety Information About CIMZIA® (certolizumab pegol) What is the most important information I should know about CIMZIA? CIMZIA is a prescription medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections. Your doctor should test you for TB before starting CIMZIA. Your doctor should monitor you closely for signs and symptoms of TB during your treatment with CIMZIA. Certain Types of Cancer There have been cases of unusual cancers in children and teenage patients using TNF-blocking agents. CIMZIA is not approved for use in pediatric patients. For people taking TNF-blocker medicines, including CIMZIA, the chances for getting lymphoma or other cancers may increase. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma.

Before starting CIMZIA, tell your doctor if you • Think you have an infection. You should not start taking CIMZIA if you have any kind of infection, are being treated for an infection or have signs of an infection such as fever, cough or flu-like symptoms or if you get a lot of infections or have infections that keep coming back.

• Have any open cuts or sores • Have diabetes or HIV • Have TB, or have been in close contact with someone with TB • Were born in, lived in, or traveled to countries where there is more risk of getting TB. Ask your doctor if you are not sure.

• Live or lived in certain parts of country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis). These infections may develop or become severe if you take CIMZIA. If you do not know if you have lived in these types of areas, ask your doctor.

• Have or have had hepatitis B • Have or have had any type of cancer • Have congestive heart failure • Have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis • Are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA • Are pregnant, planning to become pregnant, or breastfeeding. CIMZIA has not been studied in pregnant or nursing women.

• Especially tell your doctor if you take: Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab), Tysabri® (natalizumab), or another TNF blocker. You have a higher chance for serious infections when taking CIMZIA with these medicines. You should not take CIMZIA while you take one of these medicines.

After starting CIMZIA, if you get an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. CIMZIA can make you more likely to get infections or make any infection that you may have worse.

Patients 65 years of age or older, patients with other long term medical conditions, or taking certain other drugs that affect the immune system, such as corticosteroids or methotrexate, may be at a greater risk of infection.

What are the possible side effects of CIMZIA? CIMZIA can cause serious side effects including: Heart Failure including new heart failure or worsening of heart failure you already have; Nervous System Problems such as Multiple Sclerosis, seizures, or inflammation of the nerves of the eyes; Allergic Reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing; Hepatitis B virus reactivation in patients who carry the virus in their blood. In some cases, patients have died as a result of hepatitis B virus being reactivated.

Your doctor should monitor you carefully during treatment with CIMZIA if you carry the hepatitis B virus in your blood; Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding; Immune reactions including a lupus-like syndrome.

Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.

Call your doctor right away if you develop any of the above side effects or symptoms.

The most common side effects of CIMZIA are: upper respiratory infections (flu, cold), rash, and urinary tract infections (bladder infections).

Other side effects have happened in some people including new psoriasis or worsening of psoriasis you already have and injection site reactions.

You are encouraged to report negative side effects to FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

OXO, Good Grips and the associated logos are trademarks of Helen of Troy Limited and are used under license. © 2012 UCB, Inc. All rights reserved.

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Please see Brief Summary on following pages.

Pre-filled syringe designed for comfort and control in partnership with

I trust my gut.

™

Laura, Cimzia patient, school director, mom

Cimzia. Lasting Crohn’s symptom relief I trust.

CIMZIA was shown in clinical trials to reduce or help stop many moderate to severe Crohn’s symptoms, such as stomach pain and diarrhea, and to improve general well-being within a few short weeks in some patients. The majority of patients who responded and continued to take CIMZIA experienced sustained relief beyond 4 years with no increase in dose.

• CIMZIA is a steroid-free prescription treatment.

• CIMZIA can be injected at home or at your doctor’s office every 4 weeks after initial dosing. Your results may vary.

Ask your doctor about the benefits and risks of CIMZIA. Please read Important Safety Information on the adjacent page.

Visit cimzia.com/CD Call 1-877-55CIMZIA

Consumer Brief Summary for Cimzia® (certolizumab pegol)

CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION. Read the Medication Guide that comes with CIMZIA before you start using it, and before each injection of CIMZIA. This brief summary does not take the place of talking with your doctor about your medical condition or treatment.

What is the most important information I should know about CIMZIA? CIMZIA is a medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections have happened in patients taking CIMZIA. These infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some patients have died from these infections.

• Your doctor should test you for TB before starting CIMZIA. • Your doctor should monitor you closely for signs and symptoms of TB during treatment with CIMZIA. Before starting CIMZIA, tell your doctor if you: • think you have an infection. You should not start taking CIMZIA if you have any kind of infection.

• are being treated for an infection • have signs of an infection, such as a fever, cough, flu-like symptoms • have any open cuts or sores on your body • get a lot of infections or have infections that keep coming back • have diabetes • have HIV • have tuberculosis (TB), or have been in close contact with someone with TB • were born in, lived in, or traveled to countries where there is more risk for getting TB. Ask your doctor if you are not sure.

• live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may develop or become more severe if you take CIMZIA. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor.

• have or have had hepatitis B • use the medicine Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab), or Tysabri® (natalizumab) After starting CIMZIA, if you get an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. CIMZIA can make you more likely to get infections or make any infection that you may have worse. Patients 65 years of age or older, patients with other long term medical conditions, or taking certain other drugs that affect the immune system, such as corticosteroids or methotrexate, may be at a greater risk of infection.

Certain types of Cancer • There have been cases of unusual cancers in children and teenage patients using TNF-blocking agents.

• For people taking TNF-blocker medicines, including CIMZIA, the chances of getting lymphoma or other cancers may increase.

• People with RA, especially more serious RA, may have a higher chance of getting a kind of cancer called lymphoma.

See the section “What are the possible side effects of CIMZIA?” for more information.

What is CIMZIA? CIMZIA is a medicine called a Tumor Necrosis Factor (TNF) blocker. CIMZIA is used in adult patients to: • Lessen the signs and symptoms of moderately to severely active Crohn’s disease (CD) in adults who have not been helped enough by usual treatments.

• Treat moderately to severely active rheumatoid arthritis (RA).

It is not known whether CIMZIA is safe and effective in children.

What should I tell my doctor before starting treatment with CIMZIA? CIMZIA may not be right for you. Before starting CIMZIA, tell your doctor about all of your medical conditions, including if you: • have an infection. (See, “What is the most important information I should know about CIMZIA?”) • have or have had any type of cancer • have congestive heart failure • have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis • are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA. • are allergic to any of the ingredients in CIMZIA. See the end of this Brief Summary for a list of the ingredients in CIMZIA. Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. CIMZIA has not been studied in pregnant or nursing women.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Your doctor will tell you if it is okay to take your other medicines while taking CIMZIA. Especially, tell your doctor if you take: • Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab),Tysabri® (natalizumab).

You have a high chance for serious infections when taking CIMZIA with Kineret®,

Orencia®, Rituxan®, or Tysabri®.

• A TNF blocker: Remicade® (infliximab), Humira® (adalimumab), Enbrel® (etanercept), Simponi® (golimumab).

You should not take CIMZIA, while you take one of these medicines.

How should I use CIMZIA? CIMZIA is available as a lyophilized powder for reconstitution or a prefilled syringe. If your doctor prescribes the lyophilized pack, CIMZIA should be injected by a healthcare provider.

If your doctor prescribes the prefilled syringe, see the booklet called “Patient Instructions for Use” packaged in your CIMZIA prefilled syringe kit for complete instructions for use.

Do not give yourself an injection of CIMZIA unless you have been shown by your doctor or nurse, or they can train someone you know to help you with your injection. CIMZIA is given by an injection under the skin. Your doctor will tell you how much CIMZIA to inject and how often, based on your condition to be treated. Make sure to keep all of your injection and follow-up appointments with your doctor.

What are the possible side effects of CIMZIA? CIMZIA can cause serious side effects including: See “What is the most important information I should know about CIMZIA?” • Heart Failure including new heart failure or worsening of heart failure you already have. Symptoms include shortness of breath, swelling of your ankles or feet, or sudden weight gain.

• Nervous System Problems such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes. Symptoms include dizziness, numbness or tingling problems with your vision, and weakness in your arms or legs.

• Allergic Reactions. Signs of an allergic reaction include a skin rash, swelling of the face, tongue, lips, or throat, or trouble breathing.

• Hepatitis B virus reactivation in patients who carry the virus in their blood.

In some cases patients have died as a result of hepatitis B virus being reactivated.

Your doctor should monitor you carefully during treatment with CIMZIA if you carry the hepatitis B virus in your blood. Tell your doctor if you have any of the following symptoms: • feel unwell • tiredness (fatigue) • poor appetite • fever, skin rash, or joint pain • Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include a fever that doesn’t go away, bruising or bleeding very easily, or looking very pale.

• Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.

Call your doctor right away if you develop any of the above side effects or symptoms.

The most common side effects in people taking CIMZIA are: • upper respiratory infections (flu, cold) • rash • urinary tract infections (bladder infections) Other side effects with CIMZIA include: • Psoriasis. Some people using CIMZIA had new psoriasis or worsening of psoriasis they already had. Tell your doctor if you develop red scaly patches or raised bumps that are filled with pus. Your doctor may decide to stop your treatment with CIMZIA. • Injection site reactions. Redness, rash, swelling, itching or bruising can happen in some people. These symptoms will usually go away within a few days. If you have pain, redness, or swelling around the injection site that doesn’t go away within a few days or gets worse, call your doctor right away.

Tell your doctor about any side effect that bothers you or does not go away.

These are not all of the side effects with CIMZIA. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about CIMZIA Medicines are sometimes prescribed for purposes that are not mentioned in Medication Guides. Do not use CIMZIA for a condition for which it was not prescribed. Do not give CIMZIA to other people, even if they have the same condition. It may harm them.

This brief summary summarizes the most important information about CIMZIA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about CIMZIA that is written for health professionals.

For more information go to www.CIMZIA.com or call 1-866-4CIMZIA (424-6942).

Always keep CIMZIA, injection supplies, puncture-proof container, and all other medicines out of the reach of children.

What are the ingredients in CIMZIA? CIMZIA lyophilized powder: Active ingredient: certolizumab pegol. Inactive ingredients: sucrose, lactic acid, polysorbate. The pack contains Water for Injection, for reconstitution of the lyophilized powder. CIMZIA prefilled syringe: Active ingredient: certolizumab pegol. Inactive ingredients: sodium acetate, sodium chloride, and Water for Injection.

CIMZIA has no preservatives.

Product developed and manufactured for: UCB, Inc., 1950 Lake Park Drive, Smyrna, GA 30080

Cimzia® is a registered trademark of the UCB Group of companies. © 2011 UCB, Inc., Smyrna, GA 30080 All rights reserved.

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Please see back for complete eligibility rules.

Please see accompanying complete Prescribing Information.

Get up to 12 months of CIMZIA with no out-of-pocket costs.* Go to cimzia.com/CD To lessen signs and symptoms of moderate to severe Crohn’s disease in adults not helped enough by usual treatments.

Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria.

Please see Brief Summary on previous page. *Subject to eligibility. Restrictions may apply.

Word of the day: Pa•thol•o •gy

by Danna Prpich

noun; The study and diagnosis of disease. It is a branch of medicine in which specialized physicians work to obtain information from laboratory tests.

Patients with several different medical conditions, including all cases of cancer, have to be diagnosed by having a sample of tissue removed (this procedure is called a biopsy) and sent to a laboratory for examination. A team of licensed laboratory technologists processes the biopsy and a pathologist makes a diagnosis. The information is then delivered to the physicians caring directly for the patient.

In other words, pathologists and laboratory technologists work hand in hand with other doctors and health care professionals to help them improve a patient’s medical care by guiding their proper treatments. Pathologists are doctors who specialize at least four additional years after medical school to become familiar with all of the different types of diseases and relating symptoms that can affect the human body. As a result, the study of pathology and the integration of it in healthcare is one that plays a vital role in saving countless lives every year.

So why is being lectured about pathology important? Well without this diagnostic process, accurate decisions regarding analysis and treatments would be more of a challenge for doctors. In essence, this testing helps keep patients healthier for longer and gets faster results in deciding which treatment is best for

each condition. It helps people with diseases find out if the treatment they are undergoing is working. In fact, more than 70% of all decisions regarding accurate diagnosis, treatment and medical discharge rely on test results.

Pathology testing also plays an important part in screening and disease prevention programs which can range from testing a new born for conditions that could be treated early, to the detection of cancer. Pap smear screening, for instance, can increase the survival rate of cervical cancer patients by approximately 91% when detected at its earliest stage. But a doctor won’t know if the tissue found is cancerous until it is sent to a pathology laboratory.

Some common ways a biopsy can be sampled are by using a needle to withdraw tissue or fluid, surgery, or through an endoscopy. What is Endoscopy? It is a procedure that lets a doctor look inside your body in real time. An instrument called an endoscope is used, which is a long, thin tube with a tiny camera attached.

There are numerous resources online that can continue your understanding of pathology. You may come across interesting and informative articles, as well as glossaries to help you identify terms commonly used in pathology reports. Feel free to do some diagnosing of your own.

GASTRO HEALTH MAGAZINE • 2012

:: 37

Gastro Health

A New Era for the Treatment of

Hepatitis C

Hepatitis C virus (HCV) is a leading cause of liver-related mortality and the number one indication for liver transplantation in the United States.

Flavia Mendes, MD Board Certified Gastroenterologist

On May of 2011, the FDA approved two new drugs for the treatment of chronic hepatitis C: Incivek (Telaprevir, by Vertex)

Victrelis (Boceprevir, by Merck)

700mg (two 350 mg tablets)

800 mg (four 200 mg capsules)

Take three times daily with food

Take three times daily with food

These new treatments are also referred to as direct antiviral agents (DAA’s). The use of DAA’s in clinical practice comes nearly a decade after the implementation of pegylated interferon and ribavirin as the standard of care for the treatment of HCV, which was only able to cure less than half of the treated patients. The DAA’s have been anxiously waited for and they will significantly improve our ability to treat patients with hepatitis C.

Candidates for treatment with the new regimen include: • Adult patients (over the age of 18), infected with genotype 1 hepatitis C virus • Patients who have compensated liver disease, including cirrhotic stage disease • Patients who were never treated (treatment naive) or have previously failed interferon based therapy.

Both Victrelis (Boceprevir) and Incivek (Telaprevir) are designed to be used only in combination with pegylated interferon and ribavirin. They are not to be used by themselves due to the high rate of resistance development.

This scientific progress without a doubt opens a new era in the treatment of hepatitis C. The physicians and liver specialists at Gastro Health are all excited with the improved treatment efficacy and the possibility to help our patients who have been long waiting for a new hope in fighting against this disease.

Feeling the Burn?

by Danna Prpich

Chest burning, throat bunged; we know the feeling all too well. It’s the second symptom in Pepto Bismol’s catchy advertising slogan, “Nausea, heartburn, indigestion, upset stomach, diarrhea.”

For those lucky enough to not have experienced the nuisance and are not familiar with what it is, heartburn is a sensation of tightness, pain or irritation in the middle of the chest, sometimes radiating to the throat. It occurs when the lower esophageal sphincter (LES) – the passageway from your esophagus to your stomach – relaxes improperly causing food to come back up. Heartburn is the direct effect of acid reflux, which is when stomach acid regurgitates up into the esophagus.

It is also a major symptom of gastroesophageal reflux disease (GERD). Interestingly enough, heartburn has nothing to do with your heart and is instead caused by an excess of stomach acid refluxed into the esophagus.

One in ten Americans experience heartburn symptoms at least once a week, so you are not alone. Aside from certain foods, heartburn can have numerous different triggers, including certain medications and even stress. Although most people can manage this terrible discomfort on their own by making some lifestyle changes and getting their hands on some over-the-counter medications, the easiest way to prevent heartburn is by watching what we eat (along with when and how much, of course).

Here are some foods you might want to avoid, that may stimulate acid production and increase heartburn: Chocolate

Fried Foods

Carbonated Beverages

Acidic Foods

Unfortunately, it is high in fat and contains caffeine and other stimulants, such as theobromine.

The bubbles of carbonation expand inside the stomach causing increased pressure.

Caffeinated Beverages

One cup of coffee or espresso a day is fine.

Alcohol

Beer, liquor, and wine are believed to relax the valve at the bottom of the esophagus. Abstain if you can; otherwise, have only one cocktail or glass of wine a day, and completely avoid acidic mixers like orange juice or soda.

The single most recognized cause of reflux due to their high fat content.

This includes citrus foods such as oranges, grapefruits, and their juices, as well as tomatoes and tomato products.

High-Fat Meats

High-fat cuts of meat — beef, pork, lamb — stay longer in the stomach. Try cutting back to a lean cut of meat and eat it only once a week.

Spicy Foods

Not only do they irritate your taste buds, they also irritate the stomach.

Eating large meals increases pressure in the stomach and against the sphincter, so it is better to eat five or six small meals a day rather than three large ones. It is also important not to eat too quickly, giving your body time to digest. Putting the fork down between bites or counting your chews may help. Additionally, avoid lying down for two to three hours after you eat, and drink plenty of water.

Following these simple tips may help you avoid that dreadful burning sensation for good.

GASTRO HEALTH MAGAZINE • 2012

:: 39

Gastro Health

Dealing with Diverticulitis

Diverticulosis is the presence of pouches that form in the muscular wall of the colon that bulge outward.

Although these pouches generally produce no symptoms, when they become inflamed it is referred to as diverticulitis. You may also hear both conditions described as Diverticular Disease.

Richard E. Hernandez, MD Board Certified Gastroenterologist

Diverticulitis is initiated by the thinning of the wall of the diverticulum, or pouch, followed by a perforation that is then walled off by an inflammatory response. This inflammation results in pain, fever and general malaise. The presenting complaint is usually pain in the lower abdomen most often on the left side, and at times accompanied with a change in bowel habits.

The Cause The precise cause of diverticular thinning is not clear. One theory is that increased pressure in the lumen of the colon weakens the diverticular wall over time. Another is that stool can become trapped in the diverticulum leading to infection. Either way, reduced blood flow to the diverticulum probably plays a role in the process. One thing that does not produce diverticulitis is the ingestion of nuts, seeds and popcorn.

The advice to avoid these foods in the past was based on the incorrect notion that they helped produce diverticulitis by getting lodged in the diverticulum. This is no more than an old wives’ tale and as such should be ignored.

The Target Diverticulitis generally targets those over the age of 40. The illness shows no preference for a particular gender but does seem to be more common in men. It is also more common in “Westernized’ nations and relatively infrequent in Africa and Asia, which suggests that some environmental and lifestyle factors may play a role its development.

In fact, obesity, lack of exercise and inadequate dietary fiber ingestion have all been implicated as factors associated with diverticular disease.

People who smoke cigarettes are also more likely to be at risk.

The Treatment The diagnosis of diverticulitis is usually made on clinical grounds using easily obtained information from an interview and physical exam. The most useful test to confirm the diagnosis is a CT scan of the abdomen. In most cases if the physician has a high suspicion that the cause of a patient’s pain is diverticulitis, they will begin empiric therapy with antibiotics while awaiting the results of the CT scan. The illness

40 ::

GASTRO HEALTH MAGAZINE • 2012

becomes complicated in about 25% of cases. Some of these complications can include an abscess (a collection of pus), a fistula (an abnormal tract that connects the colon to another organ such as the urinary bladder), peritonitis (infection in the space in the abdomen outside the colon) and sepsis (an infection involving the whole body that can lead to failure of multiple organs). If complicated, diverticulitis will usually require surgery.

In addition to antibiotics, a diet of clear liquids is usually advised for the first couple of days of treatment until symptoms improve. Thereafter, the diet can be gently increased. Once the acute illness has resolved, a high-fiber diet should be started consisting of about 25 grams of fiber a day. Foods that contain fiber are those that originate in the ground such as fruits, vegetables and whole grains. Alternatively if it walks, runs, flies or swims it will contain no dietary fiber. It is also important not to confuse the symptoms of this illness with other syndromes that can cause similar lower abdominal pain, like appendicitis, colon cancer, ovarian cancer and ectopic pregnancy among others.

After the successful treatment of an initial episode of diverticulitis, a third of patients will remain asymptomatic, a third will have periodic episodes of lower abdominal Foods that contain fiber cramps and a third will go on are those that originate to have a second episode of in the ground such as diverticulitis. After this second fruits, vegetables episode, the rate of complications increases. In individuals who have and whole grains. recurrent bouts of diverticulitis, Alternatively if it walks, surgery is recommended and is runs, flies or swims it will curative in over 80% of cases. Once contain no dietary fiber. an episode has been treated and resolved, the entire colon should be evaluated with a colonoscopy six to eight weeks later. This interval is to allow the colon to heal completely before it is examined. The reason for the exam is to evaluate the extent of disease and to rule out the presence of abnormal lesions such as polyps or cancer.