Rheumatology Practice Management December 2014

DECEMBER 2014

www.RheumatologyPracticeManagement.com

VOLUME 2 • NUMBER 6

What Meaningful NORM Education Committee Develops Online Tools for Use Means to Members Your Practice

By Linda S. McKee, EFPM, Practice Administrator, Rheumatic Disease Associates, Willow Grove, PA

By Lynette Byrnes, Practice Administrator, Chairperson, NORM Education Committee; and Andrea Zlatkus, Practice Administrator, Co-chairperson, NORM Education Committee

W

e see the National Organiza­ ment questions as well as their ideas and tion of Rheumatology Man­ suggested best practices. From under­ agers (NORM) Listserv light standing latest PRACTITIONERS healthcare regula­ FOR OFFICE ADMINISTRATORS, RHEUMATOLOGISTS, PHYSICIAN ASSISTANTS, ANDthe NURSE up daily with members’ practice manage­ tions to training new staff members, we Continued on page 12

W

hat is Meaningful Use? If you ask someone at the US Department of Health & Human Services, he or she may tell you that Meaningful Use is an effort to maximize your electronic health record (EHR) technology to involve patients and caregivers in healthcare decisions or to improve care coordination as well Continued on page 18

Measuring Quality Improvement Healthcare in Rheumatology

By Helen Hinkle, Office Administrator, Rheumatology Associates of South Texas, San Antonio, TX

A

s administrators, we are forced to juggle more and more because of the Affordable Care Act and its plans to improve the cost of healthcare in the United States.

Measuring quality improvement is a great idea, but shouldn’t we have been doing this all along? These last 20 years in the medical field have taught me the good and the bad side of medicine, and Continued on page 17

In partnership with

Nat ion a l O r ga n iz at ion of o R he u m atolo g y Man a gers From the publishers of

© 2014 Engage Healthcare Communications, LLC

In This Issue

PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Director, Client Services Zach Ceretelle zceretelle@the-lynx-group.com Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne M. Cooper acooper@the-lynx-group.com Associate Editor Lara J. Lorton

DECEMBER 2014

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VOLUME 2 • NUMBER 6

Copyeditor Jessica Cheng Editorial Assistant Cara Guglielmon Production Manager Marie RS Borrelli The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca

Meaningful Use

What Meaningful Use Means to Your Practice.................................... 1

By Linda S. McKee, EFPM

Quality Metrics

Measuring Quality Improvement Healthcare in Rheumatology.... 1

By Helen Hinkle

FOR OFFICE ADMINISTRATORS, RHEUMATOLOGISTS, PHYSICIAN ASSISTANTS, AND NURSE PRACTITIONERS

NORM 2014 Highlights

NORM Education Committee Develops Online Tools for Members.................................................................................................. 1

By Lynette Byrnes and Andrea Zlatkus

OSHA Compliance: Tips Offered for Rheumatology Offices......... 14

By Rosemary Frei, MSc

Getting the Best from Your Medical Group........................................ 16

By Rosemary Frei, MSc

Continued on page 4

Director, Digital Media Anthony Romano Jr Digital Media Specialist Charles Easton IV Web Content Manager Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Managers Alyson Bruni Jini Gopalaswamy Project Manager Deanna Martinez Project Coordinator Mike Kodada IT Manager Kashif Javaid Administrative Services Team Leader Rachael Baranoski Office Coordinator Robert Sorensen Engage Healthcare Communications, LLC 1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-992-1880 fax: 732-992-1881

BPA Worldwide membership applied for January 2014.

MISSION STATEMENT Rheumatology healthcare requires providers to focus attention on financial concerns and strategic decisions that affect the bottom line. To continue to provide the high-quality care patients deserve, providers must master the ever-changing business of rheumatology. Rheumatology Practice Management offers process solutions for mem­ bers of the rheumatology care team—physicians, nurses, and auxiliary clinical staff, as well as executives, administrators, and coders/billers—to assist them in reimbursement, staffing, electronic health records, REMS, and compliance with state and federal regulations.

Rheumatology Practice Management™, ISSN 2164-4403 (print), is published 6 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512.

Copyright © 2014 by Engage Healthcare Communications, LLC. All rights reserved. Rheumatology Practice Management™ is a registered trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher. Printed in the United States of America.

The ideas and opinions expressed in Rheumatology Practice Management™ do not necessarily reflect those of the editorial board, the editors, or the publisher. Publication of an advertisement or other product mentioned in Rheumatology Practice Management ™ should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the editors nor the publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

POSTMASTER: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Rheumatology Practice Management™, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Fax: 732-992-1881. Yearly subscription rates: 1 year: $99.00 USD; 2 years: $149.00 USD; 3 years: $199.00 USD.

December 2014

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3

In This Issue

Continued from page 3

Human Resources

Tattletale or Whistleblower: What’s an Employer to Do?................................................................. 22

By Robert D. Orzechowski, MBA, SPHR

Rheumatoid Arthritis

Autoantibodies in Patients with RA Could Lead to More Precise Diagnosis, Therapy.................. 24

By E. K. Charles

Wealth Management

Ten Tips to Cut Your 2014 Taxes............................................................................................................ 25

By Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

Drug Update

Rasuvo (Methotrexate) Once-Weekly Subcutaneous Injection with Flexible Dosing Approved by the FDA for Rheumatoid Arthritis, Polyarticular Juvenile Idiopathic Arthritis, and Severe Psoriasis............................................................................................. 26

By Loretta Fala

EDITORIAL ADVISORY BOARD Editor-in-Chief Iris W. Nichols

President National Organization of Rheumatology Managers Wilmington, NC Practice Administrator Arthritis & Osteoporosis Consultants of the Carolinas Charlotte, NC

Ana Reyes-Cartagena

Director of Clinical Practice Arthritis & Rheumatism Associates, P.C. Wheaton, MD

Allyson D. Eakin, RN, OCN, CCM

Clinical Research Coordinator Arthritis & Osteoporosis Consultants of the Carolinas Charlotte, NC

Kyle C. Harner, MD

Helen Hinkle

Linda S. McKee, EFPM

Mark Post

Jay Salliotte

Practice Administrator Rheumatic Disease Associates Ltd Willow Grove, PA

I

Practice Administrator Premier HealthCare Associates, Inc Richmond, VA

Nancy Ellis

Practice Administrator Piedmont Arthritis Clinic Greenville, SC

4

Marjorie Collings

RHEUMATOLOGY PRACTICE MANAGEMENT

Carolina Arthritis Center Greenville, NC

Administrator North Texas Joint Care, P.A. Dallas, TX

I December 2014

Office Administrator Rheumatology Associates of South Texas San Antonio, TX

Business Manager Advanced Rheumatology Lansing, MI

DISCOVER A DIFFERENT STATE OF MIND WHEN YOU CAN’T PRESCRIBE MTX When MTX is no longer an option for your DMARD-IR RA patients, consider ACTEMRA The benefits and risks of treatment should be considered prior to initiating ACTEMRA. Patients should be monitored during treatment with ACTEMRA. Please see following brief summary of Prescribing Information, including Boxed WARNING, for additional important safety information.

MTX=methotrexate; DMARD-IR=disease-modifying antirheumatic drug inadequate responder.

Indication ACTEMRA is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

Important Safety Information

BOXED WARNING Serious Infections Serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving ACTEMRA. ACTEMRA should not be administered during an active infection, including localized infections. If a serious infection develops, ACTEMRA should be interrupted until the infection is controlled.

Prior to initiating ACTEMRA, a test for latent TB should be performed. If the test is positive, treatment for TB should be started prior to starting ACTEMRA. All patients should be monitored for active TB during treatment, even if initial latent TB test is negative.

The benefits and risks of treatment should be considered prior to initiating ACTEMRA in patients: • with chronic or recurrent infection • who have been exposed to TB • who have a history of serious or opportunistic infections • who have resided or traveled in areas of endemic TB or mycoses • with underlying conditions that may predispose them to infection Patients should be closely monitored for signs and symptoms of infection during and after treatment with ACTEMRA. Please see following pages for full Important Safety Information and brief summary of Prescribing Information.

®

WHEN MTX IS NO LONGER AN OPTION FOR YOUR DMARD-IR RA PATIENTS, CONSIDER ACTEMRA

Contact a rep at ActemraHCP.com for more information

ACTEMRA DELIVERED RAPID RESPONSE AT WEEK 2 AS A SINGLE AGENT AMBITION: ACR20 Responses Over Time (24 Weeks)1,2 100 ACTEMRA 8 mg/kg IV (every 4 weeks)* (n=286) MTX (n=284)

80

P<0.001

70

ACTEMRA MONOTHERAPY: RAPID RESPONSE AT WEEK 2

Patients (%)

60

53 40

20 Primary endpoint: ACR20 response at Week 24

0 BL

2

4

8

12 Time (weeks)

16

20

24

AMBITION: Pivotal, randomized, double-blind, Phase III clinical study in MTX-naïve/-free† patients with moderate to severe RA. The primary endpoint was ACR20 response at Week 24. Patients were treated with ACTEMRA 8 mg/ kg IV (every 4 weeks)* or an escalating dose of MTX. MTX dose was initiated at 7.5 mg/week and increased to a maximum dose of 20 mg/week within 8 weeks. The treatment period was 24 weeks. *The recommended starting dose for ACTEMRA IV is 4 mg/kg followed by an increase to 8 mg/ kg based on clinical response. † ACTEMRA is not indicated for the treatment of MTX-naïve patients with rheumatoid arthritis (RA).

ACTEMRA is indicated for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more DMARDs.

MTX=methotrexate.

Select Important Safety Information Contraindication ACTEMRA is contraindicated in patients with known hypersensitivity to ACTEMRA. Please see following pages for full Important Safety Information and brief summary of Prescribing Information.

ACTEMRA PROVIDED SIGNIFICANT ACR50 AND ACR70 RESPONSES VS MTX AT WEEK 24 *The recommended starting dose for ACTEMRA IV is 4 mg/kg followed by an increase to 8 mg/kg based on clinical response.

AMBITION: ACR Responses at Week 241,2 100

Patients (%)

80

ACTEMRA 8 mg/kg IV (every 4 weeks)* (n=286) MTX (n=284)

P=0.002

60 40

44 %

P<0.001

34 %

28 % 15 %

20

Select Important Safety Information Laboratory Monitoring Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications or interruptions may be required. Please see full Prescribing Information for more information.

0 ACR70

ACR50

ACTEMRA + MTX NOT SUPERIOR TO ACTEMRA ALONE ACT-RAY (Supportive Study): DAS28 <2.6 Responses at Week 243 100 ACTEMRA 8 mg/kg IV monotherapy (every 4 weeks)* (n=276) ACTEMRA 8 mg/kg IV (every 4 weeks)* + MTX (n=277)

Patients (%)

80

Primary endpoint not met Non-significant P=0.19

60

40

40 %

35 %

ACT-RAY: Supportive, Phase IIIb clinical trial in MTX-IR patients with moderate to severe RA. The study was designed to evaluate the superiority of combination ACTEMRA IV 8 mg/kg + MTX vs monotherapy ACTEMRA IV 8 mg/kg.* Patients received ACTEMRA IV + MTX or ACTEMRA IV every 4 weeks. The primary endpoint was the proportion of patients achieving DAS28 <2.6 at Week 24.

ACT-RAY primary endpoint was not met. *The recommended starting dose for ACTEMRA IV is 4 mg/kg followed by an increase to 8 mg/kg based on clinical response.

20

0 DAS28 <2.6 DAS=disease activity score.

速

Indication

ACTEMRA is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

Important Safety Information BOXED WARNING Serious Infections Serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving ACTEMRA. ACTEMRA should not be administered during an active infection, including localized infections. If a serious infection develops, ACTEMRA should be interrupted until the infection is controlled.

Prior to initiating ACTEMRA, a test for latent TB should be performed. If the test is positive, treatment for TB should be started prior to starting ACTEMRA. All patients should be monitored for active TB during treatment, even if initial latent TB test is negative.

The benefits and risks of treatment should be considered prior to initiating ACTEMRA in patients: • with chronic or recurrent infection • who have been exposed to TB • who have a history of serious or opportunistic infections • who have resided or traveled in areas of endemic TB or mycoses • with underlying conditions that may predispose them to infection Patients should be closely monitored for signs and symptoms of infection during and after treatment with ACTEMRA. CONTRAINDICATION ACTEMRA is contraindicated in patients with known hypersensitivity to ACTEMRA. WARNINGS AND PRECAUTIONS Gastrointestinal Perforations Use ACTEMRA with caution in patients who may be at increased risk for gastrointestinal (GI) perforation. Promptly evaluate patients presenting with new-onset abdominal symptoms for early identification of GI perforation.

Laboratory Monitoring Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications may be required. Please see full Prescribing Information for more information.

Immunosuppression The impact of treatment with ACTEMRA on the development of malignancies is not known, but malignancies were observed in clinical studies with ACTEMRA. ACTEMRA is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported in association with ACTEMRA and anaphylactic events with a fatal outcome have been reported with intravenous infusion of ACTEMRA. ACTEMRA for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis.

For ACTEMRA subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of ACTEMRA immediately and discontinue ACTEMRA permanently. Do not administer ACTEMRA to patients with known hypersensitivity to ACTEMRA. Anaphylaxis and other hypersensitivity reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of patients in the 6-month controlled trials of intravenous ACTEMRA, 0.2% (8 out of 4009) of patients in the intravenous all-exposure RA population, 0.7% (8 out of 1068) in the subcutaneous 6-month controlled RA trials, and in 0.7% (10 out of 1456) of patients in the subcutaneous all-exposure population.

Demyelinating Disorders Monitor patients for signs and symptoms of demyelinating disorders.

Prescribers should exercise caution in considering the use of ACTEMRA in patients with preexisting or recent-onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment Treatment with ACTEMRA is not recommended in patients with active hepatic disease or hepatic impairment.

Vaccinations Avoid use of live vaccines concurrently with ACTEMRA. Patients should be brought up to date on all recommended vaccinations prior to initiation of ACTEMRA therapy.

ADVERSE REACTIONS The most common serious adverse reactions were serious infections. In the ACTEMRA-IV monotherapy clinical study, the rate of serious infections was 3.6 per 100 patient-years in the ACTEMRA group and 1.5 per 100 patient-years in the methotrexate group. The rate of serious infections in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD groups was 4.4 and 5.3 events per 100 patient-years, respectively, compared to 3.9 events per 100 patient-years in the placebo plus DMARD group.

In the 5 Phase III clinical trials, the most common adverse reactions (≥5% of patients treated with ACTEMRA-IV) through 6 months were: ACTEMRA-IV ACTEMRA-IV ACTEMRA-IV 8 mg/kg 4 mg/kg 8 mg/kg Placebo Monotherapy Methotrexate + DMARDs + DMARDs + DMARDs (%) (%) (%) (%) (%) URTI

7

5

6

8

6

Nasopharyngitis

7

6

4

6

4

Headache

7

2

6

5

3

Hypertension

6

2

4

4

3

Increased ALT

6

4

3

3

1

The safety observed for ACTEMRA administered subcutaneously was consistent with the known safety profile of intravenous ACTEMRA, with the exception of injection-site reactions, which were more common with ACTEMRA-SC compared with placebo-SC injections (IV-arm).

In the 6-month control period, in SC-I, the frequency of injection-site reactions was 10.1% (64/631) and 2.4% (15/631) for the weekly ACTEMRA-SC and placebo-SC (IV-arm) group, respectively. In SC-II, the frequency of injection-site reactions was 7.1% (31/437) and 4.1% (9/218) for the every other week ACTEMRA-SC and placebo-SC groups, respectively. These injection-site reactions were mild to moderate in severity. The majority resolved without any treatment and none necessitated drug discontinuation.

USE IN PREGNANCY: PREGNANCY CATEGORY C Adequate and well-controlled studies with ACTEMRA have not been conducted in pregnant women. ACTEMRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.

PATIENT COUNSELING INFORMATION Advise patients of the potential benefits and risks of ACTEMRA. Physicians should instruct their patients to read the Medication Guide before starting ACTEMRA therapy. Inform patients that ACTEMRA may lower their resistance to infections and instruct patients of the importance of contacting their doctor immediately when symptoms of an infection appear. Inform patients that some patients receiving ACTEMRA have had serious side effects in the stomach and intestines and instruct patients of the importance of contacting their doctor immediately when symptoms of severe, persistent abdominal pain appear. Assess patient suitability for home use for SC injection. Inform patients that some patients have had serious allergic reactions including anaphylaxis and advise them to seek immediate medical attention if symptoms occur.

Please see following brief summary of Prescribing Information, including Boxed WARNING, for additional important safety information.

References 1. Jones G, et al. Ann Rheum Dis. 2010;69:88-96. 2. Data on file. AMBITION Clinical Study Report. Genentech Inc. 3. Dougados M, et al. Presented at EULAR Annual European Congress of Rheumatology; June 6-9, 2012; Berlin, Germany. Poster THU0093.

© 2014 Genentech USA, Inc. All rights reserved. ACT/102714/0027

®

ACTEMRA® (tocilizumab) Injection, for intravenous use Injection, for subcutaneous use This is a brief summary. Before prescribing, please refer to the full Prescribing Information.

WARNING: RISK OF SERIOUS INFECTIONS

Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions, Adverse Reactions]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt ACTEMRA until the infection is controlled.

Reported infections include: • Active tuberculosis, which may present with pulmonary or extrapulmonary disease.

Patients should be tested for latent tuberculosis before ACTEMRA use and during therapy. Treatment for latent infection should be initiated prior to ACTEMRA use.

• Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis.

Patients with invasive fungal infections may present with disseminated, rather than localized, disease.

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

The risks and benefits of treatment with ACTEMRA 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 ACTEMRA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions].

INDICATIONS AND USAGE ACTEMRA® (tocilizumab) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

ACTEMRA is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

ACTEMRA is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

DOSAGE AND ADMINISTRATION ACTEMRA may be used alone or in combination with methotrexate: and in RA, other nonbiologic DMARDs may be used.

Recommended Intravenous (IV) Adult RA Dosage When used in combination with DMARDs or as monotherapy the recommended starting Patients who have had an inadequate dose is 4 mg per kg followed by an increase response to one or more DMARD to 8 mg per kg based on clinical response • Reduction of dose from 8 mg per kg to 4 mg per kg is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia [see Warnings and Precautions and Adverse Reactions].

• Doses exceeding 800 mg per infusion are not recommended in RA patients [see Clinical Pharmacology].

Recommended Subcutaneous (SC) Adult RA Dosage 162 mg administered subcutaneously every other week, followed by an increase to every Patients less than 100 kg weight week based on clinical response 162 mg administered subcutaneously every Patients at or above 100 kg weight week When transitioning from ACTEMRA intravenous therapy to subcutaneous administration administer the first subcutaneous dose instead of the next scheduled intravenous dose.

Interruption of dose or reduction in frequency of administration of subcutaneous dose from every week to every other week dosing is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia (see Dosage and Administration, Warnings and Precautions, and Adverse Reactions).

CONTRAINDICATIONS ACTEMRA is contraindicated in patients with known hypersensitivity to ACTEMRA [see Warnings and Precautions].

WARNINGS AND PRECAUTIONS

Serious Infections Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, protozoal, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including ACTEMRA for rheumatoid arthritis. The most common serious infections included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis [see Adverse Reactions].

Among opportunistic infections, tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis were reported with ACTEMRA. Other serious infections, not reported in clinical studies, may also occur (e.g., histoplasmosis, coccidioidomycosis, listeriosis).

Patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids which in addition to rheumatoid arthritis may predispose them to infections.

Do not administer ACTEMRA in patients with an active infection, including localized infections.

The risks and benefits of treatment should be considered prior to initiating ACTEMRA in patients: • with chronic or recurrent infection • who have been exposed to tuberculosis • with a history of serious or an opportunistic infection

• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses • with underlying conditions that may predispose them to infection

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ACTEMRA, as signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants [see Dosage and Administration, Adverse Reactions and Patient Counseling Information].

Hold ACTEMRA if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with ACTEMRA should undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.

Tuberculosis Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating ACTEMRA. Consider anti-tuberculosis therapy prior to initiation of ACTEMRA 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.

Cosmos Communications

Closely monitor patients for the development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy.

It is recommended that patients be screened for latent tuberculosis infection prior to starting ACTEMRA. The incidence of tuberculosis in worldwide clinical development programs is 0.1%. Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before initiating ACTEMRA. Viral Reactivation Viral reactivation has been reported with immunosuppressive biologic therapies and cases of herpes zoster exacerbation were observed in clinical studies with ACTEMRA. No cases of Hepatitis B reactivation were observed in the trials; however patients who screened positive for hepatitis were excluded.

Gastrointestinal Perforations

Events of gastrointestinal perforation have been reported in clinical trials, primarily as complications of diverticulitis in RA patients. ACTEMRA should be used with caution in patients who may be at increased risk for gastrointestinal perforation. Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of gastrointestinal perforation [see Adverse Reactions].

Laboratory Parameters

Rheumatoid Arthritis Neutropenia Treatment with ACTEMRA was associated with a higher incidence of neutropenia.

Infections have been uncommonly reported in association with treatment-related neutropenia in long-term extension studies and postmarketing clinical experience.

– It is not recommended to initiate ACTEMRA treatment in patients with a low neutrophil count i.e., absolute neutrophil count (ANC) less than 2000/mm3. In patients who develop an absolute neutrophil count less than 500/mm3 treatment is not recommended.

– Monitor neutrophils 4 to 8 weeks after start of therapy and every 3 months thereafter.

For recommended modifications based on ANC results, please consult the full Prescribing Information.

Thrombocytopenia Treatment with ACTEMRA was associated with a reduction in platelet counts. Treatment-related reduction in platelets was not associated with serious bleeding events in clinical trials [see Adverse Reactions].

– It is not recommended to initiate ACTEMRA treatment in patients with a platelet count below 100,000/mm3. In patients who develop a platelet count less than 50,000/mm3 treatment is not recommended.

– Monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter. For recommended modifications based on platelet counts, please consult the full Prescribing Information.

Elevated Liver Enzymes Treatment with ACTEMRA was associated with a higher incidence of transaminase elevations. These elevations did not result in apparent permanent or clinically evident hepatic injury in clinical trials [see Adverse Reactions]. Increased frequency and magnitude of these elevations was observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with ACTEMRA. In one case, a patient who had received ACTEMRA 8 mg/kg monotherapy without elevations in transaminases experienced elevation in AST to above 10x ULN and elevation in ALT to above 16x ULN when MTX was initiated in combination with ACTEMRA. Transaminases normalized when both treatments were held, but elevations recurred when MTX and ACTEMRA were restarted at lower doses. Elevations resolved when MTX and ACTEMRA were discontinued.

– It is not recommended to initiate ACTEMRA treatment in patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN treatment is not recommended.

– Monitor ALT and AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter.

When clinically indicated, other liver function tests such as bilirubin should be considered.

For recommended modifications based on transaminases, please consult the full Prescribing Information.

Lipid Abnormalities Treatment with ACTEMRA was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterol, and/or HDL cholesterol [see Adverse Reactions].

– Assess lipid parameters approximately 4 to 8 weeks following initiation of ACTEMRA therapy, then at approximately 24 week intervals.

– Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia.

Immunosuppression The impact of treatment with ACTEMRA on the development of malignancies is not known but malignancies were observed in clinical studies [see Adverse Reactions].

ACTEMRA is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis and death, have been reported in association with ACTEMRA [see Adverse Reactions] and anaphylactic events with a fatal outcome have been reported with intravenous infusion of ACTEMRA. Anaphylaxis and other hypersensitivity reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of patients in the 6-month controlled trials of intravenous ACTEMRA, 0.2% (8 out of 4009) of patients in the intravenous all-exposure RA population, 0.7% (8 out of 1068) in the subcutaneous 6-month controlled RA trials, and in 0.7% (10 out of 1465) of patients in the subcutaneous all-exposure population. Injection site reactions were categorized separately [see Adverse Reactions].

In the postmarketing setting, events of hypersensitivity reactions, including anaphylaxis and death, have occurred in patients treated with a range of doses of intravenous ACTEMRA, with or without concomitant arthritis therapies. Events have occurred in patients who received premedication. Hypersensitivity, including anaphylaxis events, have occurred both with and without previous hypersensitivity reactions and as early as the first infusion of ACTEMRA [see Adverse Reactions]. ACTEMRA for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis.

For ACTEMRA subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, administration of ACTEMRA should be stopped immediately and ACTEMRA should be permanently discontinued. Do not administer ACTEMRA to patients with known hypersensitivity to ACTEMRA [see Contraindications and Adverse Reactions].

Demyelinating Disorders The impact of treatment with ACTEMRA on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA clinical studies. Patients should be closely monitored for signs and symptoms potentially indicative of demyelinating disorders. Prescribers should exercise caution in considering the use of ACTEMRA in patients with preexisting or recent onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment Treatment with ACTEMRA is not recommended in patients with active hepatic disease or hepatic impairment [see Adverse Reactions, Use in Specific Populations].

Vaccinations Avoid use of live vaccines concurrently with ACTEMRA as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving ACTEMRA.

1

Q1

Q2

No data are available on the effectiveness of vaccination in patients receiving ACTEMRA. Because IL-6 inhibition may interfere with the normal immune response to new antigens, it is recommended that all patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating ACTEMRA therapy.

The interval between live vaccinations and initiation of ACTEMRA therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.

ADVERSE REACTIONS Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

Clinical Trials Experience in Rheumatoid Arthritis Patients Treated with Intravenous ACTEMRA (ACTEMRA-IV) The ACTEMRA-IV data in rheumatoid arthritis (RA) includes 5 double-blind, controlled, multicenter studies. In these studies, patients received doses of ACTEMRA-IV 8 mg per kg monotherapy (288 patients), ACTEMRA-IV 8 mg per kg in combination with DMARDs (including methotrexate) (1582 patients), or ACTEMRA-IV 4 mg per kg in combination with methotrexate (774 patients).

The all exposure population includes all patients in registration studies who received at least one dose of ACTEMRA-IV. Of the 4009 patients in this population, 3577 received treatment for at least 6 months, 3309 for at least one year; 2954 received treatment for at least 2 years and 2189 for 3 years. All patients in these studies had moderately to severely active rheumatoid arthritis. The study population had a mean age of 52 years, 82% were female and 74% were Caucasian. The most common serious adverse reactions were serious infections [see Warnings and Precautions]. The most commonly reported adverse reactions in controlled studies up to 24 weeks (occurring in at least 5% of patients treated with ACTEMRA-IV monotherapy or in combination with DMARDs) were upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased ALT. The proportion of patients who discontinued treatment due to any adverse reactions during the double-blind, placebo-controlled studies was 5% for patients taking ACTEMRA-IV and 3% for placebo-treated patients. The most common adverse reactions that required discontinuation of ACTEMRA-IV were increased hepatic transaminase values (per protocol requirement) and serious infections.

Overall Infections In the 24 week, controlled clinical studies, the rate of infections in the ACTEMRA-IV monotherapy group was 119 events per 100 patient-years and was similar in the methotrexate monotherapy group. The rate of infections in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD group was 133 and 127 events per 100 patient-years, respectively, compared to 112 events per 100 patient-years in the placebo plus DMARD group. The most commonly reported infections (5% to 8% of patients) were upper respiratory tract infections and nasopharyngitis.

The overall rate of infections with ACTEMRA-IV in the all exposure population remained consistent with rates in the controlled periods of the studies.

Serious Infections In the 24 week, controlled clinical studies, the rate of serious infections in the ACTEMRA-IV monotherapy group was 3.6 per 100 patient-years compared to 1.5 per 100 patient-years in the methotrexate group. The rate of serious infections in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD group was 4.4 and 5.3 events per 100 patient-years, respectively, compared to 3.9 events per 100 patient-years in the placebo plus DMARD group.

In the all-exposure population, the overall rate of serious infections remained consistent with rates in the controlled periods of the studies. The most common serious infections included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Cases of opportunistic infections have been reported [see Warnings and Precautions].

Gastrointestinal Perforations During the 24 week, controlled clinical trials, the overall rate of gastrointestinal perforation was 0.26 events per 100 patient-years with ACTEMRA-IV therapy.

In the all-exposure population, the overall rate of gastrointestinal perforation remained consistent with rates in the controlled periods of the studies. Reports of gastrointestinal perforation were primarily reported as complications of diverticulitis including generalized purulent peritonitis, lower GI perforation, fistula and abscess. Most patients who developed gastrointestinal perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroids, or methotrexate [see Warnings and Precautions].

The relative contribution of these concomitant medications versus ACTEMRA-IV to the development of GI perforations is not known.

Infusion Reactions In the 24 week, controlled clinical studies, adverse events associated with the infusion (occurring during or within 24 hours of the start of infusion) were reported in 8% and 7% of patients in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD group, respectively, compared to 5% of patients in the placebo plus DMARD group. The most frequently reported event on the 4 mg per kg and 8 mg per kg dose during the infusion was hypertension (1% for both doses), while the most frequently reported event occurring within 24 hours of finishing an infusion were headache (1% for both doses) and skin reactions (1% for both doses), including rash, pruritus and urticaria. These events were not treatment limiting.

Anaphylaxis Hypersensitivity reactions requiring treatment discontinuation, including anaphylaxis, associated with ACTEMRA-IV were reported in 0.1% (3 out of 2644) in the 24 week, controlled trials and in 0.2% (8 out of 4009) in the all-exposure population. These reactions were generally observed during the second to fourth infusion of ACTEMRA-IV. Appropriate medical treatment should be available for immediate use in the event of a serious hypersensitivity reaction [see Warnings and Precautions].

Laboratory Abnormalities Neutropenia In the 24 week, controlled clinical studies, decreases in neutrophil counts below 1000 per mm3 occurred in 1.8% and 3.4% of patients in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD group, respectively, compared to 0.1% of patients in the placebo plus DMARD group. Approximately half of the instances of ANC below 1000 per mm3 occurred within 8 weeks of starting therapy. Decreases in neutrophil counts below 500 per mm3 occurred in 0.4% and 0.3% of patients in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD, respectively, compared to 0.1% of patients in the placebo plus DMARD group.

There was no clear relationship between decreases in neutrophils below 1000 per mm3 and the occurrence of serious infections. In the all-exposure population, the pattern and incidence of decreases in neutrophil counts remained consistent with what was seen in the 24 week controlled clinical studies [see Warnings and Precautions].

Thrombocytopenia In the 24 week, controlled clinical studies, decreases in platelet counts below 100,000 per mm3 occurred in 1.3% and 1.7% of patients on 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD, respectively, compared to 0.5% of patients on placebo plus DMARD, without associated bleeding events.

In the all-exposure population, the pattern and incidence of decreases in platelet counts remained consistent with what was seen in the 24 week controlled clinical studies [see Warnings and Precautions].

Elevated Liver Enzymes Liver enzyme abnormalities are summarized in Table 1. In patients experiencing liver enzyme elevation, modification of treatment regimen, such as reduction in the dose of concomitant DMARD, interruption of ACTEMRA-IV, or reduction in ACTEMRA-IV dose, resulted in decrease or normalization of liver enzymes [see Dosage and Administration]. These elevations were not associated with clinically relevant increases in direct bilirubin, nor were they associated with clinical evidence of hepatitis or hepatic insufficiency [see Warnings and Precautions].

Table 1 Incidence of Liver Enzyme Abnormalities in the 24 Week Controlled Period of Studies I to V* ACTEMRA 8 mg per kg MONO THERAPY

Metho trexate

ACTEMRA 4 mg per kg + DMARDs

ACTEMRA 8 mg per kg + DMARDs

Placebo +

N = 288 (%)

N = 284 (%)

N = 774 (%)

N = 1582 (%)

N = 1170 (%)

AST (U/L) > ULN to 3x ULN 22 26 34 41 17 > 3x ULN to 5x 0.3 2 1 2 0.3 ULN > 5x ULN 0.7 0.4 0.1 0.2 <0.1 ALT (U/L) > ULN to 3x 36 33 45 48 23 ULN > 3x ULN to 5x 1 4 5 5 1 ULN > 5x ULN 0.7 1 1.3 1.5 0.3 ULN = Upper Limit of Normal. *For a description of these studies, see Section 14, Clinical Studies in the full Prescribing Information.

In the all-exposure population, the elevations in ALT and AST remained consistent with what was seen in the 24 week, controlled clinical trials Lipids Elevations in lipid parameters (total cholesterol, LDL, HDL, triglycerides) were first assessed at 6 weeks following initiation of ACTEMRA-IV in the controlled 24 week clinical trials. Increases were observed at this time point and remained stable thereafter. Increases in triglycerides to levels above 500 mg per dL were rarely observed. Changes in other lipid parameters from baseline to week 24 were evaluated and are summarized below: – Mean LDL increased by 13 mg per dL in the ACTEMRA 4 mg per kg+DMARD arm, 20 mg per dL in the ACTEMRA 8 mg per kg+DMARD, and 25 mg per dL in ACTEMRA 8 mg per kg monotherapy.

– Mean HDL increased by 3 mg per dL in the ACTEMRA 4 mg per kg+DMARD arm, 5 mg per dL in the ACTEMRA 8 mg per kg+DMARD, and 4 mg per dL in ACTEMRA 8 mg per kg monotherapy.

– Mean LDL/HDL ratio increased by an average of 0.14 in the ACTEMRA 4 mg per kg+DMARD arm, 0.15 in the ACTEMRA 8 mg per kg+DMARD, and 0.26 in ACTEMRA 8 mg per kg monotherapy.

– ApoB/ApoA1 ratios were essentially unchanged in ACTEMRA-treated patients.

Elevated lipids responded to lipid lowering agents.

In the all-exposure population, the elevations in lipid parameters remained consistent with what was seen in the 24 week, controlled clinical trials.

Immunogenicity In the 24 week, controlled clinical studies, a total of 2876 patients have been tested for anti-tocilizumab antibodies. Forty-six patients (2%) developed positive antitocilizumab antibodies, of whom 5 had an associated, medically significant, hypersensitivity reaction leading to withdrawal. Thirty patients (1%) developed neutralizing antibodies.

The data reflect the percentage of patients whose test results were positive for antibodies to tocilizumab in specific assays. The observed incidence of antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to tocilizumab with the incidence of antibodies to other products may be misleading.

Malignancies During the 24 week, controlled period of the studies, 15 malignancies were diagnosed in patients receiving ACTEMRA-IV, compared to 8 malignancies in patients in the control groups. Exposure-adjusted incidence was similar in the ACTEMRA-IV groups (1.32 events per 100 patient-years) and in the placebo plus DMARD group (1.37 events per 100 patient-years).

In the all-exposure population, the rate of malignancies remained consistent with the rate observed in the 24 week, controlled period [see Warnings and Precautions].

Other Adverse Reactions Adverse reactions occurring in 2% or more of patients on 4 or 8 mg per kg ACTEMRA-IV plus DMARD and at least 1% greater than that observed in patients on placebo plus DMARD are summarized in Table 2.

Table 2 Adverse Reactions Occurring in at Least 2% or More of Patients on 4 or 8 mg per kg ACTEMRA-IV plus DMARD and at Least 1% Greater Than That Observed in Patients on Placebo plus DMARD ACTEMRA 8 mg per kg Mono therapy

Metho trexate

ACTEMRA 4 mg per kg + DMARDs

ACTEMRA 8 mg per kg + DMARDs

Placebo +

N = 1582 N = 1170 N = 774 N = 284 N = 288 Preferred Term (%) (%) (%) (%) (%) Upper Respiratory 7 5 6 8 6 Tract Infection Nasopharyngitis 7 6 4 6 4 Headache 7 2 6 5 3 Hypertension 6 2 4 4 3 ALT increased 6 4 3 3 1 Dizziness 3 1 2 3 2 Bronchitis 3 2 4 3 3 Rash 2 1 4 3 1 Mouth Ulceration 2 2 1 3 1 Abdominal Pain 2 2 3 3 2 Upper Gastritis 1 2 1 2 1 Transaminase 1 5 2 2 1 increased Other infrequent and medically relevant adverse reactions occurring at an incidence less than 2% in rheumatoid arthritis patients treated with ACTEMRA-IV in controlled trials were: Infections and Infestations: oral herpes simplex Gastrointestinal disorders: stomatitis, gastric ulcer Investigations: weight increased, total bilirubin increased Blood and lymphatic system disorders: leukopenia General disorders and administration site conditions: edema peripheral Respiratory, thoracic, and mediastinal disorders: dyspnea, cough Eye disorders: conjunctivitis Renal disorders: nephrolithiasis Endocrine disorders: hypothyroidism

Clinical Trials Experience in Rheumatoid Arthritis Patients Treated with Subcutaneous ACTEMRA (ACTEMRA-SC) The ACTEMRA-SC data in rheumatoid arthritis (RA) includes 2 double-blind, controlled, multicenter studies. Study SC-I was a non-inferiority study that compared the efficacy and safety of tocilizumab 162 mg administered every week subcutaneously (SC) and 8 mg/kg intravenously (IV) every four weeks in 1262 adult subjects with rheumatoid arthritis. Study SC-II was a placebo controlled superiority study that evaluated the safety and efficacy of tocilizumab 162 mg administered every other week SC or placebo in 656 patients. All patients in both studies received background non-biologic DMARDs. The safety observed for ACTEMRA administered subcutaneously was consistent with the known safety profile of intravenous ACTEMRA, with the exception of injection site reactions, which were more common with ACTEMRA-SC compared with placebo SC injections (IV arm).

Injection Site Reactions In the 6-month control period, in SC-I, the frequency of injection site reactions was 10.1% (64/631) and 2.4% (15/631) for the weekly ACTEMRA-SC and placebo SC (IV-arm) groups, respectively. In SC-II, the frequency of injection site reactions was 7.1% (31/437) and 4.1% (9/218) for the every other week SC ACTEMRA and placebo groups, respectively. These injection site reactions (including erythema, pruritus, pain and hematoma) were mild to moderate in severity. The majority resolved without any treatment and none necessitated drug discontinuation.

Immunogenicity In the 6-month control period in SC-I, 0.8% (5/625) in the ACTEMRA-SC arm and 0.8% (5/627) in the IV arm developed anti-tocilizumab antibodies; of these, all developed neutralizing antibodies. In SC-II, 1.6% (7/434) in the ACTEMRA-SC arm compared with 1.4 % (3/217) in the placebo arm developed anti- tocilizumab antibodies; of these, 1.4% (6/434) in the ACTEMRA-SC arm and 0.5% (1/217) in the placebo arm also developed neutralizing antibodies.

A total of 1454 (>99%) patients who received ACTEMRA-SC in the all exposure group have been tested for anti-tocilizumab antibodies. Thirteen patients (0.9%) developed antitocilizumab antibodies, and, of these, 12 patients (0.8%) developed neutralizing antibodies.

The rate is consistent with previous intravenous experience. No correlation of antibody development to adverse events or loss of clinical response was observed.

Laboratory Abnormalities Neutropenia During routine laboratory monitoring in the 6-month controlled clinical trials, a decrease in neutrophil count below 1 × 109/L occurred in 2.9% and 3.7% of patients receiving ACTEMRA-SC weekly and every other week, respectively.

There was no clear relationship between decreases in neutrophils below 1 x 109/L and the occurrence of serious infections.

Thrombocytopenia During routine laboratory monitoring in the ACTEMRA-SC 6-month controlled clinical trials, none of the patients had a decrease in platelet count to ≤ 50 × 103/mcL. Elevated Liver Enzymes During routine laboratory monitoring in the 6-month controlled clinical trials, elevation in ALT or AST ≥ 3x ULN occurred in 6.5% and 1.4% of patients, respectively, receiving ACTEMRA-SC weekly and 3.4% and 0.7% receiving ACTEMRA SC every other week.

Lipids During routine laboratory monitoring in the ACTEMRA-SC 6-month clinical trials, 19% of patients dosed weekly and 19.6% of patients dosed every other week and 10.2% of patients on placebo experienced sustained elevations in total cholesterol > 6.2 mmol/l (240 mg/dL), with 9%, 10.4% and 5.1% experiencing a sustained increase in LDL to 4.1 mmol/l (160 mg/dL) receiving ACTEMRA-SC weekly, every other week and placebo, respectively.

DRUG INTERACTIONS

Other Drugs for Treatment of Rheumatoid Arthritis Population pharmacokinetic analyses did not detect any effect of methotrexate (MTX), non-steroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance.

Concomitant administration of a single dose of 10 mg per kg ACTEMRA with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure.

ACTEMRA has not been studied in combination with biological DMARDs such as TNF antagonists [see Dosage and Administration].

Interactions with CYP450 Substrates Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with tocilizumab may restore CYP450 activities to higher levels than those in the absence of tocilizumab leading to increased metabolism of drugs that are CYP450 substrates. In vitro studies showed that tocilizumab has the potential to affect expression of multiple CYP enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Its effects on CYP2C8 or transporters is unknown. In vivo studies with omeprazole, metabolized by CYP2C19 and CYP3A4, and simvastatin, metabolized by CYP3A4, showed up to a 28% and 57% decrease in exposure one week following a single dose of ACTEMRA, respectively.

The effect of tocilizumab on CYP enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of ACTEMRA, in patients being treated with these types of medicinal products, therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) should be performed and the individual dose of the medicinal product adjusted as needed. Exercise caution when ACTEMRA is coadministered with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy [see Clinical Pharmacology].

Live Vaccines Avoid use of live vaccines concurrently with ACTEMRA [see Warnings and Precautions].

USE IN SPECIFIC POPULATIONS

Pregnancy Pregnancy Category C. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.

Risk Summary Adequate and well-controlled studies with ACTEMRA have not been conducted in pregnant women. In animal reproduction studies, administration of tocilizumab to cynomolgus monkeys during organogenesis caused abortion/embryo-fetal death at dose exposures 1.25 times the human dose exposure of 8 mg per kg every 2 to 4 weeks.

The incidence of malformations and pregnancy loss in human pregnancies has not been established for ACTEMRA. However, all pregnancies, regardless of drug exposure, have a background rate of 2 to 4% for major malformations, and 15 to 20% for pregnancy loss.

ACTEMRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations In general, monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester.

Animal Data An embryo-fetal developmental toxicity study was performed in which pregnant cynomolgus monkeys were treated intravenously with tocilizumab (daily doses of 2, 10, or 50 mg per kg from gestation day 20-50) during organogenesis. Although there was no evidence for a teratogenic/dysmorphogenic effect at any dose, tocilizumab produced an increase in the incidence of abortion/embryo-fetal death at 10 mg per kg and 50 mg per kg doses (1.25 and 6.25 times the human dose of 8 mg per kg every 2 to 4 weeks based on a mg per kg comparison). Testing of a murine analogue of tocilizumab in mice did not yield any evidence of harm to offspring during the pre-and postnatal development phase when dosed at 50 mg per kg intravenously with treatment every three days from implantation until day 21 after delivery (weaning). There was no evidence for any functional impairment of the development and behavior, learning ability, immune competence and fertility of the offspring.

Nursing Mothers It is not known whether tocilizumab is excreted in human milk or if it would be absorbed systemically in a breastfed infant after ingestion. IgG is excreted in human milk, and therefore it is expected that tocilizumab could be present in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ACTEMRA, 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 ACTEMRA by intravenous use is indicated for the treatment of pediatric patients with: • Active systemic juvenile idiopathic arthritis in patients 2 years of age and older • Active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older Safety and effectiveness of ACTEMRA in pediatric patients with conditions other than PJIA or SJIA have not been established. Children under the age of two have not been studied. SC administration has not been studied in pediatric patients. Testing of a murine analogue of tocilizumab did not exert toxicity in juvenile mice. In particular, there was no impairment of skeletal growth, immune function and sexual maturation.

Geriatric Use Of the 2644 patients who received ACTEMRA in Studies I to V [see Clinical Studies], a total of 435 rheumatoid arthritis patients were 65 years of age and older, including 50 patients 75 years and older. Of the1069 patients who received ACTEMRA-SC in studies SC-I and SC-II there were 295 patients 65 years of age and older, including 41 patients 75 years and older.

The frequency of serious infection among ACTEMRA treated subjects 65 years of age and older was higher than those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Hepatic Impairment The safety and efficacy of ACTEMRA have not been studied in patients with hepatic impairment, including patients with positive HBV and HCV serology [see Warnings and Precautions].

Renal Impairment No dose adjustment is required in patients with mild renal impairment. ACTEMRA has not been studied in patients with moderate to severe renal impairment [see Clinical Pharmacology].

OVERDOSAGE

There are limited data available on overdoses with ACTEMRA. One case of accidental overdose was reported in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia.

In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.

PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Medication Guide) Patient Counseling Advise patients and parents or guardians of minors with PJIA or SJIA of the potential benefits and risks of ACTEMRA. Physicians should instruct their patients to read the Medication Guide before starting ACTEMRA therapy.

• Infections: Inform patients that ACTEMRA may lower their resistance to infections. Instruct the patient of the importance of contacting their doctor immediately when symptoms suggesting infection appear in order to assure rapid evaluation and appropriate treatment.

• Gastrointestinal Perforation: Inform patients that some patients who have been treated with ACTEMRA have had serious side effects in the stomach and intestines. Instruct the patient of the importance of contacting their doctor immediately when symptoms of severe, persistent abdominal pain appear to assure rapid evaluation and appropriate treatment.

• Hypersensitivity and Serious Allergic Reactions: Assess patient suitability for home use for SC injection. Inform patients that some patients who have been treated with ACTEMRA have developed serious allergic reactions, including anaphylaxis. Advise patients to seek immediate medical attention if they experience any symptom of serious allergic reactions.

Instruction on Injection Technique Perform the first injection under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer subcutaneous ACTEMRA, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous ACTEMRA and the suitability for home use [See Patient Instructions for Use].

Prior to use, remove the prefilled syringe from the refrigerator and allow to sit at room temperature outside of the carton for 30 minutes, out of the reach of children. Do not warm ACTEMRA in any other way.

Advise patients to consult their healthcare provider if the full dose is not received.

A puncture-resistant container for disposal of needles and syringes should be used and should be kept out of the reach of children. Instruct patients or caregivers in the technique as well as proper syringe and needle disposal, and caution against reuse of these items.

ACTEMRA® (tocilizumab) Genentech USA, Inc., A Member of the Roche Group South San Francisco, California 94080-4990 Copyright © 2014 Genentech USA, Inc. All rights reserved. ACT/102714/0029

Cosmos Communications

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NORM 2014 Highlights

NORM Education Committee…Continued from the cover know we are in this together. We all struggle to meet the day-to-day requirements of managing a busy rheumatology practice. Time man­ agement is an essential skill set, and we must balance our various roles in order to make the best decisions for our offices.

It takes teamwork to educate staff members on the ever-changing healthcare landscape. What worked today in your practice may not work tomorrow. Knowing this, NORM leadership began to consider some commonly asked questions: How can we streamline processes to help prac­ tices become more efficient? How do we as administrators manage the newest biologics and therapeutic regi­ mens? Where can we locate the latest forms? All of these and other ques­ tions underscored the need for a tool to capture the answers that NORM members have shared, as well as a resource to develop and disseminate that tool to the greater membership.

Time management is an essential skill set, and we must balance our various roles in order to make the best decisions for our offices.

It takes teamwork to educate staff members on the ever-changing healthcare landscape.

What worked today in your practice may not work tomorrow.

An idea took shape: We needed a visual work tool, perhaps something that linked disease states to accepted

Exercising Recommendations Gentle exercise may help with fibromyalgia.

Walking

Water Aerobics

Online Education Portal “The goal for the education com­ mittee is to bring educational value to the NORM webpage for its mem­ bership—a place to go to find a quick answer,” Ms Byrnes said. “We all work hard to meet the demands of constant changes in the medical field, from Meaningful Use to ICD-

Biking

Check with your doctor before starting a new exercise plan.

Figure 1 Exercise recommendations for a patient with fibromyalgia.

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RHEUMATOLOGY PRACTICE MANAGEMENT

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decision pathways. The tool could serve as a platform to educate staff members on procedures and work­ flows, bringing together information gathered over years of experience.

This led the organization to create the NORM Education Committee (NEC), led by Lynette Byrnes, com­ mittee chairperson, to spearhead the development of an educational resource tool.

“It took a village of administrators to create these robust tools,” Ms Byrnes said. She leads the committee with co-chairperson Andrea Zlatkus and their team: Theresa Arlen, Christine Mann, Colleen Taylor, SaVonna Staton, and Judith Stovall.

“I was so thrilled to see the responses from volunteers in the membership to help with this endeavor. It was an honor to work with my fellow col­ leagues. When the me turns into we, what is created is amazing.”

NEC members bring various back­ grounds to the committee, includ­ ing experience with small and large practices as well as in-house and outsourced billing procedures; they also represent practices with infu­ sion suites, radiology services, and in-house laboratories. This collabo­ rative effort creates a powerful team.

NORM’s goal was, and continues to be, membership engagement; the NEC is no different. Committee members came together, sharing their knowledge and pearls of wis­ dom to develop a tool that captures best practices.

NORM 2014 Highlights

10. This is where the need to cre­ ate an educational portal came into play. Having these dynamic tools as a resource can lessen the administra­ tive burden placed on practices on a daily basis.”

The NEC Education Portal Project quickly evolved into 2 sep­ arate PowerPoint presentations, encompassing a plethora of infor­ mation. The material was divided into a Practice Workflow Tool and Rheumatology Disease Workbook.

The Workflow Tool contains a robust program that takes staff members through daily procedures such as Check-In, Evaluation and Management, Ancillary Care, Billing, and Checkout. The website provides users with links that con­ nect to the latest information. The Workbook increases the knowledge of new and existing staff members, giving them a basic understanding of rheumatologic diseases that phy­ sicians treat on a daily basis (Figure 1). The Workbook also lists drugs and biologics commonly used in the treatment of these diseases, with links to pharmaceutical websites for additional information (Figure 2).

These 2 presentations were designed to serve as a tool to train staff members and empower them to create strong procedures and checklists. In addition, users can review their own in-house processes and use NEC-suggested guidelines to accommodate specific practice needs. An Office Forms sec­ tion allows users to retrieve forms that have been shared on the Listserv by NORM members. In the future, the Educational Portal will also contain the following sections: Meaningful Use, ICD-10, Human Resources, NEC News, and Hot Topics.

Priceless Membership Benefits Annual membership in NORM provides access to these powerful tools. Whether an existing employee needs a refresher on a billing matter,

Treatment Continued Approved Biologics

Enbrel - for company’s website click here Remicade - for company’s website click here Kineret - for company’s website click here Humira - for company’s website click here Orencia - for company’s website click here Rituxan - for company’s website click here Actemra - for company’s website click here Simponi - for company’s website click here Simponi ARIA - for company’s website click here Cimzia - for company’s website click here Xeljanz - for company’s website click here

Figure 2 Resource page regarding biologics used to treat rheumatologic diseases.

or a new hire needs a run-down of a process checklist, the NEC has it covered. The committee has worked hard to include all key informa­ tion in the Education Portal and to

ous subject matters to enhance the NEC portfolio.

We hope that members find these tools beneficial. If you have a topic that you would like to see devel­

“The goal for the education committee is to bring educational value to the NORM webpage for its membership—a place to go to find a quick answer. We all work hard to meet the demands of constant changes in the medical field.”

— Lynette Byrnes, Chairperson, NORM Education Committee

focus on specific problem areas in an effort to fulfill all of a practice’s needs. This project will continue to evolve to meet the ever-chang­ ing needs of practice management; NEC is committed to bringing the latest information to its members, and will reach out to the NORM membership for expertise in numer­

December 2014

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oped, or if you would like to share your know-how in a particular sub­ ject area, please contact an NEC member, whose e-mail addresses are on the NEC webpage (available through www.normgroup.org). Log onto the members-only page dropdown and select Education for more information. l

www.RheumatologyPracticeManagement.com

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NORM 2014 Highlights

OSHA Compliance: Tips Offered for Rheumatology Offices

By Rosemary Frei, MSc

R

heumatology managers re­ cently received expert tips and updates on Occupational Safety & Health Administration (OSHA) compliance standards, as well as how to prepare a medical practice for an OSHA inspection.

Bill Fivek, President and CEO of Total Medical Compliance, dis­ cussed these government-mandat­ ed requirements at the National Organization of Rheumatology Managers (NORM) annual confer­ ence, held September 12-13, 2014, in Louisville, KY. Mr Fivek emphasized that compli­ ance involves more than just train­ ing. The most important step, he said, is ensuring that management teams understand the significance of adhering to OSHA guidelines and train employees as required.

“If the top folks do not believe in the program, no one else is going to follow it,” he said. “Your physicians sometimes may balk at OSHA. They think it’s another example of government getting in the way of them practicing medicine. But it’s the law. It’s not something you can get around, and ultimately the practice is held responsible for the performance of its employees.”

The Bloodborne Pathogens Standard of 1991 is a key element of OSHA as applied to clinical practices, he said.1 Main require­ ments include having a written exposure-control plan, providing a hepatitis B vaccination series of 3 shots—at no cost to employees—to all those who could be exposed to the virus in the workplace, having labels and signs to communicate hazards, providing personal protec­ tive equipment, and enforcing work practice controls.

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“Make sure you have a hepatitis B vaccination certificate, nonre­ sponder documentation or declina­ tion form on file for every employ­ ee. These are the most common violations in an OSHA inspection,

Clinics must provide employees who may be exposed to pathogens with the appropriate personal protective equipment at no cost to the employees.

when people cannot produce this information, especially with new employees,” Mr Fivek said. “But note that ‘employee’ is an operative word. If your physicians own the practice, they’re not employees and therefore OSHA doesn’t apply to your physicians.”

Clinics also must provide employees who may be exposed to pathogens with the appropri­ ate personal protective equipment (PPE) at no cost to the employ­ ees. The staff person responsible for OSHA compliance determines which PPE is required, Mr Fivek said. Furthermore, it is important to comply with the Needlestick Safety and Prevention Act of 1991 and updates that came into effect in 2001 requiring an annual evalua­ tion of safer sharps devices.1 “Anything that’s considered to be a sharp in your practice needs to

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be evaluated to see whether there’s a safety sharp version of it avail­ able—if you use a scalpel, if you use needles, I think in your line of work they probably are the extent of your sharps,” noted Mr Fivek. “Go to your vendors that you get your supplies from every 12 months and ask them, ‘Are there safety devices available for these items?’ Get some samples.”

Ask people in the practice to give feedback on the samples, and make purchase decisions based on that feedback, advised Mr Fivek. OSHA requires that practices document this effort, and also that they docu­ ment if a safety sharp is unavailable or will endanger patients or employ­ ees if it is used. It also is impor­ tant to always activate the safety device before placing equipment into a sharps container and to use other engineering controls that are available for additional protection against sharps exposure.

If an exposure does occur, the affected individual should attempt to clean the contaminated part of his or her body and immediately report the incident to the employer.

The employer should direct the employee to a healthcare profes­ sional for testing for hepatitis B and C and for HIV, and to provide the healthcare professional with docu­ mentation of the details of the inci­ dent. After testing, the healthcare professional and the employer must communicate with each other and the employee about follow-up steps.

These procedures should be set out in advance.

“With needle sticks, your win­ dow of opportunity is 1 hour, 2 at the most, to start any kind of post­ exposure prophylaxis for an HIV

NORM 2014 Highlights

exposure. Hepatitis B you can do up to 14 days later, while hepatitis C has no postexposure prophylaxis procedure,” Mr Fivek said. “And you need to make sure you have a facility that’s going to be open when you are, that’s going to do that kind of blood-panel testing, and can do rapid HIV testing.”

The employer must train employ­ ees regarding exposure procedures at no cost to the employee and during work hours—with an oppor­ tunity for interactive questions and answers with the instructor—first when the person is assigned to a task where exposure may occur and then every year after that. In addition, training must be carried out within 90 days of the effective date of any change in an OSHA standard. Records of training must be kept for 3 years. Confidential medical records are also required for employees who are at risk of exposure to bloodborne pathogens, which need to be retained for the duration of the person’s employ­ ment plus 30 years.

OSHA made a rare change to the regulations in 2012, said Mr Fivek, involving hazard communi­ cation.2 As of December 1, 2013, all employees must be trained in the regulations, with full compliance by June 1, 2016, including the follow­ ing: the creation of a hazard com­ munication plan; the creation and annual maintenance of an inven­ tory of hazardous materials; the cre­ ation of a set of standardized Safety Data Sheets that include 8 colorcoded, standardized pictograms; labeling of secondary containers of hazardous materials; and ensuring there is appropriate PPE based on the employees’ chemical use.

“All of the OSHA inspections that we have gotten pulled in to work on with our clients, the OSHA

inspector has asked where the Material Safety Data Sheet book is.

Make sure everyone on staff, as part of your new hire orientation, knows where it is,” advised Mr Fivek. He said that some of the additional OSHA requirements are the follow­ ing: flush eyewash stations weekly to reduce bacterial growth in the water reservoirs; develop a written

The employer must train employees regarding exposure procedures at no cost to the employee and during work hours… first when the person is assigned to a task where exposure may occur and then every year after that. fire response plan (only for practices with more than 10 employees) that stipulates such things as evacuating patients rather than fighting the fire; and regular inspections of elec­ trical plugs, sockets, and breaker boxes, and of gas cylinders.

OSHA compliance checklists are available from Total Medical Compliance and many other places including the OSHA website.3 If an OSHA inspector visits your practice it will usually be without notice and for 1 of 5 reasons, said Mr Fivek: “There was a complaint lodged against the practice by an employ­ ee or another government agency; something in the practice could cause death or serious physical

December 2014

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harm; random inspection; there has been an incident in which 3 or more employees were hospitalized or someone died; or it is a follow-up inspection to ascertain whether a problem has been rectified, in which case the inspector could levy a daily fine until the problem is corrected.”

It is important to stay calm and to ask the inspector for identification and for the reason for the visit. Staff can use that time—but no more than 15 minutes—for a quick check of the practice, advised Mr Fivek.

“While you’re verifying their cre­ dentials, you’ve got someone else running around the practice mov­ ing all the paper coffee cups away from places they shouldn’t be, mov­ ing the Christmas decorations away from the breaker box, and fixing other things that could get you in trouble.” Then the OSHA employ­ ee will conduct a walk-through, followed by a closing conference in which the inspection findings are discussed. Fivek said examples of citations by OSHA include not providing necessary protective equipment and not having direc­ tion arrows on exit signage.

“You have a right to contest any of the inspector’s findings with no risk of things being worse due to your push-back,” noted Mr Fivek.

“Always ask for any appropriate reductions in fines. It can be a scary process, but they’re pretty easy to work with.” l

References

1. Occupational Safety & Health Administration.

Revisions of OSHA’s Bloodborne Pathogens Standard. Technical Background and Summary. www.osha.gov/needlesticks/needlefact.html. Accessed November 18, 2014.

2. Occupational Safety & Health Administration. www.osha.gov/pls/oshaweb/owadisp.show_doc ument?p_table=STANDARDS&p_id=10099.

Accessed November 18, 2014.

3. Occupational Safety & Health Administration.

Small Business Handbook. www.osha.gov/Publi ­c ations/smallbusiness/small-business.html#check.

Accessed November 18, 2014.

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NORM 2014 Highlights

Getting the Best from Your Medical Group

By Rosemary Frei, MSc

R

heumatology managers re­ cently received practical ad­ vice on how to cultivate opti­ mal interpersonal working conditions as well as maintain healthy and productive relationships while work­ ing in medical group practices. At the National Organization of Rheumatology Managers (NORM) 2014 Annual Conference, Wayne Sotile, PhD, founder of the Sotile Center for Resilience and the Center for Physician Resilience in Davidson, NC, discussed these common con­ cerns as well as ways to address burn­ out and how to keep medical team members satisfied with their jobs.

According to Dr Sotile, this in­ volves paying close attention to one’s own behavior, and learning to behave in a way that leads others to bring out the best in themselves, creating a safe place for people. He pointed out that workplace condi­ tions that involve high demand as well as low autonomy and team sup­ port are strongly associated with ca­ reer dissatisfaction.

“When you start stripping an indi­ vidual’s sense of control, people start getting cranky,” Dr Sotile said. “Then we have the greatest risk of all, rela­ tive to resilience, and that is when we turn on each other. We start creating those ‘us–them,’ ‘we–they’ ways of thinking that we’re infinitely capable of. The front office, the back office, this subspecialty, and that subspecial­ ty,” observed Dr Sotile.

The remedy is for the practice’s leader to create a safe space for oth­ ers, drive accountability, and curb inappropriate workplace behaviors, he said.

“Do whatever you can do to boost actual and perceived support and con­ trol, for yourself and other people,” said Dr Sotile. “And curb not only aggressive, but passive and passive-ag­

gressive resistance to dynamic collab­ oration and collegiality. That way you increase the odds that you’re going to lead effectively and you increase the odds you’re going to cope effectively.”

He noted that most physicians are very dedicated to their professions; however, the flip side is overwork and burnout. Three times as many physicians compared with members of other professions work at least 60 hours a week, with 22% of practi­ tioners working more than 80 hours a week. In addition, 46% of physi­ cians are burned out, as well as about half of internists, according to a study he cited.1 Burnout and psychosocial distress are the most pervasive and un­ checked risks to work safety, quality, and satisfaction. There is a link be­ tween burnout and higher rates of medical errors and medical malprac­ tice suits, and lower patient compli­ ance and patient satisfaction.2 “There’s a universal rule that ap­ plies to a lot of high-performing people—we learn well how to prac­ tice our profession but we don’t learn how to live our lives as busy people.

Mismanaging our work-life challeng­ es and our personal coping style leads to burnout, and physician burnout is the biggest risk factor for disillusion­ ment of the medical professionals’ family members,” stated Dr Sotile.

He uses the Myers-Briggs Type Indicator and 360 Evaluation assess­ ments to help alleviate these diffi­ culties. These systems help people understand themselves better and gain insight into why they might find it challenging to interact with some individuals.

He also emphasized the importance of honestly assessing oneself and one’s strengths and weaknesses with respect to the work environment.

“There is a place for quitting a job,

there is a place for leaving a relation­ ship. But the next one you’re in, you’re going to have to face the same journey,” observed Dr Sotile. “I know a physician who is getting his fifth board certification, looking for that perfect organization, that per­ fect specialty. At some point you’ve got to say, ‘Look, there are no perfect people.’ When the interpersonal conflict heats up, that’s the time to demonstrate your character.”

This points to a need to adjust to different personalities and to man­ age change. Managing change sus­ tainably requires pitching new ideas or courses of action relative to each person’s sense of autonomy, mas­ tery, and purpose, said Dr Sotile.

“Most often, we try to motivate others by telling them what to do; through verbal persuasion we ex­ plain why they should do something.

The problem with that is unless the other people can each answer these questions—‘Is it worth it relative to what I value?’ and ‘Am I going to be able to do this?’—the verbal persua­ sion just sounds like attacking, bully­ ing, nagging, and blaming,” noted Dr Sotile. “The most powerful ways of getting people to change are getting them to try a new way of doing things so they see that they can do it, and to tell them stories that illustrate how the change will be beneficial or going where you’re trying to lead.”

Frequent, immediate, relevant, and positive reinforcement is necessary to sustain change and engagement, and must be contingent on something.

This is tied in with making a practice a safe place for someone else, and can be accomplished in less than 20 sec­ onds. Giving a compliment or words of admiration and appreciation can go a long way toward making others feel safe and valued.

He noted it is also important to Continued on page 20

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I December 2014

Quality Metrics

Measuring Quality Improvement…Continued from the cover practice administrators fight the fight each day.

The Realities of the Industry The healthcare industry is moving in a direction that concerns admin­ istrators, physicians, and patients alike. Reducing healthcare costs needs to be addressed, but whether the right people are addressing the issues remains to be seen.

As with other administrators, I find myself fighting with insurance plans about coverage for patients on a daily basis. When our clinical staff speaks to insurance plans on behalf of our patients, most of the time the insurance person responding is read­ ing a prompt on a computer screen written by an insurance carrier that never handled a patient in a clinical setting. Are we the only industry that handles business this way? I challenge you to point to another industry where its providers or busi­ ness owners are expected to take a back seat to receiving payment for services at the time services are provided.

In rheumatology, we also face the issue of quality improvement tracking. Companies are working to develop online data centers that would allow rheumatologists to track 1 or more quality measures in a specific subset of patients—such as patients with rheumatoid arthritis (RA)—for each patient encounter.

Getting Out of the Routine Finding innovative ways to track patients may seem daunting at first, especially with everything else we do as practice administrators.

However, learning more about the different programs available and lis­ tening to providers who use these programs can be an eye-opening experience. At our practice, we

have spent hundreds of thousands of dollars on our electronic medical record technology; however, it does not have a general overview screen, for example, with patients’ status that can quickly tell you how a spe­ cific group of patients, such as those with RA, are doing.

When our clinical staff speaks to insurance plans on behalf of our patients, most of the time the insurance person responding is reading a prompt on a computer screen written by an insurance carrier that never handled a patient in a clinical setting. Are we the only industry that handles business this way?

We have all fallen into a routine of seeing a new patient diagnosed with RA, and then scheduling that patient for a follow-up visit 3 to 4 months later—on a recurring basis—for the rest of their lives.

Because we are comfortable with this routine, we sometimes forget that not every patient with RA needs to be seen by his or her rheu­ matologist every 3 to 4 months.

The patient may have declined sug­ gested treatment, the patient may

December 2014

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be stable, or the patient may be in remission.

Why do we schedule a follow-up appointment so quickly after a visit?

This routine affects our schedules because it takes time away from patients who need it the most, including our severely ill patients with RA as well as those who do not respond to their medication.

Focusing on Quality Care Rheumatologists need to look at their practice as a whole, on a regular basis (monthly, daily), and be aware of laboratory tests and other measures of quality, such as the Routine Assessment of Patient Index Data (RAPID) 3 assessment or the Multidimensional Health Assessment Questionnaire (MD-HAQ). They may not real­ ize how many uncontrolled RA patients they have. Start by attempt­ ing a guess at the number of patients in your practice who you believe have their RA under control, and then look at the actual numbers.

These data may be surprising…and eye-opening.

We track quality measures with the Physician Quality Reporting System (PQRS) and Meaningful Use. There is a shift from the fee-for-service model to quality improvement outcomes. How or when we will make this shift fully is the unknown, but now is the time to start rethinking the way we monitor and track patient out­ comes. After attending a seminar recently on this subject, I saw this in a whole new light, and it has begun a conversation in our practice about how we approach the inevitable: the future of being paid not as a fee for service, but based on the quality improvements we provide for our patients. l

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Meaningful Use

What Meaningful Use Means…Continued from the cover Checklist 1. Meaningful Use 2014 Stage 1 Core Measures4 ✓ Computerized provider order entry (CPOE) ✓ E-prescribing (eRx) ✓ Implement a clinical decision support rule ✓ Provide patients with the ability to view, download, or transmit their health information or hospital admission information online ✓ Provide clinical summaries for patients for each office visit ✓ Allow for drug–drug interaction and drug allergy checks ✓ Record demographics information ✓ Maintain an up-to-date problem list of current and active diagnoses ✓ Maintain an active medication allergy list ✓ Maintain an active medication list ✓ Record and chart changes in vital signs ✓ Record smoking status for patients aged ≥13 years ✓ Protect electronic health information

Checklist 2. Meaningful Use Stage 1 Menu Measures4 ✓ Implement drug formulary checks ✓ Incorporate clinical lab test results into EHR as structured data ✓ Generate lists of patients by specific conditions ✓ Send reminders to patients per patient preference for preventive/follow-up care ✓ Use certified EHR technology to identify patient-specific education resources and provide to patient, if appropriate ✓ Perform medication reconciliation, when necessary ✓ Summary of care record for each transition of care/referrals ✓ Ability to submit electronic data to immunization registries/systems ✓ Ability to submit electronic syndromic surveillance data to public health agencies

as quality, safety, and efficiency. End results of Meaningful Use implemen­ tation, such as better clinical out­ comes, empowered patients, as well as the strength of research data on US health systems, may be part of the explanation.

Meaningful Use, in more com­ mon terms, could be described as a way for healthcare providers to show the Centers for Medicare & Medicaid Services (CMS) that they have meaningfully used their certified

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EHRs, and that they have met the objectives that CMS established for relevant stages of Meaningful Use within a specified time period to receive Medicare incentive payments.

The most important question, though, is how do you describe it? In these times of reimbursement cuts and rising expenses, what role does it play in your day-to-day practice? Perhaps it is another curveball, or more objec­ tives and requirements to comply with in order to receive payment from the

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I December 2014

federal government over a 5-year peri­ od for the excellent job your staff and physicians do every day.

Regardless of how you explain Meaningful Use, the stages and compliance expectations are clear.

A visit to the CMS webpage, plus a few clicks through the Regulations and Guidance1 and EHR Incentive Programs pages will bring up a menu of information and links to learn more about the incentive programs as well as Meaningful Use.2 To become eligible to receive EHR incentive payments, your first step is to get certified EHR technology (CEHRT). Many programs allow you to electronically enter patients’ med­ ical information, but also have other capabilities that have the potential to improve patient care. Once you have an EHR, you then want to make sure you are eligible to participate.

Eligible professionals who can partic­ ipate in the Medicare EHR Incentive Program are as follows3: • Doctors of medicine or osteop­ athy • Doctors of dental surgery or den­ tal medicine • Doctors of podiatry • Doctors of optometry • Chiropractors.

Once you register for the pro­ gram, you then must perform the requirements for Meaningful Use and “attest,” or report to CMS. The amount of your incentive payment depends on when you begin to par­ ticipate. You will receive 75% of your Medicare allowable charges up to a maximum annual cap. Under man­ datory sequestrations as of March 1, 2013, Medicare EHR incentive payments to all eligible professionals have been reduced by 2%.2 If you demonstrated Meaningful Use and received a Medicare EHR incentive payment in 2011 or 2012, you are eligible to receive the maximum incentive payment of

Meaningful Use

approximately $44,000 per eligible provider over 5 consecutive years of participation. If you have not started the program in 2014, you are not eligible to receive any incen­ tive payment under the Medicare EHR Incentive Program. Eligible professionals who do not meet the requirements for Meaningful Use by 2015 will be penalized via potential reductions in their Medicare reim­ bursements.3 These will start at 1% each year and reach a maximum of 5% annual adjustments by 2020.

Meaningful Use is broken down into stages. Stage 1 begins the first year of participation and contin­ ues for 2 years. Eligible professionals must report data on a continuous 90-day period during the calendar year; during the remaining years of participation, eligible profession­ als must meet requirements for the entire calendar year. These are called reporting periods. Providers must also meet certain other requirements in order to receive payment. There are no partial payments.

Stage 1 Eligible professionals demonstrat­ ing Stage 1 in 2014 must meet 13 core measures. Note that there are some exclusions, in limited circum­ stances, that could exempt providers from having to meet these require­ ments. Otherwise, you must report on all 13 core measures and meet the thresholds established (Checklist 1).4 As part of Stage 1, you also must report on 5 of 9 available menu measures (Checklist 2). In addition you must report on 9 recommended Clinical Quality Measures (CQMs)5; the data are calculated by your certi­ fied EHR (Checklist 3). You enter the data exactly as your certified EHR produced it.

Stage 2 CMS extended Stage 2 of the Meaningful Use program for an additional year through 2016 and

Checklist 3. 2014 Adult Recommended Clinical Quality Measures5 ✓ Controlling high blood pressure ✓ Use of high-risk medications in the elderly ✓ Preventive care and screening: tobacco use—screening and cessation intervention ✓ Use of imaging studies for low back pain ✓ Preventive care and screening: screening for clinical depression and follow-up plan ✓ Documentation of current medications in the medical record ✓ Preventive care and screening: body mass index (BMI) screening and follow-up ✓ Closing the referral loop: receipt of specialist report ✓ Functional status assessment for complex chronic conditions

Checklist 4. Meaningful Use 2014 Stage 2 Core Measures7 ✓ Use computerized provider order entry (CPOE) ✓ Generate and transmit prescriptions electronically (eRx) ✓ Record the demographic information ✓ Record and chart changes in specified vital signs ✓ Record smoking status for patients aged ≥13 years ✓ Use clinical decision support to improve performance on high-priority health conditions ✓ Provide patients the ability to view online, download, and transmit their health information ✓ Provide clinical summaries for patients ✓ Protect electronic health information created or maintained by certified EHR technology (CEHRT) ✓ Incorporate clinical lab-test results into CEHRT as structured data ✓ Generate lists of patients by specific conditions ✓ Use clinically relevant information to identify patients who should receive reminders for preventive/follow-up care ✓ Use clinically relevant information from CEHRT to identify patientspecific education resources ✓ Perform medication reconciliation as necessary ✓ Provide a summary care record for each transition of care or referral ✓ Have ability to submit electronic data to immunization registries or immunization information systems ✓ Use secure electronic messaging to communicate with patients

postponed the start of Stage 3 until 2017. CMS admitted to problems with CEHRT and its implemen­ tation, which contributed to the

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agency’s decision. The earliest that Stage 2 criteria are effective is 2014.6 For 2014 only, all providers regard­ Continued on page 20

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Meaningful Use

What Meaningful Use Means…Continued from page 19 Checklist 5. Meaningful Use Stage 2 Menu Measures7 ✓ Ability to submit electronic syndromic surveillance data to public health agencies ✓ Record electronic notes in patient records ✓ Make imaging results accessible through CEHRT ✓ Record patient family health history as structured data ✓ Ability to identify and report cancer cases to a public health central cancer registry ✓ Ability to identify and report specific cases to a specialized registry (other than a cancer registry)

less of their stage of Meaningful Use are only required to demonstrate Meaningful Use for a 3-month EHR reporting period. It is fixed to a quar­ ter of the calendar year that aligns with existing CMS quality measure­ ment programs, such as the Physician Quality Reporting System (PQRS).

CMS will only allow their 1-time, 3-month reporting period in 2014 so that all providers who must upgrade to 2014 CEHRT will have adequate time to implement their new CEHRT systems.6

Stage 2 Meaningful Use Criteria Eligible professionals must meet 17 core measures as well as 3 menu measures that they select from a total list of 6 (Checklists 4 and 5). This equals a total of 20 core measures.7 In 2014, all eligible providers, regard­ less of their stage of participation in Meaningful Use, are required to

report on CQMs in the same way; they must report on 9 recommended CQMs (Checklist 3).

In addition, all providers must select CQMs from at least 3 of the 6 key healthcare policy domains rec­ ommended by the US Department of Health & Human Services National Quality Strategy. These include the following: (1) patient and fam­ ily engagement, (2) patient safety, (3) care coordination, (4) popula­ tion and public health, (5) efficient use of healthcare resources, and (6) clinical processes/effectiveness.

All Medicare-eligible providers who are beyond their first year of reporting are required to report their CQM data electronically to CMS. Eligible professionals can electronically report CQMs either individually or as a group.8

Conclusion However you choose to explain

Meaningful Use—and regardless of what it means to you and your prac­ tice—the expectations regarding adherence are clear. We as practice administrators learn to wear many hats, and, as we move toward 2015, we will stay ready for whatever the next curveball may be. l

References

1. Centers for Medicare & Medicaid Services.

Regulations & guidance. www.cms.gov/Regulationsand-Guidance/Regulations-and-Guidance.html.

Accessed November 18, 2014.

2. Centers for Medicare & Medicaid Services. EHR incen­ tive programs. www.cms.gov/Regulations-and-Guidance/ Legislation/EHRIncentivePrograms/index.html. Updated October 7, 2014. Accessed November 18, 2014.

3. Centers for Medicare & Medicaid Services. Medicare Electronic Health Record incentive payments for eligible professionals. www.cms.gov/Regulations-and-Guidance/ Legislation/EHRIncentivePrograms/Downloads/MLN_ MedicareEHRProgram_TipSheet_EP.pdf. Updated May 2013. Accessed November 18, 2014.

4. Centers for Medicare & Medicaid Services. Eligible Professional Attestation Worksheet for Stage 1 of the Medicare Electronic Health Record (EHR) Incentive Program. www.cms.gov/Regulations-and-Guidance/ Legislation/EHRIncentivePrograms/Downloads/ EP_Attestation_Stage1Worksheet_2014Edition.pdf.

Accessed November 18, 2014.

5. Centers for Medicare & Medicaid Services. An introduction to EHR incentive programs for eligible professionals: 2014 clinical quality measure (CQM) electronic reporting guide. www.cms.gov/Regulationsand-Guidance/Legislation/EHRIncentivePrograms/ Downloads/CQM2014_GuideEP.pdf. Updated Sep­ tember 2014. Accessed November 18, 2014.

6. Centers for Medicare & Medicaid Services. Stage 2. www.cms.gov/Regulations-and-Guidance/Legislation/ EHRIncentivePrograms/Stage_2.html. Updated No­ ­ vember 5, 2014. Accessed November 18, 2014.

7. Centers for Medicare & Medicaid Services. Stage 2 Eligible Professional (EP) Meaningful Use core and menu measures table of contents. www.cms.gov/Regulationsand-Guidance/Legislation/EHRIncentivePrograms/ Downloads/Stage2_MeaningfulUseSpecSheet_ TableContents_EPs.pdf. Published October 2012.

Accessed November 18, 2014.

8. Centers for Medicare & Medicaid Services.

2014 Clinical Quality Measures. www.cms.gov/ R egulations-and-Guidance/Legisl a tio n/EHR IncentivePrograms/2014_ClinicalQualityMeasures. html. Accessed November 26, 2014.

Getting the Best from Your Medical…Continued from page 16 provide constructive performance feedback and to stop disruptive behav­ ior as quickly as possible. These are key to driving accountability and moving everyone to a high level of both pas­ sion for work and organizational iden­ tification, observed Dr Sotile.

“Any behavior that detracts from

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the mission and the performance needs to be addressed,” Dr Sotile said. “What dynamic leaders have to do is find that sweet spot of inner truth-teller but respectfully deliver the truth with no doubt being re­ lentless about the truth as it affects the organization. You don’t get

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what you want by focusing on what you don’t want.” l

References

1. Shanafelt TD, Boone S, Tan L, et al. Burnout and satisfaction with work-life balance among US physicians relative to the general US population. Arch Intern Med. 2012;172:1377-1385.

2. Wallace J, Lemaire J, Ghali WA. Physician wellness: a missing quality indicator. Lancet.

2009;374:1714-1721.

Don’t Face the Maze of Changes in Rheumatology Alone

NORM Keeps You Informed National Organization of Rheumatology Managers

NORM’s mission is to provide rheumatology managers, administrators and managing physicians countless opportunities to network with colleagues through our listserv and annual conference.

At NORM, our goals involve addressing, educating, distributing, and functioning as a conduit for rheumatologic practice management needs and expertise.

“NORM, by far, surpasses the benefits of any other organization I have ever belonged to. Through the listserv, NORM members willingly assists each other by providing solutions to everyday issues that arise while managing a rheum practice. We share experiences, ideas, protocols and procedures specific to a rheumatology practice. The annual NORM conference in September is definitely the icing on the cake as we all come away with practical ideas and tools we can implement.” Mary Jo Wideman, RN, BSN, Practice Manager

Do you have questions about coding, biologics, insurance carrier denials or personnel issues? Join NORM to help find your answers. Are your questions state specific, MAC specific or national coverage issues? NORM offers rheumatology managers the opportunity to connect across the Nation. Through our listserv you receive expert advice from professionals in rheumatology!

Join NORM and network with experienced managers through our listserv, gain access to our members only section which contains sample practice forms, job descriptions, and other documents that have been shared on this listserv, a list of our members, and in the future educational resources. NORM also hosts webinars throughout the year to continue supporting the education of our members.

Membership is open to rheumatology professionals including physicians and those who hold a management position in a rheumatology practice.

Save the Date for our 2015 2014 Annual Conference September 12 18 & 13, 19, 2014 2015 ~ Louisville, Bellevue, WA KY

NORM ~ www.normgroup.org ~ info@normgroup.org

Human Resources

Tattletale or Whistleblower: What’s an Employer to Do?

By Robert D. Orzechowski, MBA, SPHR

A

quick review of the eve­ ning news will often reveal stories of someone in an organization either doing wrong or blowing the whistle on some­ one else who did wrong. No orga­ nization is immune from having its reputation questioned when an employee or manager is caught violating ethical or legal standards, and the fallout can be damaging in many ways.

We read almost daily about deliberate misdeeds, illegal behav­ iors, or unethical acts. Many of these behaviors have come to light because a current or former employ­ ee felt that pursuing corrective actions via internal avenues would be ineffective. Yet many people also remain silent out of fear of retalia­ tion. When the wrongdoing is ulti­ mately revealed, this act is referred to as “whistleblowing.”

In certain cases, whistleblowing can be profitable. In a recent medi­ cal billing case in Kentucky, a phy­ sician was awarded $283,412.90 as part of a settlement.1 Some elements of this case and its settle­ ment fell under the whistleblow­ er provisions of the federal False Claims Act, which allows private citizens with knowledge of fraud to bring civil actions on behalf of the United States, and to share in any recovery.1 In other organizations (business­ es, nonprofits, and government, small or large) opportunities exist daily for people to choose whether to behave in a legal and ethical manner. Those who choose not to usually have a financial need, an opportunity (access to cash, data, or other company assets), and a rationalization for their behavior.

It is common to wonder why people make unethical or illegal

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choices, rather than adhere to the laws, regulations, and rules of com­ mon decency in their working lives.

Another question, however, may be equally as relevant: Why do those who have knowledge of such acts remain silent? A recent National Business Ethics Survey found that about one-third of workers who witness misconduct do not report it.2 So, what is an employer to do?

High retaliation rates will damp­ en reporting and increase the likeli­ hood that wrong behavior remains undiscovered. As such, there are tactical responses to the abovemen­ tioned question, keeping in mind that good tactics can never com­ pensate for a bad strategy. The real challenge is to create a culture of ethical decision-making and behav­ ior. Some suggestions to achieve this are presented below, and should only be implemented with the sup­ port of your upper management team. They include the following: • Manifest the organization’s posi­ tion on ethical behavior through all available forms of communica­ tion; written standards are impera­ tive. Meetings at all levels serve to maintain an aura of transparency, and can set an example for ethical expectations.

• Train everyone on standards and

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I December 2014

relevant topics for the organiza­ tion’s sphere of operations, and provide a resource for employees to turn to, such as a specific exec­ utive or human resources leader.

• Promulgate a policy and position for everyone to sign. Include a process for internally expressing concerns about suspected or wit­ nessed questionable behavior. An ethics or “whistleblower” hotline can be especially valuable. All pol­ icies should receive legal review, address the company’s position and standards clearly, provide examples of prohibited behavior and for reporting possible viola­ tions, and clearly prohibit retali­ ation against anyone who reports possible violations.

• Include in staff performance appraisals and job descriptions a section on level of compliance with company policies. Employee surveys can also support a compli­ ance effort.

• Clarify sanctions for all violators.

Ethical behavior necessarily deals with the vagaries of human life, and it is important to remain flexible enough to account for vari­ ety and unexpected possibilities in the working world. Providing clear expectations, support, and process­ es to achieve an ethical culture is the real challenge for any organi­ zation seeking to create and sustain an engaged workforce. Executives, owners, and human resources pro­ fessionals are especially suited to lead such efforts. l

References

1. The United States Attorney’s Office, Western District of Kentucky. Owners of Elizabethtown ­ Hematology Oncology, PLC agree to pay over $3.7 ­ ­ million to settle false billings to government health c­are programs. www.justice.gov/usao/kyw/news/­ ­ 2014/20140603-03.html. Accessed November 10, 2014.

2. Ethics Resource Center. National business ethics survey of the US workforce. www.ethics.org/downloads/2013 NBESFinalWeb.pdf. Accessed November 6, 2014.

Invitation to Join the RPM Editorial Board The publishers of Rheumatology Practice Management™ (RPM) are inviting qualified rheumatology practice owners and administrators to participate as members of the RPM Editorial Board. As an Editorial Board member, you will play an active role in helping to shape the content of this exciting new publication.

Rheumatology Practice Management is a niche publication focused on process solutions for rheumatology practices. RPM is designed to provide the rheumatology care team—medical, practice administrators, coders, and billers—with the knowledge and skills required to keep abreast of today’s fast-changing business environment, allowing practice professionals more time to concentrate on high-quality patient care. Each issue of RPM will focus on various areas of rheumatology practice, featuring current topics such as: • Healthcare technology • Models of care • Staffing • Reimbursement and coding • Drug updates

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Rheumatology Practice Management™ 1249 South River Road, Suite 202A, Cranbury, NJ 08512

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Rheumatoid Arthritis

Autoantibodies in Patients with RA Could Lead to More Precise Diagnosis, Therapy

By E. K. Charles

A

utoantibodies are a key fea­ ture of rheumatoid arthritis (RA) and a useful marker in the diagnosis and classification of the disease, as well as to determine its severity and development.

Previous research indicates that they may play an important role in the pathophysiology of RA. In an effort to assess the relationships between antibodies against carbamy­ lated protein (anti-CarP) antibodies, anticitrullinated protein antibodies (ACPA), genetic factors (HLADRB1 alleles and PTPN22), and smoking in RA, Xia Jiang, Institute of Environmental Medicine, Kar­ olinska Institutet, Stockholm, Sweden, and colleagues determined the presence of antibodies to CarP– fetal calf serum (FCS) and fibrino­ gen (CarP-Fib) in 846 patients with RA from the Leiden Early Arthritis Clinic (EAC), and almost 2000 patients with RA from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA).

“The detection of autoantibodies in sera of RA patients has opened up possibilities of subgrouping the RA population to allow more precise prog­ nosis and possibly therapeutic manage­ ment,” according to the investigators.

Using enzyme-linked immunosor­ bent assays, Dr Jiang and colleagues evaluated the frequency of anti-CarP as it relates to anti–cyclic citrullinat­ ed protein (CCP) immunoglobulin G in patients with RA and found that antibodies to CarP-FCS and CarP-Fib existed in both cohorts.

Anti-CarP antibody positivity was observed in 49% to 73% of patients with anti–CCP-positive RA, and in 8% to 14% of patients with anti– CCP-negative RA—the differences were statistically significant.

24

I

KEY POINTS Autoantibodies are a useful marker in the diagnosis and classification of RA, as well as in the determination of disease severity and development

➤

Detection of autoantibodies in sera of RA patients has opened up possibilities of subgrouping the RA population to allow more precise prognosis and possibly therapeutic management

➤

In stratified analyses, HLA-DRB1*13 alleles showed protective effects against anti–CCP-positive RA, especially in double-positive (CCP+/ CarP+) subgroups

➤

In addition, the researchers fur­ ther analyzed the impact of HLADRB1 alleles on disease risk in

No association was observed between anti-CarP antibodies and smoking, PTPN22 genotype variants, or HLA-DRB1 alleles.

different types of RA and found a significant strong risk effect in anti–CCP-positive RA. This find­ ing was observed regardless of antiCarP antibody status, in both EIRA and EAC cohorts, as well as in the meta-analysis that was observed, the study authors noted.

Taking a closer look at the associ­ ation of different HLA-DRB1 alleles and disease risk in different RA sub­ sets, they found that several alleles, including HLA-DRB1*03 and HLADRB1*07, were associated with pro­ tection against anti–CCP-positive

RHEUMATOLOGY PRACTICE MANAGEMENT

I December 2014

RA, especially in double-positive (CCP+/CarP+) subgroups. These data were collected through unstrat­ ified analyses, however, and after stratification, only HLA-DRB1*13 alleles showed protective effects.

The investigators also evaluated a subset of patients with ACPAnegative RA. No association was observed between anti-CarP anti­ bodies and smoking, PTPN22 genotype variants, or HLA-DRB1 alleles; an association was, however, observed between anti–CarP-FCS antibodies and HLA-DRB1*03.

“These data suggest that antiCarP antibody induction may be facilitated by different mecha­ nisms than the ones involved in the induction of ACPA,” Dr Jiang and colleagues explained. No spe­ cific association between anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes, or smoking was seen after further anal­ ysis was performed.

Overall, data by Dr Jiang and colleagues indicate that different biological mechanisms may be asso­ ciated with the formation of antiCarP versus anti-CCP antibodies in patients with ACPA-positive and ACPA-negative RA. l

Wealth Management

Ten Tips to Cut Your 2014 Taxes

By Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

M

ost people are familiar with the old adage about life’s 2 certainties: taxes, like death, are inevitable. But why pay more in taxes than you have to? This article provides 10 potential tax-saving oppor­ tunities for 2014. The key is to take the time to evaluate which of these concepts, if any, may work in your situ­ ation. There is still time to take advan­ tage of these 10 tax-saving opportuni­ ties before December 31, 2014.

1

If you have not been contributing to your 401(k) and 403(b) plans at the maximum rate all year, increase your contributions. This year, you can put up to $17,500 into your 401(k) or 403(b) plan. Anyone aged ≥50 years by December 31, 2014, can put away an additional $5500 (for a total of $23,000). Contributing to a 401(k) or 403(b) plan at work is one of the best tax shelters available to you during your working years.

2

If you are self-employed, consider setting up a Solo 401(k) by December 31, 2014. A Solo 401(k) plan allows a self-employed person to reach the $52,000 retirement plan maximum with less income than a SEP-IRA. It also allows people aged ≥50 years to put away an additional $5500 (for a total of $57,500) into a retirement plan for 2014.

3

To avoid an underpayment penalty, review your withholdings and instruct your employer to withhold additional taxes if you have not had enough taxes withheld during the year. The IRS Withholding Calculator for 2015 is available at www.irs.gov/Individuals/ IRS-Withholding-Calculator.

4

Consider selling your investments held in nonretirement

accounts that have depreciated.

Since your capital losses can offset other capital gains realized during the year (including those from your mutual funds), excess losses can then be used to offset up to $3000 of wages and other income. However, wait at least 31 days before buying back secu­ rity sold at a loss, or the IRS will not allow the loss under “wash sale” rules.

5

If you are in the lowest tax bracket, consider selling your investments that have increased in value.

Since the capital gains rate will be 0%, those securities can be bought back, and the “cost-basis” will be the higher amount. This strategy will save you taxes when you sell these securities in the future. Ensure that the capital gains realized don’t push you out of the 15% tax bracket, or you will be taxed on gains that fall outside that range.

6

Send in your January 2015 mortgage payment early enough for processing before December 31, 2014. You can deduct the interest portion of that payment a year earli­ er by sending in your payment a few weeks early.

7

Clean out your closets; donate your clothing and household items to a charitable organization, since itemized “noncash” contributions are tax deductible.

Remember to get a receipt. Make an itemized list that includes condi­ tion of the donated items, and take a few pictures of the items as well.

Only donations of clothing and household items in “good condition or better” qualify for a deduction.

8

Making monetary donations by credit card before December 31, 2014, allows you to deduct the donation on this year’s return, even if you

December 2014

I

Andrew D. Schwartz

Lawrence B. Keller

don’t pay your credit card bill until 2015. You always have the option of donating to charities any investments that have appreciated. You can claim your donation based on the value of the donated assets without paying capital gains taxes on the appreciation.

9

Prepay your projected state tax shortfall if you will be itemizing your deductions and you will not be subject to the alternative minimum tax.

10

Prepay and pay off your medical bills if your total medical expenses exceed 10% of your income and you itemize. The threshold in­creased from 7.5% to 10% in 2013, except for people aged >65 years, for whom the threshold remains at 7.5%.

This month, evaluate whether you will save taxes by postpon­ ing 2014 income or deductions into 2015 or by accelerating 2015 income or deductions into 2014. l Andrew D. Schwartz, CPA, is a partner in the Boston CPA firm Schwartz & Schwartz, PC, and is also the founder of the MDTAXES Network (www. mdtaxes.com). He can be reached at 800-471-0045 or by e-mail to Andrew@ mdtaxes.com.

Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF, is the founder of Physician Financial Services. He can be reached at 800-481-6447 or by e-mail to Lkeller@physicianfinancial services.com.

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25

Drug Update

Rasuvo (Methotrexate) Once-Weekly Subcutaneous Injection with Flexible Dosing Approved by the FDA for Rheumatoid Arthritis, Polyarticular Juvenile Idiopathic Arthritis, and Severe Psoriasis

By Loretta Fala, Medical Writer

I

nflammatory autoimmune con­ ditions can affect different body systems, resulting in a variety of diseases involving the joints, skin, brain, and other organs.

Rheumatoid arthritis, gout, juve­ nile idiopathic arthritis, psoriasis, and psoriatic arthritis are among the common chronic inflammatory autoimmune diseases affecting mil­ lions of Americans annually.

Rheumatoid Arthritis Rheumatoid arthritis, a chronic inflammatory, autoimmune disorder that affects the lining (synovium) of the joints, affects 1.3 million people in the United States.1 Aside from causing painful swelling that may eventually lead to bone erosion and joint deformity, rheumatoid arthri­ tis can also affect other organs of the body, including the skin, eyes, lungs, and blood vessels.1,2 Patients with rheumatoid arthri­ tis have a high risk for disability and mortality, and they are twice as likely to die as people of the same age without rheumatoid arthritis.3 Approximately 40% of all deaths associated with rheumatoid arthri­ tis are attributed to cardiovascular causes, including ischemic heart disease and stroke.3 Rheumatoid arthritis has a sub­ stantial impact on a patient’s func­ tional status and quality of life.3 In Copyright © 2014 American Health & Drug Benefits. All rights reserved.

Used with permission.

26

I

addition, this disease is associated with substantial direct and indi­ rect costs. According to one study, rheumatoid arthritis accounted for $19.3 billion (2005 dollars) in societal costs, excluding intangible costs, which rose to $39.2 billion when intangible costs were added.4 The management goals for patients with rheumatoid arthri­ tis include reducing joint pain and swelling, alleviating stiffness, and preventing joint damage.1 According to the 2012 American College of Rheumatology (ACR) recommendations for the use of dis­ ease-modifying antirheumatic drugs (DMARDs) and biologic agents in the treatment of rheumatoid arthri­ tis, “The goal for each rheumatoid arthritis patient should be low dis­ ease activity or remission. In ideal circumstances, rheumatoid arthritis remission should be the target of therapy, but in others, low disease activity may be an acceptable tar­ get.”5 The ACR recommendations also state that decisions about treat­ ing to target are left to the clinician caring for the individual patient, based on the patient’s preferences, comorbid conditions, and other rel­ evant factors. Moreover, treatment plans involve patient-tailored risk– benefit analysis based on the clini­ cian’s assessment and collaboration with the patient.5 The early diagnosis and treatment of rheumatoid arthritis are vital.1 More aggressive treatment in early rheumatoid arthritis may improve

RHEUMATOLOGY PRACTICE MANAGEMENT

I December 2014

outcomes, prevent irreversible joint damage, and preserve physical function and health-related qual­ ity of life.5 Therapies for rheuma­ toid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, DMARDs (ie, methotrex­ ate, leflunomide, hydroxychloro­ quine, and sulfasalazine), immuno­ suppressants, tumor necrosis factor (TNF)-alpha inhibitors, and other biologic anti-inflammatory agents.2

Polyarticular Juvenile Idiopathic Arthritis Rheumatoid arthritis charac­ teristically develops in adults, but it can affect people of all ages.

When rheumatoid arthritis affects young individuals aged <16 years, the condition is called juvenile arthritis. Although juvenile arthri­ tis generally develops in children before age 16 years, symptoms may start as early as 6 months of age.6 Approximately 300,000 children in the United States have been diag­ nosed with some form of juvenile arthritis.7 An estimated 40% of all cases of juvenile arthritis are poly­ articular disease.8 Polyarticular juvenile idiopathic arthritis (pJIA) is characterized by the involvement of many joints (≥5), which may include the large and small joints of the legs and arms, as well as the jaw and neck.

The polyarticular form of juvenile arthritis may eventually evolve into rheumatoid arthritis.

The symptoms of pJIA include

Drug Update

swollen or warm joints, limping, rash, sudden high fever, joint stiffness or pain, and swollen glands.6 Other disease manifestations may include red eyes, eye pain, photophobia, or vision changes. The severity of dis­ ease corresponds with the number of major joints affected.6 Complications of pJIA include erosion or destruction of the joints, a slow rate of growth, vision loss from chronic uveitis, anemia, and pericarditis.6 Moreover, children affected with pJIA may have poor school attendance as a result of chronic pain.6 In addition to its substantial health impact on young patients, juvenile arthritis diseases in the United States account for an estimated $285 million annu­ ally in direct costs, based on 1989 data from the Centers for Disease Control and Prevention.8 The treatment goal for patients with pJIA is to control symptoms, prevent joint damage, and help them maintain function.7 First-line therapy for pJIA includes NSAIDs, which are administered in a dose appropriate for the child’s weight.

If a response is not achieved with NSAIDs, DMARDs are used as sec­ ond-line therapy. These DMARDs include methotrexate and biolog­ ic agents, which consist of several TNF-alpha inhibitors.7

They also have an elevated risk for cardiovascular disease, Parkinson’s disease, kidney disease, and other autoimmune diseases.11 Moreover, psoriasis has a dramatic impact on a patient’s quality of life and selfesteem. It can lead to depression, social isolation, and problems at work.11 Psoriasis also imposes a sub­ stantial financial burden on affected individuals, as well as on the nation­ al healthcare costs. The annual US costs attributable to psoriasis totaled a staggering $11.25 billion in 2008.9 The treatment goals for patients with psoriasis include slowing the speed of skin growth to reduce in­ flammation and plaque formation, removing skin scales, and smooth­ ing the skin.11 Topical treatments include topical corticosteroids, vitamin D analogs, anthralin, top­ ical retinoids, calcineurin inhibi­ tors, salicylic acid, and coal tar.12 Phototherapy (artificial ultraviolet A and ultraviolet B lights) is some­ times used alone or in combina­ tion with other medications. Oral or injectable therapies for psoriasis include methotrexate, retinoids, cyclosporine, and biologic immuno­ modulator agents, including several TNF-alpha inhibitors (ie, etaner­ cept, infliximab, adalimumab) and the interleukin-12/interleukin-23 inhibitor, ustekinumab.12

Psoriasis Psoriasis is a chronic, inflamma­ tory autoimmune skin disease that is often accompanied by thick, itchy, red patches that can be painful.9 In some cases, the disease is disfiguring and disabling. The most prevalent autoimmune disease in the United States, psoriasis affects an estimated 7.5 million people.9 Severe psoriasis is characterized by involvement of more than 10% of the body.10 Individuals with psoriasis have an increased risk for developing psori­ atic arthritis, eye disorders, obesity, type 2 diabetes, and hypertension.11

Methotrexate Injection Approved in 10 Dosage Strengths for 3 Autoimmune Conditions Oral methotrexate has been avail­ able for the treatment of inflam­ matory autoimmune disorders for many years. In fact, for more than 2 decades, methotrexate has been recognized as a cornerstone therapy for patients with rheuma­ toid arthritis and severe psoriasis.

The first once-weekly subcutane­ ous formulation of methotrexate (Otrexup; Antares Pharma) was approved by the US Food and Drug

December 2014

I

Administration (FDA) in 2013 for adults with severe active rheuma­ toid arthritis who do not respond to or cannot tolerate first-line ther­ apy, for children with active pJIA, and for adults with severe, refractory psoriasis.13 In July 2014, the FDA approved a new once-weekly subcutaneous injection of methotrexate (Rasuvo; Medac Pharma) for the treatment of patients with rheumatoid arthritis, pJIA, or psoriasis.14 The new meth­ otrexate injection is administered once weekly subcutaneously via an autoinjector pen. Methotrexate injection is not indicated for the treatment of neoplastic diseases.15 Eric Ruderman, MD, Professor of Medicine, Northwestern University Feinberg School of Medicine, said in a press release from Medac Pharma, “As a rheumatologist, I believe Rasuvo will offer patients the opportunity to maximize the benefit they get from methotrexate.

Rasuvo’s dosing flexibility, in par­ ticular, will be very helpful, as RA patients do not all respond equally to methotrexate, making it impor­ tant to select a treatment regimen that is appropriate for the patient’s condition.”14 The subcutaneous delivery of methotrexate injection and its avail­ ability in 10 dosage strengths (ranging from 7.5 mg to 30 mg) was designed to improve its bioavailability, accord­ ing to the manufacturer.14 Results of a clinical study showed that subcutane­ ous methotrexate administration with a prefilled autoinjector pen led to a higher relative bioavailability com­ pared with oral administration of the drug.16 The use of oral methotrexate is associated with gastrointestinal side effects, including nausea and abdom­ inal pain.17 Studies suggest that the subcutaneous pen administration of methotrexate is associated with fewer, less intense gastrointestinal adverse events than oral methotrexate.16,17 Continued on page 28

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27

Drug Update

Rasuvo (Methotrexate) Once-Weekly…Continued from page 27 Mechanism of Action Methotrexate works by inhibit­ ing dihydrofolic acid reductase.15 Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be used as carriers of one-carbon groups in synthesizing purine nucleotides and thymidylate.

Methotrexate interferes with the synthesis and repair of DNA, as well as cellular replication. In gener­ al, actively proliferating tissues (eg, malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder) are more sensitive to this effect of methotrexate.15 The mechanism of action of methotrexate in patients with rheu­ matoid arthritis is unknown, but it may affect immune function.

The production rate of epithelial cells in the skin is greatly increased in patients with psoriasis versus patients with normal skin. This dif­ ferential in proliferation rates serves as the basis for using methotrexate to control the process of psoriasis.15 Dosing and Administration Methotrexate injection is adminis­ tered once weekly subcutaneously in the abdomen or the thigh. A different formulation of methotrexate should be used instead of the subcutaneous form for patients requiring oral, intra­ muscular, intravenous, intra-arterial, or intrathecal dosing; doses of <7.5 mg weekly; doses >30 mg weekly; high-dose regimens; or dose adjust­ ments of <2.5-mg increments.

The starting doses of methotrex­ ate are listed in the Table. The dose should be adjusted gradually in the individual patient to achieve an optimal response.

Methotrexate injection is avail­ able as a single dose from a manu­ ally triggered autoinjector pen that delivers the drug. It is available in

28

I

Table. Starting Doses for the Subcutaneous Injection of Methotrexate Indication

Starting dosea

Rheumatoid arthritis

7.5 mg once weeklyb

Polyarticular juvenile idiopathic arthritis

10 mg/m2 once weekly

Psoriasis

10-25 mg once weeklyc

The dose should be adjusted gradually to achieve an optimal response.

Oral formulation is a potential alternative. c Oral, intramuscular, or intravenous formulation is a potential alternative.

Source: Rasuvo (methotrexate) injection prescribing information; July 2014. a

b

10 different dosage strengths, rang­ ing from 7.5 mg to 30 mg, including 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg, and 30 mg.14,15

Clinical Studies In patients with rheumatoid arthritis, clinical trials were per­ formed using other formulations of methotrexate. The effects of meth­ otrexate on articular swelling and tenderness can be seen as early as 3 to 6 weeks after the start of treat­ ment in patients with rheumatoid arthritis. Most studies of metho­ trexate in patients with rheuma­ toid arthritis have been of relatively short duration (3-6 months). Based on limited data from long-term stud­ ies, an initial clinical improvement should be maintained for at least 2 years with continuous therapy with subcutaneous methotrexate.15 Clinical trials in patients with pJIA were performed using for­ mulations other than subcutane­ ous methotrexate.15 Treatment with methotrexate was evaluated in a 6-month, double-blind, placebocontrolled study in 127 pediatric patients with pJIA (mean age, 10.1 years; mean duration of disease, 5.1 years).15,18 This study showed that in patients receiving background NSAIDs and/or prednisone, metho­

RHEUMATOLOGY PRACTICE MANAGEMENT

I December 2014

trexate given weekly at an oral dose of 10 mg/m2 resulted in significant clinical improvement compared with placebo as measured by the physician’s global assessment or by a patient composite (ie, 25% reduc­ tion in the articular severity score plus improvement based on parent and physician global assessments of disease activity).15,18 More than 66% of the patients in this study had pJIA; the numerically greatest response was seen in this subgroup of patients who received 10 mg/m2 per week of methotrex­ ate.15,18 The overwhelming major­ ity of the remaining patients had systemic-course juvenile idiopathic arthritis. All patients were unre­ sponsive to NSAIDs; approximately 33% were receiving low-dose cor­ ticosteroids.15,18 The 5-mg/m2 dose of weekly methotrexate was not significantly more effective than placebo.15,18

Safety The most common adverse reac­ tions associated with methotrex­ ate injection are nausea, abdominal pain, dyspepsia, stomatitis/mouth sores, rash, nasopharyngitis, diar­ rhea, liver function test abnormal­ ities, vomiting, headache, bronchi­ tis, thrombocytopenia, alopecia, leukopenia, pancytopenia, dizziness,

Drug Update

photosensitivity, and burning of skin lesions.15

Contraindications Methotrexate injection is con­ traindicated in pregnant women, nursing mothers, and in patients affected by alcoholism or those with liver disease, immunodeficien­ cy syndromes, preexisting blood dyscrasias, or hypersensitivity to methotrexate.15 Drug Interactions Aspirin, NSAIDs, and steroids.

The concomitant use of methotrex­ ate injection with aspirin, NSAIDs, and steroids may elevate and pro­ long serum methotrexate levels and may cause increased toxicity.15 Proton pump inhibitors. The concomitant use of methotrexate injection with proton pump inhibi­ tors may prolong serum methotrex­ ate levels and may cause increased toxicity.15 Hepatotoxins. Patients receiving concomitant treatment with meth­ otrexate and potential hepatotox­ ins (eg, azathioprine, retinoids, and sulfasalazine) should be monitored closely for the possible increased risk for hepatotoxicity.15 Theophylline. Methotrexate may decrease the clearance of theophyl­ line; theophylline levels should be monitored when taken concurrent­ ly with methotrexate.15 Folic acid and antifolates.

Vitamin preparations containing folic acid or its derivatives may decrease the response to systemical­ ly administered methotrexate.15 Mercaptopurine. Methotrexate increases the plasma levels of mercap­ topurine. The combination of meth­ otrexate and mercaptopurine may therefore require dose adjustment.15 Other drugs. Methotrexate is par­ tially bound to serum albumin, and its toxicity may be increased because of displacement by certain drugs, such as salicylates, phenylbutazone,

phenytoin, and sulfonamides. The use of methotrexate with probene­ cid should be monitored carefully, because renal tubular transport is also diminished by probenecid.15

Warnings and Precautions Boxed warnings. The prescrib­ ing information for methotrexate injection carries a boxed warning stating that serious toxic reactions and death have been reported with its use, and that patients should be monitored closely for bone marrow, liver, lung, skin, and kidney toxici­ ties. Methotrexate has been reported to cause fetal death and/or congeni­ tal anomalies and is contraindicated in pregnancy. Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant admin­ istration of methotrexate (usually in high dosage) with some NSAIDs.15 The boxed warning also notes the risk for hepatotoxicity, fibro­ sis, and cirrhosis, which may occur after prolonged use of methotrexate.

Methotrexate may cause interstitial pneumonitis at any time during therapy; this has been reported at low doses. Consequently, pulmo­ nary symptoms—especially a dry, nonproductive cough—may require interruption of treatment and care­ ful investigation.15 In addition, diarrhea, ulcerative stomatitis, hemorrhagic enteritis, and death from intestinal perfora­ tion may occur, as well as poten­ tially fatal opportunistic infections.

Severe, occasionally fatal, skin reac­ tions have also been reported.15 Organ system toxicity. Serious toxic reactions are possible with this medication. Methotrexate should only be used by physicians who are experienced in antimetabolite therapy.15 Embryofetal toxicity. Methotrexate is not recommended for women of childbearing potential unless medical

December 2014

I

evidence shows that the benefits will outweigh the risks. Women of child­ bearing potential should not start taking methotrexate until pregnancy is excluded and should be counseled about the serious risk to the fetus if they become pregnant while under­ going treatment. Pregnancy should be avoided if the man or the woman is receiving methotrexate (a minimum of 3 months for men, and for at least 1 ovulatory cycle after therapy for women).15 Effects on reproduction. Metho­ trexate may cause infertility, oli­ gospermia, and menstrual dys­ function; these effects should be discussed with all patients.15 Laboratory tests. Patients using subcutaneous methotrexate injec­ tion should be monitored closely to detect any toxic effects prompt­ ly. Complete blood counts, renal function, and liver function tests should be performed at the intervals recommended in the prescribing information.15 Risks from improper dosing.

The physician and the pharmacist should emphasize to the patient that subcutaneous methotrexate is administered once weekly and that mistaken daily use has led to fatal toxicity.15 Patients with impaired renal function, ascites, or pleural effusions. Because methotrexate elim­ ination is reduced in patients with impaired renal function, ascites, or pleural effusions, such patients require especially careful monitor­ ing for toxicity as well as dose reduction or, in some cases, the discontinuation of methotrexate.15 Dizziness and fatigue. Adverse reactions from methotrexate, such as dizziness and fatigue, may affect the ability to drive or operate machinery.15 Malignant lymphomas. NonHodgkin’s lymphoma and other tumors have been reported in Continued on page 30

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29

Drug Update

Rasuvo (Methotrexate) Once-Weekly…Continued from page 29 patients receiving low-dose oral methotrexate; however, some cases of malignant lymphoma related to low-dose oral methotrexate have regressed completely after the with­ drawal of methotrexate, without requiring active antilymphoma treatment. Methotrexate should be discontinued, and if the lymphoma does not regress, appropriate treat­ ment should be instituted.15 Tumor lysis syndrome. Like other cytotoxic drugs, methotrexate may induce tumor lysis syndrome in patients with rapidly growing tumors.15 Concomitant radiation therapy.

Methotrexate given concomitant­ ly with radiotherapy may increase the risk for soft-tissue necrosis and osteonecrosis.15

Use in Specific Populations Pediatric use. The safety and efficacy of methotrexate injection have not been established in pediat­ ric patients with psoriasis or in pedi­ atric patients with malignancy.15 Geriatric use. Clinical studies of methotrexate did not include sufficient numbers of patients aged ≥65 years to determine wheth­ er they respond to it differently from younger patients. In gener­ al, dose selection for an elderly patient should be done cautiously, reflecting the greater frequency of decreased hepatic and renal func­ tions, decreased folate stores, and concomitant disease or other drug

therapy (ie, that interfere with renal function, methotrexate, or folate metabolism) in this population.15

Conclusion The recent FDA approval of methotrexate subcutaneous injec­ tion marks the availability of a new once-weekly therapeutic option for patients with severe rheumatoid arthritis or pJIA who do not tolerate or respond to first-line treatment, and for patients with severe psoriasis who do not respond to other treat­ ments.14 Methotrexate subcutaneous injection is available in 10 dosage strengths, providing a wide range of patient-tailored dosing options.

In clinical studies, the subcutaneous delivery of once-weekly methotrex­ ate via an autoinjector pen resulted in a higher relative bioavailability than oral methotrexate; furthermore, it is associated with fewer, less severe gastrointestinal adverse events than oral methotrexate.16,17 l References

1. Ruderman E, Tambar S; for the American College of Rheumatology. Rheumatoid arthritis. Updated August 2012. www.rheumatology.org/practice/clini cal/patients/diseases_and_conditions/ra.asp. Accessed November 10, 2014.

2. Mayo Clinic. Rheumatoid arthritis. October 29, 2014. www.mayoclinic.org/diseases-conditions/rheu matoid-arthritis/basics/definition/con-20014868.

Accessed November 10, 2014.

3. Centers for Disease Control and Prevention.

Rheumatoid arthritis. Updated November 6, 2014. www.cdc.gov/arthritis/basics/rheumatoid.htm.

Accessed November 10, 2014.

4. Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010;26:77-90.

5. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recom­

mendations for the use of disease-modifying antirheu­ matic drugs and biologic agents in the treatment of rheu­ matoid arthritis. Arthritis Care Res. 2012;64:625-639.

6. MedlinePlus. Juvenile rheumatoid arthritis. Updated April 20, 2013. www.nlm.nih.gov/medlineplus/ency/ article/000451.htm. Accessed October 15, 2014.

7. Abramson LS; for the American College of Rheu­ matology. Arthritis in children. Updated May 2013. www. rheumatology.org/practice/clinical/patients/diseases_and_ conditions/juvenilearthritis.asp. Accessed October 15, 2014.

8. Centers for Disease Control and Prevention. Child­ hood arthritis. Updated October 23, 2013. www.cdc. gov/arthritis/basics/childhood.htm. Accessed October 15, 2014.

9. National Psoriasis Foundation. Psoriasis and comor­ bid conditions issue brief. Executive summary. January 2012. www.psoriasis.org/document.doc?id=793.

Accessed October 17, 2014.

10. National Psoriasis Foundation. Psoriasis severity. www.psoriasis.org/about-psoriasis/treatments/severity.

Accessed October 17, 2014.

11. Mayo Clinic staff. Psoriasis. April 11, 2014. www. mayoclinic.org/diseases-conditions/psoriasis/basics/symp toms/con-20030838?p=1. Accessed October 17, 2014.

12. National Psoriasis Foundation. Moderate to severe psoriasis: biologic drugs. www.psoriasis.org/about-psori asis/treatments/biologics. Accessed October 17, 2014.

13. Brooks M. FDA OKs methotrexate autoinjec­ tor (Otrexup). October 18, 2013. Medscape. www. medscape.com/viewarticle/812821. Accessed October 22, 2014.

14. Medac Pharma, Inc. Medac Pharma, Inc. secures FDA approval of Rasuvo (methotrexate) injection for rheumatoid arthritis, poly-articular-course juvenile idiopathic arthritis and psoriasis. Press release. July 14, 2014. www.medacpharma.com/u-s-district-court-forthe-district-of-delaware-concurrently-denies-motionfor-preliminary-injunction-filed-by-antares-pharmainc/. Accessed November 10, 2014.

15. Rasuvo (methotrexate) injection [prescribing infor­ mation]. Chicago, IL: Medac Pharma, Inc; July 2014.

16. Pichlmeier U, Heuer KU. Subcutaneous admin­ istration of methotrexate with a prefilled autoinjector pen results in a higher relative bioavailability com­ pared with oral administration of methotrexate. Clin Exp Rheumatol. 2014;32:563-571.

17. Rutkowska-Sak L, Rell-Bakalarska M, Lisowska B. Oral vs. subcutaneous low-dose methotrexate treatment in reducing gastrointestinal side effects.

Reumatologia. 2009;47:207-211.

18. Giannini EH, Brewer EJ, Kuzmina N, et al; for the Pediatric Rheumatology Collaborative Study Group, and the Cooperative Children’s Study Group.

Methotrexate in resistant juvenile rheumatoid arthritis: results of the U.S.A.–U.S.S.R. double-blind, placebocontrolled trial. N Engl J Med. 1992;326:1043-1049.

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