2020 March AANnews

VOLUME 33 · ISSUE 3 · March 2020

GET TOP EDUCATION, SCIENCE, NETWORKING—AT A DISCOUNT Register Before April 2 There’s still time to receive the Advance Registration discounted rate for the 2020 Annual Meeting coming to beautiful and diverse Toronto this April 25 through May 1. Visit AAN.com/view/AM20 before April 2 to take advantage of the savings, and then start preparing for neurology’s preeminent, can’t-miss meeting featuring more than 500 expert-led courses and experiential learning areas covering the full spectrum of neurology; the highest-quality, innovative discoveries and science like no other; and unparalleled networking opportunities within your community of neurology professionals from over 100 countries around the globe. 

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Science, Knowledge, and Recognition Intersect at Research Experiential Learning Area

SPORTS CONCUSSION

Cutting-edge science, knowledge sharing, and career recognition will come together through lively presentations, scientific sessions, award and scholarship recipient recognition, networking, and more at this year’s Research Experiential Learning Area during the Annual Meeting in Toronto.

JULY 17–19, 2020 MINNEAPOLIS, MN

CONFERENCE

The always popular AAN Sports Concussion Conference will make its debut in Minneapolis this July 17 through 19. With a major international airport that provides easy access, the Twin Cities are a vibrant destination brimming with arts, Continued on page 17

12 Stronger Business Administrators Make a Stronger Practice

Continued on page 15

›

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21 Report MIPS Data by End of March

33 Impressive Lineup of Honorees Slated for Commitment to Cures Fundraiser

In patients with relapsing forms of multiple sclerosis (RMS)

START WITH THE POWER AND EXPERIENCE OF TYSABRI

IN THE FIGHT AGAINST RMS In the 2-year AFFIRM pivotal trial:

83%

of patients taking TYSABRI had no sustained physical disability progression for 12 weeks vs 71% with placebo (primary endpoint: percentage with sustained increase in disability was 17% vs 29%; p<0.001)1,2

INDICATION TYSABRI® (natalizumab) is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk.

IMPORTANT SAFETY INFORMATION WARNING: Progressive Multifocal Leukoencephalopathy (PML) TYSABRI® (natalizumab) increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH® Prescribing Program.

Infection by the JC Virus (JCV) is required for the development of PML There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs Postmarketing data suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value) MRI findings may be apparent before clinical signs or symptoms suggestive of PML. Monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present.

Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following TYSABRI discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis Important Safety Information continues on the following pages. Please see accompanying brief summary of full Prescribing Information, including Boxed Warning.

T RUS T IN 10 + Y E A R S O F E XPER IEN CE WI T H T Y S A B R I OVER

ALWAYS

APPROXIMATELY

200,000

COMMITTED TO SAFETY

NEW PATIENTS

globally for relapsing MS with the established therapy of TYSABRI, and counting3,a

The TOUCH® Prescribing Program helps you support patients throughout their treatment on TYSABRI

in the US who start TYSABRI have received no previous DMT4,b

PATIENTS TREATED

1 IN 4

DMT=disease-modifying therapy; a202,300 patients as of August 20193; b24.3% of patients as of data on file from November 2018. 4

VISIT TimeForTYSABRI.com IMPORTANT SAFETY INFORMATION WARNING: Progressive Multifocal Leukoencephalopathy (PML) (cont’d) PML has been reported after discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least 6 months after discontinuation of TYSABRI Adverse events that may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI-treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation JCV infection of granule cell neurons in the cerebellum, i.e., JCV granule cell neuronopathy (GCN), with symptoms similar to PML, has been reported in patients treated with TYSABRI. JCV GCN can occur with or without concomitant PML and can cause cerebellar dysfunction. Diagnosis and management of JCV GCN should follow guidance provided for PML Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI-treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It presents as a clinical decline in the patient’s condition after TYSABRI removal (and, in some cases, after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In TYSABRI-treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange.

Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken Contraindications TYSABRI is contraindicated in patients who have or have had PML TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI TYSABRI TOUCH Prescribing Program Because of the risk of PML, TYSABRI is available only through a restricted distribution program under a REMS called the TOUCH® Prescribing Program Patients must be enrolled in the TOUCH Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI, and complete and sign the Patient-Prescriber Enrollment Form Herpes Infections – Encephalitis, Meningitis and Acute Retinal Necrosis TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI The duration of treatment with TYSABRI prior to onset ranged from a few months to several years Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered Important Safety Information continues on the following pages. Please see accompanying brief summary of full Prescribing Information, including Boxed Warning.

IMPORTANT SAFETY INFORMATION (cont’d) Herpes Infections – Encephalitis, Meningitis and Acute Retinal Necrosis (cont’d) Patients being administered TYSABRI are at a higher risk of acute retinal necrosis (ARN), a fulminant viral infection of the retina caused by the family of herpes viruses. Patients with eye symptoms such as decreased visual acuity, redness or eye pain should be referred for retinal screening as serious cases of ARN can lead to blindness of one or both eyes Following clinical diagnosis of ARN, consider discontinuation of TYSABRI Hepatotoxicity Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence) Hypersensitivity/Antibody Formation Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1% Reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain If a hypersensitivity reaction occurs, discontinue administration of TYSABRI and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared with patients who did not develop antibodies to TYSABRI in both MS and CD studies Patients who receive TYSABRI for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment Immunosuppression/Infections The immune system effects of TYSABRI may increase the risk for infections In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in TYSABRI-treated patients than in placebotreated patients. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1 In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids In a long-term safety study of patients, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of TYSABRI-treated patients Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections over the risk observed with use of TYSABRI alone In Studies MS1 and MS2, the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebo-treated patients In Study MS1, the incidence of serious infections was approximately 3% in TYSABRI-treated patients and in placebo-treated patients.

Most patients did not interrupt treatment with TYSABRI during infections Laboratory Test Abnormalities In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient Adverse Reactions The most common adverse reactions reported at an incidence of ≥10% with TYSABRI and ≥2% difference with placebo were headache (38% vs 33%), fatigue (27% vs 21%), infusion reactions (24% vs 18%), urinary tract infections (21% vs 17%), arthralgia (19% vs 14%), depression (19% vs 16%), pain in extremity (16% vs 14%), rash (12% vs 9%), gastroenteritis (11% vs 9%), and vaginitis (10% vs 6%) The most frequently reported serious adverse reactions in Study MS1 were infections (3.2% vs 2.6% placebo), including urinary tract infection (0.8% vs 0.3%) and pneumonia (0.6% vs 0%), acute hypersensitivity reactions (1.1% vs 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% vs 0%]), depression (1.0% vs 1.0%, including suicidal ideation or attempt [0.6% vs 0.3%]), and cholelithiasis (1.0% vs 0.3%) Based on animal data, TYSABRI may cause fetal harm. TYSABRI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Please see accompanying brief summary of full Prescribing Information, including Boxed Warning.

STUDY DESCRIPTION: The AFFIRM (NAtalizumab Safety and EFFIcacy in Relapsing-Remitting MS) study was a pivotal 2-year, double-blind, randomized, controlled trial with 942 relapsing MS patients who received either TYSABRI therapy (300 mg by intravenous infusion [n=627]) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions).1,2 References: 1. TYSABRI Prescribing Information, Cambridge, MA: Biogen 2. Polman CH, O’Connor PW, Havrdova E, et al; for the AFFIRM investigators.

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899-910. 3. Data on file as of September 2019, Biogen.

4. Data on file as of November 2018, Biogen. © 2019 Biogen. All rights reserved. 12/19 TYS-US-2311 v2

TYSABRI (natalizumab) injection, for intravenous use Brief Summary of Full Prescribing Information WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability.

Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [see Warnings and Precautions (5.1)].

• Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [see Contraindications (4), Warnings and Precautions (5.1)].

• Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH® Prescribing Program [see Warnings and Precautions (5.2)].

1.

INDICATIONS AND USAGE 1.1. Multiple Sclerosis (MS) TYSABRI is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. TYSABRI increases the risk of PML [see Warnings and Precautions (5.1)]. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk.

2.

DOSAGE AND ADMINISTRATION 2.1. Multiple Sclerosis (MS) Only prescribers registered in the MS TOUCH® Prescribing Program may prescribe TYSABRI for multiple sclerosis [see Warnings and Precautions (5.2)].The recommended dose of TYSABRI for multiple sclerosis is 300 mg intravenous infusion over one hour every four weeks.

2.3. Dilution Instructions 1. Use aseptic technique when preparing TYSABRI solution for intravenous infusion. Each vial is intended for single use only. Discard any unused portion.

2. TYSABRI is a colorless, clear to slightly opalescent solution. Inspect the TYSABRI vial for particulate material and discoloration prior to dilution and administration. If visible particulates are observed and/or the liquid in the vial is discolored, the vial must not be used.

3. To prepare the diluted solution, withdraw 15 mL of TYSABRI from the vial using a sterile needle and syringe. Inject TYSABRI into 100 mL of 0.9% Sodium Chloride Injection, USP. No other intravenous diluents may be used to prepare the TYSABRI diluted solution.

4. Gently invert the TYSABRI diluted solution to mix completely. Do not shake. Inspect the solution visually for particulate material prior to administration.

5. The final dosage diluted solution has a concentration of 2.6 mg/mL. 6. Following dilution, infuse TYSABRI solution immediately, or refrigerate the diluted solution at 2°C to 8°C, and use within 8 hours. If stored at 2°C to 8°C, allow the diluted solution to warm to room temperature prior to infusion. DO NOT FREEZE. 2.4. Administration Instructions • Infuse TYSABRI 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute). Do not administer TYSABRI as an intravenous push or bolus injection. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP. • Observe patients during the infusion and for one hour after the infusion is complete. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.5)].

• Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with TYSABRI. 3.

DOSAGE FORMS AND STRENGTHS Injection: 300 mg/15 mL (20 mg/mL) colorless and clear to slightly opalescent solution in a single-dose vial for dilution prior to infusion.

4.

CONTRAINDICATIONS • TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [see Warnings and Precautions (5.1)].

• TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI. Observed reactions range from urticaria to anaphylaxis [see Warnings and Precautions (5.5)].

5.

WARNINGS AND PRECAUTIONS 5.1. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability, has occurred in patients who have received TYSABRI. Three factors that are known to increase the risk of PML in TYSABRI-treated patients have been identified: • Longer treatment duration, especially beyond 2 years. There is limited experience in patients who have received more than 6 years of TYSABRI treatment.

• Prior treatment with an immunosuppressant (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil).

• The presence of anti-JCV antibodies. Patients who are anti-JCV antibody positive have a higher risk for developing PML. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI.

Table 1:

Estimated United States Incidence of PML Stratified by Risk Factor

Anti-JCV Antibody Negative

TYSABRI Exposure

<1/1,000

1-24 months 25-48 months 49-72 months

†

Anti-JCV Antibody Positive No Prior Prior Immunosuppressant Immunosuppressant Use Use <1/1,000 1/1,000 3/1,000 12/1,000 6/1,000 13/1,000

Notes: The risk estimates are based on postmarketing data in the United States from approximately 69,000 TYSABRI exposed patients. † Data beyond 6 years of treatment are limited.

The anti-JCV antibody status was determined using an anti-JCV antibody test (ELISA) that has been analytically and clinically validated and is configured with detection and inhibition steps to confirm the presence of JCV-specific antibodies with an analytical false negative rate of 3%.

Retrospective analyses of postmarketing data from various sources, including observational studies and spontaneous reports obtained worldwide, suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value).

Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with TYSABRI. Infection by the JC virus is required for the development of PML. Anti-JCV antibody testing should not be used to diagnose PML. Anti-JCV antibody negative status indicates that antibodies to the JC virus have not been detected. Patients who are anti-JCV antibody negative have a lower risk of PML than those who are positive. Patients who are anti-JCV antibody negative are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result. The reported rate of seroconversion in patients with MS (changing from anti-JCV antibody negative to positive and remaining positive in subsequent testing) is 3 to 8 percent annually. In addition, some patients’ serostatus may change intermittently.

Therefore, patients with a negative anti-JCV antibody test result should be retested periodically. For purposes of risk assessment, a patient with a positive anti-JCV antibody test at any time is considered anti-JCV antibody positive regardless of the results of any prior or subsequent anti-JCV antibody testing. When assessed, anti-JCV antibody status should be determined using an analytically and clinically validated immunoassay. After plasma exchange, wait at least two weeks to test for anti-JCV antibodies to avoid false negative test results caused by the removal of serum antibodies. After infusion of intravenous immunoglobulin (IVIg), wait at least 6 months (5 halflives) for the IVIg to clear in order to avoid false positive anti-JCV antibody test results.

Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom suggestive of PML. Symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months. Withhold TYSABRI dosing immediately and perform an appropriate diagnostic evaluation at the first sign or symptom suggestive of PML. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following TYSABRI discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of TYSABRI or due to differences in disease in these patients.

There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs. PML has been reported following discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least six months following discontinuation of TYSABRI. Because of the risk of PML, TYSABRI is available only under a restricted distribution program, the TOUCH® Prescribing Program.

In multiple sclerosis patients, an MRI scan should be obtained prior to initiating therapy with TYSABRI. This MRI may be helpful in differentiating subsequent multiple sclerosis symptoms from PML. For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. If the initial evaluations for PML are negative but clinical suspicion for PML remains, continue to withhold TYSABRI dosing, and repeat the evaluations.

There are no known interventions that can adequately treat PML if it occurs. Three sessions of plasma exchange over 5 to 8 days were shown to accelerate TYSABRI clearance in a study of 12 patients with MS who did not have PML, although in the majority of patients, alpha-4 integrin receptor binding remained high. Adverse events which may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation.

JC virus infection of granule cell neurons in the cerebellum (i.e., JC virus granule cell neuronopathy [JCV GCN]) has been reported in patients treated with TYSABRI. JCV GCN can occur with or without concomitant PML. JCV GCN can cause cerebellar dysfunction (e.g., ataxia, incoordination, apraxia, visual disorders), and neuroimaging can show cerebellar atrophy. For diagnosis of JCV GCN, an evaluation that includes a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA, is recommended. JCV GCN should be managed similarly to PML. Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It

presents as a clinical decline in the patient’s condition after TYSABRI removal (and in some cases after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In TYSABRI treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.

5.2. TYSABRI TOUCH® Prescribing Program TYSABRI is available only through a restricted program under a REMS called the TOUCH® Prescribing Program because of the risk of PML [see Warnings and Precautions (5.1)].

For prescribers and patients, the TOUCH® Prescribing Program has two components: MS TOUCH® (for patients with multiple sclerosis) and CD TOUCH® (for patients with Crohn’s disease).

Selected requirements of the TOUCH® Prescribing Program include the following: • Prescribers must be certified and comply with the following: – Review the TOUCH® Prescribing Program prescriber educational materials, including the full prescribing information.

– Educate patients on the benefits and risks of treatment with TYSABRI, ensure that patients receive the Medication Guide, and encourage them to ask questions.

– Review, complete, and sign the Patient-Prescriber Enrollment Form.

– Evaluate patients three months after the first infusion, six months after the first infusion, every six months thereafter, and for at least six months after discontinuing TYSABRI. – Determine every six months whether patients should continue on treatment and, if so, authorize treatment for another six months.

– Submit to Biogen the “TYSABRI Patient Status Report and Reauthorization Questionnaire” six months after initiating treatment and every six months thereafter.

– Complete an “Initial Discontinuation Questionnaire” when TYSABRI is discontinued, and a “6-Month Discontinuation Questionnaire” following discontinuation of TYSABRI. – Report cases of PML, hospitalizations due to opportunistic infections, and deaths to Biogen at 1-800-456-2255 as soon as possible.

• Patients must be enrolled in the TOUCH® Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI, and complete and sign the Patient-Prescriber Enrollment Form.

• Pharmacies and infusion centers must be specially certified to dispense or infuse TYSABRI. 5.3. Herpes Infections Herpes Encephalitis and Meningitis TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses. Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI. Laboratory confirmation in those cases was based on positive PCR for viral DNA in the cerebrospinal fluid. The duration of treatment with TYSABRI prior to onset ranged from a few months to several years.

Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered.

Acute Retinal Necrosis Acute retinal necrosis (ARN) is a fulminant viral infection of the retina caused by the family of herpes viruses (e.g., varicella zoster, herpes simplex virus). A higher risk of ARN has been observed in patients being administered TYSABRI. Patients presenting with eye symptoms, including decreased visual acuity, redness, or eye pain, should be referred for retinal screening for ARN. Some ARN cases occurred in patients with central nervous system (CNS) herpes infections (e.g., herpes meningitis or encephalitis). Serious cases of ARN led to blindness of one or both eyes in some patients. Following clinical diagnosis of ARN, consider discontinuation of TYSABRI. The treatment reported in ARN cases included anti-viral therapy and, in some cases, surgery.

5.4. Hepatotoxicity Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses. In some patients, liver injury recurred upon rechallenge, providing evidence that TYSABRI caused the injury. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients.

TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence).

5.5. Hypersensitivity/Antibody Formation Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis), which occurred at an incidence of <1%. These reactions usually occur within two hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. Generally, these reactions are associated with antibodies to TYSABRI. If a hypersensitivity reaction occurs, discontinue administration of TYSABRI, and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI. Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared to patients who did not develop antibodies to TYSABRI in both MS and CD studies. Therefore, the possibility of antibodies to TYSABRI should be considered in patients who have hypersensitivity reactions [see Adverse Reactions (6.2)].

Antibody testing: If the presence of persistent antibodies is suspected, antibody testing should be performed. Antibodies may be detected and confirmed with sequential serum antibody tests. Antibodies detected early in the treatment course (e.g., within the first six months) may be transient and may disappear with continued dosing. It is recommended that testing be repeated three months after an initial positive result to confirm that antibodies are persistent. Prescribers should consider the overall benefits and risks of TYSABRI in a patient with persistent antibodies.

Patients who receive TYSABRI for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment. Given that patients with persistent antibodies to TYSABRI experience reduced efficacy, and that hypersensitivity reactions are more common in such patients, consideration should be given to testing for the presence of antibodies in patients who wish to recommence therapy following a dose interruption. Following a period of dose interruption, patients testing negative for

antibodies prior to re-dosing have a risk of antibody development with re-treatment that is similar to TYSABRI naïve patients [see Adverse Reactions (6.2)].

5.6. Immunosuppression/Infections The immune system effects of TYSABRI may increase the risk for infections. In Study MS1 [see Clinical Studies (14.1)], certain types of infections, including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections, occurred more often in TYSABRI-treated patients than in placebo-treated patients [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1.

In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids.

In a long-term safety study of patients treated with TYSABRI for multiple sclerosis, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of TYSABRI-treated patients.

In CD clinical studies, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of TYSABRI-treated patients; some of these patients were receiving concurrent immunosuppressants [see Warnings and Precautions (5.1), Adverse Reactions (6.1)].

In Studies CD1 and CD2, an increase in infections was seen in patients concurrently receiving corticosteroids. However, the increase in infections was similar in placebo-treated and TYSABRItreated patients who received steroids.

Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections, including PML and other opportunistic infections, over the risk observed with use of TYSABRI alone [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. The safety and efficacy of TYSABRI in combination with antineoplastic, immunosuppressant, or immunomodulating agents have not been established. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not ordinarily be treated with TYSABRI. The risk of PML is also increased in patients who have been treated with an immunosuppressant prior to receiving TYSABRI [see Warnings and Precautions (5.1)].

5.7. Laboratory Test Abnormalities In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient.

5.8. Immunizations No data are available on the effects of vaccination in patients receiving TYSABRI. No data are available on the secondary transmission of infection by live vaccines in patients receiving TYSABRI. 6.

ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Progressive Multifocal Leukoencephalopathy (PML) [see Warnings and Precautions (5.1)] • Herpes Infections [see Warnings and Precautions (5.3)] • Hepatotoxicity [see Warnings and Precautions (5.4)] • Hypersensitivity/Antibody Formation [see Warnings and Precautions (5.5)] • Immunosuppression/Infections [see Warnings and Precautions (5.6)] 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions (incidence ≥ 10%) were headache and fatigue in both the multiple sclerosis (MS) and Crohn’s disease (CD) studies. Other common adverse reactions (incidence ≥ 10%) in the MS population were arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea NOS, and rash. Other common adverse reactions (incidence ≥ 10%) in the CD population were upper respiratory tract infections and nausea.

The most frequently reported adverse reactions resulting in clinical intervention (i.e., discontinuation of TYSABRI) in the MS studies were urticaria (1%) and other hypersensitivity reactions (1%), and in the CD studies (Studies CD1 and CD2) were the exacerbation of Crohn’s disease (4.2%) and acute hypersensitivity reactions (1.5%) [see Warnings and Precautions (5.5)].

A total of 1617 multiple sclerosis patients in controlled studies received TYSABRI, with a median duration of exposure of 28 months. A total of 1563 patients received TYSABRI in all CD studies for a median exposure of 5 months; of these patients, 33% (n=518) received at least one year of treatment and 19% (n=297) received at least two years of treatment.

Multiple Sclerosis Clinical Studies The most common serious adverse reactions in Study MS1 [see Clinical Studies (14.1)] with TYSABRI were infections (3.2% versus 2.6% in placebo, including urinary tract infection [0.8% versus 0.3%] and pneumonia [0.6% versus 0%]), acute hypersensitivity reactions (1.1% versus 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% versus 0%]), depression (1.0% versus 1.0%, including suicidal ideation or attempt [0.6% versus 0.3%]), and cholelithiasis (1.0% versus 0.3%). In Study MS2, serious adverse reactions of appendicitis were also more common in patients who received TYSABRI (0.8% versus 0.2% in placebo).

Table 2 enumerates adverse reactions and selected laboratory abnormalities that occurred in Study MS1 at an incidence of at least 1 percentage point higher in TYSABRI-treated patients than was observed in placebo-treated patients.

Table 2:

Adverse Reactions in Study MS1 (Monotherapy Study) Adverse Reactions (Preferred Term)

B:11.125”

T:10.5”

S:10”

General Headache Fatigue Arthralgia Chest discomfort Other hypersensitivity reactions** Acute hypersensitivity reactions** Seasonal allergy Rigors Weight increased Weight decreased Infection Urinary tract infection Lower respiratory tract infection Gastroenteritis Vaginitis* Tooth infections Herpes Tonsillitis Psychiatric Depression Musculoskeletal/Connective Tissue Disorders Pain in extremity Muscle cramp Joint swelling Gastrointestinal Abdominal discomfort Diarrhea NOS Abnormal liver function test Skin Rash Dermatitis Pruritus Night sweats Menstrual Disorders* Irregular menstruation Dysmenorrhea Amenorrhea Ovarian cyst Neurologic Disorders Vertigo Somnolence Renal and Urinary Disorders Urinary urgency/frequency Urinary incontinence Injury Limb injury NOS Skin laceration Thermal burn

Table 4:

TYSABRI n=627 %

Placebo n=312 %

38 27 19 5 5 4 3 3 2 2

33 21 14 3 2 <1 2 <1 <1 <1

21 17 11 10 9 8 7

17 16 9 6 7 7 5

19

16

16 5 2

14 3 1

11 10 5

10 9 4

12 7 4 1

9 4 2 0

5 3 2 2

4 <1 1 <1

6 2

5 <1

9 4

7 3

3 2 1

2 <1 <1

*Percentage based on female patients only. **Acute versus other hypersensitivity reactions are defined as occurring within 2 hours postinfusion versus more than 2 hours.

In Study MS2, peripheral edema was more common in patients who received TYSABRI (5% versus 1% in placebo).

Table 3:

Adverse Reactions in Studies CD1 and CD2 (Induction Studies)

Adverse Reactions*

General Headache Fatigue Arthralgia Influenza-like illness Acute hypersensitivity reactions Tremor Infection Upper respiratory tract infection Vaginal infections** Viral infection Urinary tract infection Respiratory Pharyngolaryngeal pain Cough Gastrointestinal Nausea Dyspepsia Constipation Flatulence Aphthous stomatitis Skin Rash Dry skin Menstrual Disorder Dysmenorrhea**

TYSABRI n=983 %

Placebo n=431 %

32 10 8 5 2 1

23 8 6 4 <1 <1

22 4 3 3

16 2 2 1

6 3

4 <1

17 5 4 3 2

15 3 2 2 <1

6 1

4 0

2

<1

*Occurred at an incidence of at least 1% higher in TYSABRI-treated patients than placebotreated patients. **Percentage based on female patients only.

Adverse Reactions in Study CD3 (Maintenance Study)

Adverse Reactions*

General Headache Influenza-like illness Peripheral edema Toothache Infection Influenza Sinusitis Vaginal infections** Viral infection Respiratory Cough Gastrointestinal Lower abdominal pain Musculoskeletal and Connective Tissue Back pain Menstrual Disorder Dysmenorrhea**

TYSABRI n=214 %

Placebo n=214 %

37 11 6 4

31 6 3 <1

12 8 8 7

5 4 <1 3

7

5

4

2

12

8

6

3

*Occurred at an incidence of at least 2% higher in TYSABRI-treated patients than placebotreated patients. **Percentage based on female patients only.

Infections Progressive Multifocal Leukoencephalopathy (PML) occurred in three patients who received TYSABRI in clinical trials [see Warnings and Precautions (5.1)]. Two cases of PML were observed in the 1869 patients with multiple sclerosis who were treated for a median of 120 weeks. These two patients had received TYSABRI in addition to interferon beta-1a [see Warnings and Precautions (5.1)]. The third case occurred after eight doses in one of the 1043 patients with Crohn’s disease who were evaluated for PML. In the postmarketing setting, additional cases of PML have been reported in TYSABRI-treated multiple sclerosis and Crohn’s disease patients who were not receiving concomitant immunomodulatory therapy.

In Studies MS1 and MS2 [see Clinical Studies (14.1)], the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebo-treated patients.

The infections were predominately upper respiratory tract infections, influenza, and urinary tract infections. In Study MS1, the incidence of serious infection was approximately 3% in TYSABRItreated patients and placebo-treated patients. Most patients did not interrupt treatment with TYSABRI during infections. The only opportunistic infection in the multiple sclerosis clinical trials was a case of cryptosporidial gastroenteritis with a prolonged course.

In Studies CD1 and CD2 [see Clinical Studies (14.2)], the rate of any type of infection was 1.7 per patient-year in TYSABRI-treated patients and 1.4 per patient-year in placebo-treated patients. In Study CD3, the incidence of any type of infection was 1.7 per patient-year in TYSABRI-treated patients and was similar in placebo-treated patients. The most common infections were nasopharyngitis, upper respiratory tract infection, and influenza. The majority of patients did not interrupt TYSABRI therapy during infections, and recovery occurred with appropriate treatment.

Concurrent use of TYSABRI in CD clinical trials with chronic steroids and/or methotrexate, 6-MP, and azathioprine did not result in an increase in overall infections compared to TYSABRI alone; however, the concomitant use of such agents could lead to an increased risk of serious infections.

In Studies CD1 and CD2, the incidence of serious infection was approximately 2.1% in both TYSABRI-treated patients and placebo-treated patients. In Study CD3, the incidence of serious infection was approximately 3.3% in TYSABRI-treated patients and approximately 2.8% in placebo-treated patients.

In clinical studies for CD, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of TYSABRI-treated patients; some of these patients were receiving concurrent immunosuppressants [see Warnings and Precautions (5.6)]. Two serious non-bacterial meningitides occurred in TYSABRI-treated patients compared to none in placebo-treated patients.

Infusion-related Reactions An infusion-related reaction was defined in clinical trials as any adverse event occurring within two hours of the start of an infusion. In MS clinical trials, approximately 24% of TYSABRI-treated multiple sclerosis patients experienced an infusion-related reaction, compared to 18% of placebotreated patients. In the controlled CD clinical trials, infusion-related reactions occurred in approximately 11% of patients treated with TYSABRI compared to 7% of placebo-treated patients.

Reactions more common in the TYSABRI-treated MS patients compared to the placebo-treated MS patients included headache, dizziness, fatigue, urticaria, pruritus, and rigors. Acute urticaria was observed in approximately 2% of patients. Other hypersensitivity reactions were observed in 1% of patients receiving TYSABRI. Serious systemic hypersensitivity infusion reactions occurred in <1% of patients [see Warnings and Precautions (5.5)]. All patients recovered with treatment and/or discontinuation of the infusion.

Infusion-related reactions that were more common in CD patients receiving TYSABRI than those receiving placebo included headache, nausea, urticaria, pruritus, and flushing. Serious infusion reactions occurred in Studies CD1, CD2, and CD3 at an incidence of <1% in TYSABRI-treated patients.

MS and CD patients who became persistently positive for antibodies to TYSABRI were more likely to have an infusion-related reaction than those who were antibody-negative.

6.2. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to natalizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Patients in Study MS1 [see Clinical Studies (14.1)] were tested for antibodies to natalizumab every 12 weeks. The assays used were unable to detect low to moderate levels of antibodies to natalizumab. Approximately 9% of patients receiving TYSABRI developed detectable antibodies at

least once during treatment. Approximately 6% of patients had positive antibodies on more than one occasion. Approximately 82% of patients who became persistently antibody-positive developed detectable antibodies by 12 weeks. Anti-natalizumab antibodies were neutralizing in vitro.

The presence of anti-natalizumab antibodies was correlated with a reduction in serum natalizumab levels. In Study MS1, the Week 12 pre-infusion mean natalizumab serum concentration in antibody-negative patients was 15 mcg/mL compared to 1.3 mcg/mL in antibody-positive patients. Persistent antibody-positivity resulted in a substantial decrease in the effectiveness of TYSABRI. The risk of increased disability and the annualized relapse rate were similar in persistently antibody-positive TYSABRI-treated patients and patients who received placebo. A similar phenomenon was also observed in Study MS2.

Infusion-related reactions that were most often associated with persistent antibody-positivity included urticaria, rigors, nausea, vomiting, headache, flushing, dizziness, pruritus, tremor, feeling cold, and pyrexia. Additional adverse reactions more common in persistently antibody-positive patients included myalgia, hypertension, dyspnea, anxiety, and tachycardia.

Patients in CD studies [see Clinical Studies (14.2)] were first tested for antibodies at Week 12, and in a substantial proportion of patients, this was the only test performed given the 12-week duration of placebo-controlled studies. Approximately 10% of patients were found to have antinatalizumab antibodies on at least one occasion. Five percent (5%) of patients had positive antibodies on more than one occasion. Persistent antibodies resulted in reduced efficacy and an increase in infusion-related reactions with symptoms that include urticaria, pruritus, nausea, flushing, and dyspnea.

The long-term immunogenicity of TYSABRI and the effects of low to moderate levels of antibody to natalizumab are unknown [see Warnings and Precautions (5.5), Adverse Reactions (6.1)].

6.3. Postmarketing Experience The following adverse reactions have been identified during post approval use of TYSABRI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood disorders: hemolytic anemia 8.

USE IN SPECIFIC POPULATIONS 8.1. Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of TYSABRI in pregnant women. In animal studies, administration of natalizumab during pregnancy produced fetal immunologic and hematologic effects in monkeys at doses similar to the human dose and reduced offspring survival in guinea pigs at doses greater than the human dose. These doses were not maternally toxic but produced the expected pharmacological effects in maternal animals [see Data].

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data Animal Data In developmental toxicity studies conducted in guinea pigs and monkeys, at natalizumab doses up to 30 mg/kg (7 times the recommended human dose based on body weight [mg/kg]), transplacental transfer and in utero exposure of the embryo/fetus was demonstrated in both species.

In a study in which pregnant guinea pigs were administered natalizumab (0, 3, 10, or 30 mg/kg) by intravenous (IV) infusion on alternate days throughout organogenesis (gestation days [GD] 4-30), no effects on embryofetal development were observed.

When pregnant monkeys were administered natalizumab (0, 3, 10, or 30 mg/kg) by IV infusion on alternative days throughout organogenesis (GDs 20-70), serum levels in fetuses at delivery were approximately 35% of maternal serum natalizumab levels. There were no effects on embryofetal development; however, natalizumab-related immunological and hematologic changes were observed in the fetuses at the two highest doses. These changes included decreases in lymphocytes (CD3+ and CD20+), changes in lymphocyte subpopulation percentages, mild anemia, reduced platelet count, increased spleen weights, and reduced liver and thymus weights associated with increased splenic extramedullary hematopoiesis, thymic atrophy, and decreased hepatic hematopoiesis.

In a study in which monkeys were exposed to natalizumab during pregnancy (IV infusion of 30 mg/kg) on alternate days from GD20 to GD70 or GD20 to term, abortions were increased approximately 2-fold compared to controls. In offspring born to mothers administered natalizumab on alternate days from GD20 until delivery, hematologic effects (decreased lymphocyte and platelet counts) were also observed. These effects were reversed upon clearance of natalizumab.

There was no evidence of anemia in these offspring. Offspring exposed in utero and during lactation had a normal immune response to challenge with a T-cell dependent antigen.

In a study in which pregnant guinea pigs were exposed to natalizumab (30 mg/kg IV) on alternate dates during GDs 30-64, a reduction in pup survival was observed.

8.2. Lactation Risk Summary Natalizumab has been detected in human milk. There are no data on the effects of this exposure on the breastfed infant or the effects of the drug on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TYSABRI and any potential adverse effects on the breastfed infant from TYSABRI or from the underlying maternal condition.

8.4. Pediatric Use Safety and effectiveness in pediatric patients with multiple sclerosis or Crohn’s disease below the age of 18 years have not been established. TYSABRI is not indicated for use in pediatric patients.

8.5. Geriatric Use Clinical studies of TYSABRI did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

17.

PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide).

General Counseling Information Counsel patients to understand the risks and benefits of TYSABRI before an initial prescription is written. The patient may be educated by either the enrolled prescriber or a healthcare provider under that prescriber’s direction. INSTRUCT PATIENTS USING TYSABRI TO: • Read the Medication Guide before starting TYSABRI and before each TYSABRI infusion.

• Promptly report any new or continuously worsening symptoms that persist over several days to their prescriber [see Warnings and Precautions (5.1)].

• Inform all of their physicians that they are receiving TYSABRI. • Plan to see their prescriber three months after the first infusion, six months after the first infusion, every six months thereafter, and for at least six months after discontinuing TYSABRI. Progressive Multifocal Leukoencephalopathy Inform patients that Progressive Multifocal Leukoencephalopathy (PML) has occurred in patients who received TYSABRI. Instruct the patient of the importance of contacting their doctor if they develop any symptoms suggestive of PML. Instruct the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Instruct the patient that the progression of deficits usually leads to death or severe disability over weeks or months.

Instruct patients to continue to look for new signs and symptoms suggestive of PML for approximately 6 months following discontinuation of TYSABRI [see Warnings and Precautions (5.1)].

TYSABRI TOUCH® Prescribing Program Advise the patient that TYSABRI is only available through a restricted program called the TOUCH® Prescribing Program. Inform the patient of the following requirements: Patients must read the Medication Guide and sign the Patient Prescriber Enrollment Form. Advise patients that TYSABRI is available only from certified pharmacies and infusion centers participating in the program [see Warnings and Precautions (5.2)].

Herpes Infections Inform patients that TYSABRI increases the risk of developing encephalitis, and meningitis, which could be fatal, and acute retinal necrosis, which could lead to blindness, caused by the family of herpes viruses (e.g., herpes simplex and varicella zoster viruses). Instruct patients to immediately report any possible symptoms of encephalitis and meningitis (such as fever, headache, and confusion) or acute retinal necrosis (such as decreased visual acuity, eye redness, or eye pain) [see Warnings and Precautions (5.3)].

Hepatotoxicity Inform patients that TYSABRI may cause liver injury. Instruct patients treated with TYSABRI to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.4)].

Hypersensitivity Reactions Instruct patients to report immediately if they experience symptoms consistent with a hypersensitivity reaction (e.g., urticaria with or without associated symptoms) during or following an infusion of TYSABRI [see Warnings and Precautions (5.5)].

Immunosuppression/Infections Inform patients that TYSABRI may lower the ability of their immune system to fight infections.

Instruct the patient of the importance of contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.6)].

TYSABRI (natalizumab) Manufactured by: Biogen Inc. Cambridge, MA 02142 USA US License No. 1697 © 2015-2019 Biogen Inc. All rights reserved.

08/2019 U.S. Patent Numbers: 5,840,299; 6,602,503

AANnews · March 2020

March Highlights

6

Stay Ahead of Change at Policy, Practice, and Performance Experiential Learning Area

The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction.

The Vision of the AAN is to be indispensable to our members.

Contact Information American Academy of Neurology 201 Chicago Avenue Minneapolis, MN 55415 Phone: (800) 879-1960 (toll free) (612) 928-6000 (international) Email:

memberservices@aan.com

Website: AAN.com For advertising rates, contact: Eileen R. Henry Wolters Kluwer Health | Medical Research Lippincott, Williams & Wilkins Phone: (732) 778-2261 Email: Eileen.Henry@wolterskluwer.com

Learn how to make your voice heard for you, your patients, and the future of neurology and get answers to some of today’s most pressing practice management related questions at the Policy, Practice, and Performance Experiential Learning Area during the Annual Meeting in Toronto.

21

Promoting Team-based Care: New Patient Scheduling Method

Many advanced practice providers (APPs) are trained as generalists and need on-the-job training to be efficient and effective members of the neurology care team. Read about a successful scheduling method that can improve novice neurology APPs’ learning but does not limit the productivity of the precepting neurologist or APP.

22 AAN Executive Director: Catherine M. Rydell, CAE

Editor-in-Chief: John D. Hixson, MD Managing Editor: Angela M. Babb, MS, CAE, APR Editor: Tim Streeter Writers: Ryan Knoke and Sarah Parsons Designer: Siu Lee Email: aannews@aan.com AANnews® is published monthly by the American Academy of Neurology for its 36,000 members worldwide.

Access this magazine and other AAN publications online at AAN.com.

The American Academy of Neurology ’ s registered trademarks and service marks are registered in the United States and various other countries around the world.

“American Brain Foundation” is a registered service mark of the American Brain Foundation and is registered in the United States.

The inclusion of advertisements and/or promotions of Sponsors and other Internet sites or resources that offer content, goods, or services on the Website does not imply endorsement of the advertised/promoted products or services by AAN.

New Guideline Evaluates Treatments for Sleep Challenges in Children with Autism

The AAN recently published the guideline “Treatment for Insomnia and Disrupted Sleep Behavior in Children and Adolescents with Autism Spectrum Disorder” in Neurology ®.

News Briefs AAN Opposes Proposed Immediate Distribution Policy

Members Share Concerns in Advocacy Survey

The AAN signed a letter along with 135+ other organizations opposing a proposed federal administration policy that would mandate immediate free distribution of peer-reviewed journal articles reporting on federally funded research.

The AAN’s position is that the loss of the thorough review process has the ability to endanger the credibility of the research. Key concerns regarding this order include its potential to negatively impact the advancements of science, innovation, and global competitiveness.

In an annual survey on advocacy priorities, 461 members reported that rising drug costs, regulatory burden associated with prior authorization, and cognitive reimbursement should be top AAN advocacy priorities in 2020. Members also reported that reimbursement, regulatory burden, insurance concerns, and prior authorizations are currently the biggest challenges to their practice or the field of neurology. To give your feedback on advocacy priorities, email advocacy@aan.com. 

AANnews • March 2020 9

New Task Force to Maximize Effectiveness of Patient Resources One of the strategic plan goals of the AAN for 2020 is to increase the reach of AAN resources to enhance patient-centered neurologic care. By doing this, we can help demonstrate the value of neurologists to the public; help members educate their patients on neurologic disease; and leverage the power of patients and their stories to help us advocate on Capitol Hill.

The AAN has a significant inventory of resources for our patients and caregivers, most visibly with the free bimonthly Brain & Life® magazine the Academy provides to our US members to share with their patients, and its companion website, BrainandLife.org.

The magazine has over 312,000 individual subscribers, with more than 184,000 additional copies distributed in members’ offices and clinics and an estimated per-issue reach of 1.6 million. Brain & Life® en Español, launched in April 2018, publishes quarterly and mails to more than 7,200 Spanish-speaking patients with an additional 92,000 copies distributed in members’ offices and clinics. BrainandLife.org, launched in April 2018, is not only the magazine’s online source but the public face of the AAN, educating patients and caregivers about hundreds of neurologic conditions as well as AAN guidelines and advocacy efforts. In 2019, BrainandLife.org had over 21,000 digital subscribers with over 900,000 visits, and more than 100,000 social media followers.

Through Brain & Life and BrainandLife.org, we’ve pointed out new treatments, shared strategies for living well with a neurologic diagnosis and tips for caregivers, promoted awareness of clinical trials, and provided a forum for this unique community to tell their stories and support and inspire one another.

We also have the series of Brain & Life® Books on navigating life with such diseases as Parkinson’s, brain tumor, stroke, multiple sclerosis, epilepsy, ALS, and migraine and other headaches.

Navigating Life with Chronic Pain, published in February, was just added to the series, and a second edition of the Parkinson’s disease book will publish in April.

The power of our public outreach is highly evident at our popular Brain Health Fairs conducted in the host cities of our Annual Meeting, drawing upwards of 3,000 local patients, caregivers, and students to learn more about the diseases that affect their lives, how the quality of their lives can be improved, and how curiosity can lead to new discoveries and careers in neurology. We have established the AAN as a good neighbor in Minneapolis and St. Paul with Bike Helmet Giveaways in the summer, promoting safe practices and brain health awareness.

With the help of our highly respected media and public relations efforts, the AAN Stevens Avitzur brand has been defined as representing the leading experts in all of what we know about the brain, what we yet need to discover, and why new treatments and cures are vital to the health of humanity. Our press releases on the latest science reported in our Neurology ® journals and conferences are regularly covered in major media outlets, as are our guidelines, which include summaries clearly written for patients and caregivers. We have produced patient education videos and public service announcements on numerous brain diseases, and our long-running sports concussion awareness campaign includes a Sports Concussion Toolkit for public use by coaches, athletic directors, and athletes’ parents.

In our advocacy efforts, we have collaborated with patient organizations to bring to Capitol Hill people who are daily fighting the challenges of brain disease so members of Congress can put human faces and stories on staggering statistics. The AAN has helped educate the public through occasional editorials in leading newspapers on reimbursement and advocacy issues that affect our members and patients. We have more formalized education offerings through our "Neuroscience Is...™" programming for K-12 and What Is Neurology? video geared toward medical students that has been supported through a grant from the Conrad N. Hilton Foundation.

F E B R UA RY/M A R C H 2 0 2 0

There is much more that we do that I could talk about. However, as fortunate as we are to have developed and shared so many resources, we need a cohesive, strategic approach that ties them all together with measures for success.

That is why I have created a new Patient and Public Strategy Task Force, chaired by President Elect Orly Avitzur, MD, MBA, FAAN. Dr. Avitzur is well equipped for this job. She is a medical writer and the editor-in-chief of Brain & Life. For 10 years, she served Nav i g a t i ng L i fe as a health editor for Consumer Reports, Huntington’s Disease Understanding Symptoms, Progression, and Prognosis

Your Care Team How to Assemble a Strong Medical Support Network

I never played the don’t-youremember game with my mom.”

—AC TR E S S A N D S I N G E R LY N DA C A R T E R

Exercise How Yoga Helps Those With Traumatic Brain Injury

w it h

C h r on ic Pa i n RO B E R T A . L A V I N , M D, M S SARA E. CLAYTON, PhD LINDSAY A. ZILLIOX, MD

10

AANnews • March 2020

Toronto

and as its medical director from 2015 to 2018. Our Academy Vice President Ann H. Tilton, MD, FAAN, one of the leading experts in child neurology, will serve as vice chair.

This task force is charged with determining the following: How can we better engage/inform our patients and the public with AAN resources currently available?

How can we mobilize patients/public to advocate for issues critical to our profession through current products and new initiatives?

How can we collaborate with strategic partner organizations to accomplish AAN goals?

Provide a one-, three-, and five-year plan along with metrics for success.

The AAN has been challenged by the fact that it represents the needs and aspirations of many different subspecialists who treat people affected by hundreds of different types of brain disease, as well as the neuroscientists working to eradicate these disorders. Yet, the growing prevalence and public discourse regarding such diseases as autism in our very young, Alzheimer’s in our very old, and concussion in those in between has reminded people of the fragility of the body’s most important and supremely mysterious organ. This is the right time to take stock of where we are, what we have accomplished, and what we need to do to help better fulfill the needs of our patients and build our brand with the public as the champions of brain health care. 

The World’s Largest Neurology Meeting Is Coming to One of the World’s Most Diverse Cities Save when you register by April 2

AAN.com/view/AM20

James C. Stevens, MD, FAAN President, AAN jstevens@aan.com @JimStevensMD on Twitter

April 25 – May 1 • Toronto, Canada

Conferences & Community

Chairs’ Can’t-miss Picks for the Annual Meeting Each month leading up to the 2020 Annual Meeting, we’re asking AAN leaders tasked with planning the meeting to weigh in on can’t-miss events from their committee or subcommittee, as well as what they, personally, value most about the meeting itself.

Every year, scientific plenary sessions bring the most exciting developments to the thousands of attendees, including the cutting-edge neuroscience, the latest clinical trials across the spectrum of neurological diseases, hot topics in neurology, scientific advances that have already entered our clinical practice, and of course the controversies in neurology! I am always in the front row in those sessions, learning what’s new and am inspired about what’s yet to come! I also highly recommend our Neuroscience in the Clinic (NIC) programming, the Invited Science sessions, and of course everyone’s favorite—the original science presented in scientific platforms and electronic posters. One thing is for sure, there is no shortage of exciting science.

Despite my many subspecialty research commitments, over the years the AAN’s Annual Meeting has become my most important conference to attend. I see it as a 'full immersion' experience for a subspecialty-trained stroke neurologist and clinician-scientist like me, where not only I reconnect with the entire spectrum of neurological science but also have the opportunity to engage with my neurology community and participate in activities (such as leadership development, mentorship, and well-being strategies, to name a few) that make our profession so unique and dynamic. I invite all my colleagues and friends to experience these opportunities at the Annual Meeting— and I’m looking forward to seeing you all in Toronto!

Natalia S. Rost, MD, MPH, FAHA, FAAN Chair, AAN Science Committee

Stronger Business Administrators Make a Stronger Practice Each member of the neurology practice is essential to high-quality patient care. Why not give your business administrators an edge with access to the world’s best neurology resources and education to help them better reduce costs and increase revenue for your practice?

For only $275, AAN member benefits can help your business administrators: Improve your practice’s efficiency with exclusive access to the 2020 Practice Management webinar series Be the first to know the latest news impacting your practice and the health care landscape with AAN publications including Neurology® Clinical Practice*, Neurology Today ®, and AANnews®*

Access member-only resources including quality improvement resources, payment and reform tools, clinical practice guidelines, and online education programs Connect with a network of administrators, neurologists, and neuroscience professionals worldwide $120 membership will offer the same membership benefits, excluding access to the 2020 Practice Management webinar series, online education programs, and Neurology Today in print.

We know how important strong business administrators are to help a neurology practice stand out from the competition, so view a full listing of exclusive business administrator benefits and sign yours up today at AAN.com/view/CareTeam. *International members receive digital access only. 

12

AANnews • March 2020

Annual Meeting Gets Physical Attendees of this spring’s Annual Meeting will have plenty of opportunities to get out and active—for fun and good causes— with a number of physical and wellness activities designed to challenge both body and soul.

Step Challenge

Research is sponsored by Eisai, Inc. and Genentech, A Member of the Roche Group.

Join the fun and keep active all week! Simply download the Heka Health App—available for iOS and Android and select the “American Academy of Neurology” on the dropdown menu to compete for prizes with your fellow attendees to see who gets the most total steps in for the week. Even if you are only attending the Annual Meeting for a couple of days, the Step Challenge lets you compete from anywhere, even after you leave the meeting. Steps can be tracked using Garmin, iPhone, Android, Apple watch, or Fitbit.

The Great Neuro Race

Saturday, April 25–Friday, May 1

Run/Walk for Brain Research Tuesday, April 28, 6:30 a.m.

Start the day in a healthy and philanthropic way. Show your support for brain research while enjoying this early morning run/walk along the beautiful Toronto waterfront. Registration is $50 per participant and all funds go to support research. Add the Run/Walk to your Annual Meeting experience by signing up through Annual Meeting registration. The Run/Walk for Brain

Thursday, April 30

Pick your favorite category and then hit the streets of Toronto for fun-filled mental and physical team challenges using clues to figure out the next step in the game. Create your own team of up to five friends or let us assign you to a team for enhanced networking opportunities. Choose from film, museums, food, or extreme sports categories. Registration is free to Annual Meeting attendees and on a first-come, first-served basis until spots are filled, after which a waiting list will be created.

Email Lydia Campbell at lcampbell@aan.com to sign up.

Learn more about Annual Meeting physical and wellness activities at AAN.com/PhysicalWellness. 

April 25 – May 1 • Toronto, Canada

Conferences & Community

Wrap up Annual Meeting with Food, Fun, and Laughs with Second City Celebrate the close of an amazing week with the infamously hilarious Second City Improv while enjoying plenty of delicious food, beverages, and camaraderie on Friday, May 1, from 5:00 p.m. to 7:00 p.m. in the Metro Toronto Convention Centre.

Each registered Annual Meeting attendee receives a free ticket to the event.

Additional guest tickets can be purchased for $50 each at AAN.com/view/AM20.

Seating is limited. 

April 25 – May 1 • Toronto, Canada

Stay Ahead of Change at Policy, Practice, and Performance Experiential Learning Area Learn how to make your voice heard for you, your patients, and the future of neurology and get answers to some of today’s most pressing practice management related questions at the Policy, Practice, and Performance Experiential Learning Area during the 2020 Annual Meeting in Toronto. Don’t forget to wear green on Tuesday, April 28, to promote Neurology on the Hill during Wear Green Tuesday!

Stop by to: Catch presentations on a variety of topics including ultra-high neurology drug prices, E/M and EEG coding changes, business operations, and more.

Visit the Polling Station to tell us what matters most to you—you can make a difference!

Find out how you can get involved and initiate your own advocacy efforts. Learn about exciting advocacy programs including Neurology on the Hill, Palatucci Advocacy Leadership Forum, and the Advocacy Action Center.

Get answers from staff and member experts on some of neurology’s most pressing challenges today.

Understand how the Axon Registry ® can improve your practice, and if you’ve already been onboarded in Axon, learn how to maximize your enrollment.

Get firsthand guidance on AAN resources like guidelines and quality measures.

Snap a photo at our selfie station and upload it to social media to promote #AANadvocacy.

Learn more about this and other Experiential Learning Areas at AAN.com/view/ELA 

14

AANnews • March 2020

Science, Knowledge, and Recognition Intersect at Research Experiential Learning Area continued from cover Look for: Research Presentations Enjoy presentations throughout the week on a variety of research topics, such as finding a research mentor, working with the Institutional Review Board, how to include underrepresented populations in research, and more.

Look for presentations entirely in Spanish, too.

Scientific Sessions Learn about the latest abstracts in an oral format with the opportunity to ask the researcher questions. Look for sessions on Global Health, Autonomic Disorders, Neuro-rehabilitation, and Pain and Palliative Care.

Don’t Miss National Institutes of Health Day Tuesday, April 28 Join Walter J. Koroshetz, MD; Richard Benson, MD, PhD; and Clinton B. Wright, MD, MS, along with other partners from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute on Aging for a full day of programming with updates from each organization. 

Awards Stop by to see who has won an award—including the recipients of the Mitchell B. Max Award for Neuropathic Pain and Irwin Schatz Award in Autonomic Disorders— on our research award displays and stay to listen to presentations from select award recipients.

Learn more about this and other Experiential Learning Areas at AAN.com/view/ELA. 

April 25 – May 1 • Toronto, Canada

AANnews • March 2020 15

Conferences & Community

Synapse Continues to See Growth, Engagement SynapseSM Online Communities continued to experience steady growth and engagement over the past year, ending 2019 with 21,181 members—more than half of AAN membership.

As the AAN's exclusive online community, Synapse serves as a platform where members from the Academy’s more than 45 sections, consortiums, and open communities come together to engage in conversation; exchange ideas; and share scientific, practice, and professional insights.

For more information about AAN Sections and Synapse, visit AAN.com/view/sections. 

Cascino to Receive President’s Award Gregory D. Cascino, MD, FAAN, of the Mayo Clinic, has been named recipient of the 2020 AAN President’s Award. Cascino was chosen because of his leadership as chair of the Member Engagement Committee and the Academy’s success in attaining a record number of members, now more than 36,000. 

Ko Appointed New Editor-in-Chief of AANnews President James C. Stevens, MD, FAAN, has appointed Melissa W. Ko, MD, FAAN, to succeed John D. Hixson, MD, as editor-in-chief of AANnews®, starting in April 2020.

Ko is a five-time participant in the AAN’s Neurology on the Hill and is a 2010 graduate of the Palatucci Advocacy Leadership Forum (PALF), served on the task force for Gender Pay Disparity, and was a member of the Government Relations Committee. She currently serves on the BrainPAC Executive Committee and the Member Engagement Committee. She is a member of the Neuro-ophthalmology/Neuro-otology Section, PALF Graduates Community, and the Women's Issues in Neurology

16

AANnews • March 2020

Section, and has been a member of the AAN since 2005.

Ko graduated from University of Rochester School of Medicine in 2003 and completed her neurology and fellowship training in neuroophthalmology at the University of Pennsylvania. She recently joined the faculty of the Indiana University School of Medicine as associate professor of neurology and ophthalmology and serves as the director of clinical operations for the Department of

Neurology and the Eugene and Marilyn Glick Eye Institute in Indianapolis, IN. Previously, she was on faculty at SUNY Upstate Medical University in Syracuse, NY.

Ko

The AAN welcomes Ko to her new role and thanks Hixson for his leadership over the past decade! 

2020 Sports Concussion Conference Coming to Minneapolis in July continued from cover

culture, cuisine, seven professional sports teams, and seven major sports arenas, including U.S. Bank Stadium, home to the 2018 Super Bowl and 2019 Final Four.

Attendees can once again expect to find top experts presenting the latest scientific information and best practices for all clinicians, scientists, and care teams involved in the prevention, diagnosis, and management of sport-related concussion at the youth, high school, collegiate, and professional levels. Abstract submissions open later this month at AAN.com/SCC, where additional information and updates on conference programming and registration will be available later this month. 

SPORTS CONCUSSION JULY 17–19, 2020 MINNEAPOLIS, MN

PODCAST

CONFERENCE

Neurology ® Podcast:

20 Minutes Pack a Punch!

Subscribe and download the latest podcast at Neurology.org/podcast

AANnews • March 2020 17

Tools & Resources

Know How Benchmarking Quality Measures Affects Your MIPS Payments The requirements for Quality Payment Program (QPP) Merit-based Incentive Payment System (MIPS) administered by the Centers for Medicare & Medicaid Services (CMS) are complex. AAN members may not be aware of how CMS has benchmarked quality measure performance and the impact measure benchmarks have on individual payment.

What is benchmarking?

Do Axon Registry measures have MIPS benchmarks?

Benchmarking is a method of evaluating performance between organizations and individual providers. For MIPS, CMS sets the benchmark annually for every quality measure. Each submission method will have specific benchmarks to meet the requirements.

Providers that are reporting on the same measure will have different benchmarks depending on if they are reporting via claims, electronic health record (EHR) vendor, or Qualified Clinical Data Registry (QCDR) like the Axon Registry®.

Some Axon Registry measures have benchmarks, but not all do. Points awarded will vary as a result.

How many points can I earn in the quality component?

For the MIPS quality category, providers should be reporting six measures and at least one of these measures should be an outcome measure. If the participant does not use an outcome measure, a high priority measure is required. CMS will award between zero to 10 points for each MIPS measure depending on the participant’s performance.

The quality category is weighted as 45 percent of the total MIPS score. Bonus points are given if more outcome or high priority measures are submitted or if end-to-end reporting is used.

End-to-end reporting means submitting MIPS data via EHR or registry vendor. For a positive payment adjustment in PY 2020, providers will need to attain over 45 points across all four MIPS categories.

18

How many points can I earn for a benchmarked Axon Registry measure?

The points available will vary for each measure. Currently there are multiple Axon Registry measures with benchmark data. A few examples of measures and potential points to be awarded are included below. The decile corresponds with the points awarded for a measure assuming data completeness thresholds are met. If the data completeness threshold is not met zero points are awarded. In 2020, the data completeness threshold for Axon Registry participants requires reporting on 70 percent of the individual clinician’s patients across all payers for the performance period.

Where can I find Axon Registry measure benchmarks?

The full list of 2020 quality benchmarks are available at qpp.cms.gov/about/resource-library. The full benchmark files include several scoring examples. CMS has more information on MIPS requirements at qpp.cms.gov.

For more information on how to join the Axon Registry, visit AAN.com/view/Axon or contact registry@aan.com. 

Measure Title

Decile 3

Decile 4

Decile 5

Decile 6

Decile 7

Decile 8

Decile 9

Decile 10

Average Performance Rate

Medication Prescribed for Acute Migraine Attack

8.97– 39.71

39.72– 53.32

53.33– 65.61

65.62– 75.99

76.0– 83.68

83.69– 87.4

87.41– 91.99

>=92

63.033

Exercise and Appropriate Physical Activity Counseling for Patients with MS

17.25– 38.78

38.79– 56.89

56.90– 78.44

78.45– 93.52

93.53– 99.99

—

—

100

73.063

Querying About Symptoms of Autonomic Dysfunction for Patients with Parkinson's Disease

0.82– 3.59

3.60– 27.48

27.49– 78.66

78.67– 94.38

94.39– 98.64

98.65– 99.99

—

100

61.51

Parkinson's Disease: Psychiatric Symptoms Assessment for Patients with Parkinson's Disease (QPP #290)

3.5– 9.37

9.38– 22.94

22.95– 51.84

51.85– 99.99

­—

—

—

100

58.069

AANnews • March 2020

Initiate Your Quality Improvement Project Now Initiating and executing a quality improvement project as a resident can be daunting. Start now by identifying the right quality improvement project to meet your residency program requirements. The AAN has quality improvement resources designed to help both program directors and residents succeed. Visit AAN.com/policy-and-guidelines/quality to learn more about the following resources: Quality Measures—The AAN has measures for inpatient, outpatient, child, adult, and geriatric neurology populations.

With over 100 to choose from covering epilepsy, multiple sclerosis, stroke, neuropathy, movement disorders, and more, residents could identify one quality measure to institute and track to drive performance improvement.

Patient Reported Outcomes—Implementing a new, validated scale or tool in practice can provide valuable insights into patient priorities and care goals. The AAN has summarized some of the more commonly used freely available tools for neurology.

Quality Toolkit—After identifying a quality measure, residents can learn the basic steps to improvement or focus in on driving improvement in safety, effectiveness, efficiency, and patient-centered care.

Program Director Resources—This toolkit draws attention to AAN resources to help program directors meet Accreditation Council for Graduate Medical Education (ACGME) requirements for patient care, practice-based learning and improvement, interpersonal communication, and systems-based practice. 

QUALITY TOOLKIT QUALITY MEASURES PROGRAM DIRECTOR RESOURCES PATIENT REPORTED OUTCOMES

Are You Getting Your AANe-news?

Don’t miss the latest news headlines from your Academy! As an exclusive member benefit, you should be receiving AANe-news™ the second and fourth Wednesday of each month if your email address is on file. If not, be sure to set your email filter to accept mailer@aan.com as a friendly address. Or update your email address at AAN.com/MemberProfile.

It’s Not Spam... It’s AANe-news!

AANnews • March 2020 19

Tools & Resources

Solo and Small Practice Community Coming to Synapse Launching this month, physicians, advanced practice providers, and business administrators working in small and solo practice settings will have a SynapseSM online community to call home.

Members of the new Small and Solo Practice Synapse Community will be able to reach out and engage colleagues in similar practice settings, answering a need made clear during visits by the AAN’s Practice Ambassador Program regarding the unique challenges of solo and small practices. Participants now can ask questions and share expertise with colleagues who truly understand the dynamics of the small and solo workplace. And, of course, members can also join other communities of interest to reach an even broader audience.

Since its debut in 2016, Synapse has grown to over 50 communities and more than 21,000 members. This member-only benefit allows participants to: Interact with others who share the same specialty and practice interests Share expertise and real-world solutions to practice, patient care, and other issues facing the neurology community Download and share documents in the community’s digital library Provide feedback on section-relevant AAN programs and services Administrators and advanced practice providers can join the Academy to take advantage of this networking opportunity and other relevant benefits. To join or renew these memberships, visit AAN.com/view/CareTeam.

MEM: 18 BUSM Recruitment Ad—Half Page Horizontal> AN Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C

To join this new online community, visit Synapse.AAN.com/home.

For more information, contact practice @aan.com. 

STRONGER BUSINESS ADMINISTRATORS MAKE A MORE EFFICIENT PRACTICE Strengthen your BUSINESS ADMINISTRATOR’S knowledge and skills in neurology with special, reduced rate AAN memberships.

Sign your team up today at

AAN.com/view/careteam.

Academy Efforts Help Smooth Payer Relationships, Provide Member Resources payment rates for the TC codes for their geographic Working with public and private payers can be jurisdiction. perceived as an ominous experience by any physician.

But the AAN has neurologists’ backs thanks to the The AAN’s payer relations team contacted several AAN Coding and Payment Policy Subcommittee, public and private payers to raise awareness of chaired by Board Member Elaine C. Jones, MD, FAAN, the new code set and request information on when and a dedicated payer relations staff. In numerous medical policy updates can be expected and when ways, their efforts help support members as well as claims will be accepted with the new codes. The Jones payer organizations. Their work includes reviewing Academy received several positive responses from draft medical policies and providing feedback from commercial payers willing to engage with the AAN. AAN subject matter experts to help payer organizations create Many payers indicated they would not update their policies on and/or modify medical policies and fully understand how a long-term EEG monitoring until early in 2020, and the Academy given service is used by neurologists. Academy staff assists continues to monitor payers’ medical policies for changes. members in understanding why coverage might have been The AAN also is increasing engagement with creation of a denied and helps them navigate the next steps. quarterly newsletter to payers. Our first edition was distributed “The way we practice medicine continues to change in early 2020 to educate payers on coding changes, new and dramatically from coding changes in new and old service lines, emerging therapies, and AAN resources. The electronic to emphasizing quality over quantity, and to a more systemresource includes direct links to AAN guidelines, quality focused care model that increases access and decreases measure sets, and guidelines companion pieces that can be cost,” said Jones. “The AAN is actively engaged in fighting used in creating or modifying medical policies. for processes that work for neurologists, and in educating New resources have been created for AAN members as members on navigating these changes successfully. If you ever well, including an Insurance Verification Checklist and Prior have any questions or concerns the AAN is here to help” Authorization Checklist. Both resources are available online When significant coding changes occur, the AAN reaches out at AAN.com/view/PracticeResources. Check back often as to payers to educate them on the changes. One example is the additional tools will be added as member needs are identified.

Long-term EEG monitoring service code changes which were The Academy also has created resources for members to find effective January 1, 2020. The Centers for Medicare & Medicaid their regional MAC and tools for working with them, available at Services assigned contractor pricing to the codes reported AAN.com/view/MedicareNews. for the technical component (TC) of the services, which Members who have any concerns or issues with coverage are added another level of complexity. As a result, each Medicare urged to contact AAN staff at practice@aan.com.  Administrative Contractor (MAC) is responsible for establishing

Report MIPS Data by End of March The Centers for Medicare & Medicaid Services (CMS) Quality Payment Program Merit-based Incentive Payment System (MIPS) 2019 Performance Year (PY) submission window will close on March 31, 2020, for most eligible clinicians (ECs).

ECs can report via multiple mechanisms including CMS Web Interface, a Qualified Clinical Data Registry (QCDR, such as the AAN’s Axon Registry ®), electronic health records, or other registry.

For solo and small practice ECs reporting via Part B Claims data, the window previously closed in February 2020. CMS anticipates performance feedback for the 2019 PY will be available on July 1, 2020. Full details of CMS’s timelines can be found at qpp.cms.gov/about/deadlines.

Members are encouraged to identify a reporting mechanism for the 2020 PY now.

The AAN’s Axon Registry is a CMS QCDR and a free benefit for US members.

Learn more by contacting registry @aan.com. 

AANnews • March 2020 21

For adults.

Not actual patients.

INDICATION MAYZENT® (siponimod) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

IMPORTANT SAFETY INFORMATION Contraindications • Patients with a CYP2C9*3/*3 genotype • In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure • Presence of Mobitz type II second-degree, third-degree atrioventricular block, or sick sinus syndrome, unless patient has a functioning pacemaker Infections: MAYZENT may increase risk of infections with some that are serious in nature.

Life-threatening and rare fatal infections have occurred.

Before starting MAYZENT, review a recent complete blood count (CBC) (ie, within 6 months

or after discontinuation of prior therapy). Delay initiation of treatment in patients with severe active infections until resolved. Employ effective treatments and monitor patients with symptoms of infection while on therapy.

Consider discontinuing treatment if patient develops a serious infection.

Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator. Rare cases of CM have occurred with MAYZENT. If CM is suspected, MAYZENT should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.

No cases of progressive multifocal leukoencephalopathy (PML) were reported in MAYZENT clinical trials; however, they have been observed in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator and other multiple sclerosis (MS) therapies. If PML is suspected, MAYZENT should be discontinued.

Cases of herpes viral infection, including one case of reactivation of varicella zoster virus leading to varicella zoster meningitis, have

Please see additional Important Safety Information and Brief Summary of full Prescribing Information on the following pages.

THE TIME IS NOW MAYZENT® is the first and only oral DMT studied and proven to delay disability progression in a more progressed RMS patient population (mean EDSS score of 5.4).1-3 Get patients started at mayzenthcp.com

DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; RMS=relapsing multiple sclerosis.

IMPORTANT SAFETY INFORMATION (CONT) been reported. Patients without a confirmed history of varicella zoster virus (VZV) or without vaccination should be tested for antibodies before starting MAYZENT. If VZV antibodies are not present or detected, then VZV immunization is recommended and MAYZENT should be initiated 4 weeks after vaccination.

Use of live vaccines should be avoided while taking MAYZENT and for 4 weeks after stopping treatment.

Caution should be used when combining treatment (ie, anti-neoplastic, immunemodulating, or immunosuppressive therapies) due to additive immune system effects.

Macular Edema: In most cases, macular edema occurred within 4 months of therapy. Patients with history of uveitis or diabetes are at an increased risk.

Before starting treatment, an ophthalmic evaluation of the fundus, including the macula, is recommended and at any time if there is a change in vision. The use of MAYZENT in patients with macular edema has not been evaluated; the potential risks

and benefits to the individual patient should be considered.

Bradyarrhythmia and Atrioventricular Conduction Delays: Prior to initiation of MAYZENT, an ECG should be obtained to determine if preexisting cardiac conduction abnormalities are present. In all patients, a dose titration is recommended for initiation of MAYZENT treatment to help reduce cardiac effects.

MAYZENT was not studied in patients who had: • In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization • New York Heart Association Class II-IV heart failure • Cardiac conduction or rhythm disorders, including complete left bundle branch block, sinus arrest or sino-atrial block, symptomatic bradycardia, sick sinus syndrome, Mobitz type II second-degree AV-block or higher-grade AV-block (either history or observed at screening), unless patient has a functioning pacemaker

IMPORTANT SAFETY INFORMATION (CONT) Bradyarrhythmia and Atrioventricular Conduction Delays (cont): MAYZENT was not studied in patients who had: • Significant QT prolongation (QTc greater than 500 msec) • Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs Reinitiation of treatment (initial dose titration, monitoring effects on heart rate and AV conduction [ie, ECG]) should apply if ≥4 consecutive daily doses are missed.

Respiratory Effects: MAYZENT may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy if clinically warranted.

Liver Injury: Elevation of transaminases may occur in patients taking MAYZENT. Before starting treatment, obtain liver transaminase and bilirubin levels. Closely monitor patients with severe hepatic impairment. Patients who develop symptoms suggestive of hepatic dysfunction should have liver enzymes checked, and MAYZENT should be discontinued if significant liver injury is confirmed.

Increased Blood Pressure: Increase in systolic and diastolic pressure was observed about 1 month after initiation of treatment and persisted with continued treatment. During therapy, blood pressure should be monitored and managed appropriately.

Fetal Risk: Based on animal studies, MAYZENT may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during and for 10 days after stopping MAYZENT therapy.

Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a sphingosine 1-phosphate (S1P) receptor modulator. Such events have not been reported for patients treated with MAYZENT

in clinical trials. If patients develop any unexpected neurological or psychiatric symptoms, a prompt evaluation should be considered. If PRES is suspected, MAYZENT should be discontinued.

Unintended Additive Immunosuppressive Effects From Prior Treatment or After Stopping MAYZENT: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects.

Initiating treatment with MAYZENT after treatment with alemtuzumab is not recommended.

After stopping MAYZENT therapy, siponimod remains in the blood for up to 10 days. Starting other therapies during this interval will result in concomitant exposure to siponimod.

Lymphocyte counts returned to the normal range in 90% of patients within 10 days of stopping therapy. However, residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3-4 weeks after the last dose.

Use of immunosuppressants within this period may lead to an additive effect on the immune system, and therefore, caution should be applied 3-4 weeks after the last dose of MAYZENT. Severe Increase in Disability After Stopping MAYZENT: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of an S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping MAYZENT treatment, thus patients should be monitored upon discontinuation.

Most Common Adverse Reactions: Most common adverse reactions (>10%) are headache, hypertension, and transaminase increases.

Please see additional Important Safety Information on the previous pages, and Brief Summary of full Prescribing Information on adjacent pages.

References: 1. Mayzent [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; March 2019.

2. Data on file. First and only progressing RMS treatment. Novartis Pharmaceuticals Corp; July 2019.

3. Kappos L, Bar-Or A, Cree BAC, et al; for the EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet.

2018;391(10127):1263-1273.

MAYZENT and the MAYZENT logo are registered trademarks of Novartis AG.

Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936-1080

© 2020 Novartis

1/20

MZT-1385640

MAYZENT® (siponimod) tablets, for oral use Initial U.S. Approval: 2019 BRIEF SUMMARY: Please see package insert for full prescribing information.

1 INDICATIONS AND USAGE MAYZENT is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsingremitting disease, and active secondary progressive disease, in adults.

4 CONTRAINDICATIONS MAYZENT is contraindicated in patients who have: • A CYP2C9*3/*3 genotype [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.5) in the full prescribing information] • In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure • Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker [see Warnings and Precautions (5.3)] 5 WARNINGS AND PRECAUTIONS 5.1 Infections Risk of Infections MAYZENT causes a dose-dependent reduction in peripheral lymphocyte count to 20%-30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. MAYZENT may therefore increase the risk of infections, some serious in nature [see Clinical Pharmacology (12.2) in the full prescribing information]. Life-threatening and rare fatal infections have occurred in association with MAYZENT. In Study 1 [see Clinical Studies (14) in the full prescribing information], the overall rate of infections was comparable between the MAYZENTtreated patients and those on placebo (49.0% vs. 49.1% respectively).

However, herpes zoster, herpes infection, bronchitis, sinusitis, upper respiratory infection, and fungal skin infection were more common in MAYZENT-treated patients. In Study 1, serious infections occurred at a rate of 2.9% in MAYZENT-treated patients compared to 2.5% of patients receiving placebo.

Before initiating treatment with MAYZENT, results from a recent complete blood count (i.e., within 6 months or after discontinuation of prior therapy) should be reviewed.

Initiation of treatment with MAYZENT should be delayed in patients with severe active infection until resolution. Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3-4 weeks after discontinuation of MAYZENT, vigilance for infection should be continued throughout this period [see Warnings and Precautions (5.11)].

Effective diagnostic and therapeutic strategies should be employed in patients with symptoms of infection while on therapy. Suspension of treatment with MAYZENT should be considered if a patient develops a serious infection.

Cryptococcal Infections Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections have been reported with another sphingosine 1-phosphate (S1P) receptor modulator. Rare cases of CM have also occurred with MAYZENT. Physicians should be vigilant for clinical symptoms or signs of CM. Patients with symptoms or signs consistent with a cryptococcal infection should undergo prompt diagnostic evaluation and treatment.

MAYZENT treatment should be suspended until a cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.

Herpes Viral Infections Cases of herpes viral infection, including one case of reactivation of VZV infection leading to varicella zoster meningitis, have been reported in the development program of MAYZENT. In Study 1, the rate of herpetic infections was 4.6% in MAYZENT-treated patients compared to 3.0% of patients receiving placebo. In Study 1, an increase in the rate of herpes zoster infections was reported in 2.5% of MAYZENT-treated patients compared to 0.7% of patients receiving placebo. Patients without a healthcare professional confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating MAYZENT (see Vaccinations below).

Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of

vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

No cases of PML have been reported in MAYZENT-treated patients in the development program; however, PML has been reported in patients treated with a S1P receptor modulator and other multiple sclerosis (MS) therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). Physicians should be vigilant for clinical symptoms or MRI findings that may be suggestive of PML. MRI findings may be apparent before clinical signs or symptoms. If PML is suspected, treatment with MAYZENT should be suspended until PML has been excluded.

Prior and Concomitant Treatment with Anti-neoplastic, Immune-Modulating, or Immunosuppressive Therapies Anti-neoplastic, immune-modulating, or immunosuppressive therapies (including corticosteroids) should be coadministered with caution because of the risk of additive immune system effects during such therapy [see Drug Interactions (7.1)].

Vaccinations Patients without a healthcare professional confirmed history of chickenpox or without documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating MAYZENT treatment. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with MAYZENT, following which initiation of treatment with MAYZENT should be postponed for 4 weeks to allow the full effect of vaccination to occur.

The use of live attenuated vaccines should be avoided while patients are taking MAYZENT and for 4 weeks after stopping treatment [see Drug Interactions (7.1)].

Vaccinations may be less effective if administered during MAYZENT treatment. MAYZENT treatment discontinuation 1 week prior to and until 4 weeks after a planned vaccination is recommended.

5.2 Macular Edema Macular edema was reported in 1.8% of MAYZENT-treated patients compared to 0.2% of patients receiving placebo. The majority of cases occurred within the first four months of therapy.

An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking MAYZENT. Continuation of MAYZENT therapy in patients with macular edema has not been evaluated. A decision on whether or not MAYZENT should be discontinued needs to take into account the potential benefits and risks for the individual patient.

Macular Edema in Patients with a History of Uveitis or Diabetes Mellitus Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during MAYZENT therapy. The incidence of macular edema is also increased in MS patients with a history of uveitis. In the clinical trial experience in adult patients with all doses of MAYZENT, the rate of macular edema was approximately 10% in MS patients with a history of uveitis or diabetes mellitus versus 2% in those without a history of these diseases. In addition to the examination of the fundus, including the macula, prior to treatment, MS patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations.

5.3 Bradyarrhythmia and Atrioventricular Conduction Delays Since initiation of MAYZENT treatment results in a transient decrease in heart rate and atrioventricular conduction delays, an up-titration scheme should be used to reach the maintenance dosage of MAYZENT [see Dosage and Administration (2.2, 2.3) and Clinical Pharmacology (12.2) in the full prescribing information].

MAYZENT was not studied in patients who had: • In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization • New York Heart Association Class II-IV heart failure • Cardiac conduction or rhythm disorders, including complete left bundle branch block, sinus arrest or sino-atrial block, symptomatic bradycardia, sick sinus syndrome, Mobitz type II second degree AV-block or higher grade AV-block (either history or observed at screening), unless patient has a functioning pacemaker • Significant QT prolongation (QTc greater than 500 msec) • Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs [see Drug Interactions (7.2)] Reduction in Heart Rate After the first titration dose of MAYZENT, the heart rate decrease starts within an hour, and the Day 1 decline is maximal at approximately 3-4 hours. With continued up-titration, further heart rate decreases are

seen on subsequent days, with maximal decrease from Day 1-baseline reached on Day 5-6. The highest daily post-dose decrease in absolute hourly mean heart rate is observed on Day 1, with the pulse declining on average 5-6 bpm. Post-dose declines on the following days are less pronounced. With continued dosing, heart rate starts increasing after Day 6 and reaches placebo levels within 10 days after treatment initiation.

In Study 1, bradycardia occurred in 4.4% of MAYZENT-treated patients compared to 2.9% of patients receiving placebo. Patients who experienced bradycardia were generally asymptomatic. Few patients experienced symptoms, including dizziness or fatigue, and these symptoms resolved within 24 hours without intervention [see Adverse Reactions (6.1)]. Heart rates below 40 bpm were rarely observed.

Atrioventricular Conduction Delays Initiation of MAYZENT treatment has been associated with transient atrioventricular conduction delays that follow a similar temporal pattern as the observed decrease in heart rate during dose titration. The AV conduction delays manifested in most of the cases as first-degree AV block (prolonged PR interval on ECG), which occurred in 5.1% of MAYZENTtreated patients and in 1.9% of patients receiving placebo in Study 1.

Second-degree AV blocks, usually Mobitz type I (Wenckebach), have been observed at the time of treatment initiation with MAYZENT in less than 1.7% of patients in clinical trials. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, rarely required treatment with atropine, and did not require discontinuation of MAYZENT treatment.

If treatment with MAYZENT is considered, advice from a cardiologist should be sought: • In patients with significant QT prolongation (QTc greater than 500 msec) • In patients with arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs [see Drug Interactions (7.2)] • In patients with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension • In patients with a history of second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sino-atrial heart block [see Contraindications (4)] Treatment-Initiation Recommendations • Obtain an ECG in all patients to determine whether preexisting conduction abnormalities are present.

• In all patients, a dose titration is recommended for initiation of MAYZENT treatment to help reduce cardiac effects [see Dosage and Administration (2.2, 2.3) in the full prescribing information].

• In patients with sinus bradycardia (HR less than 55 bpm), first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure with onset > 6 months prior to initiation, ECG testing and first-dose monitoring is recommended [see Dosage and Administration (2.1, 2.4) in the full prescribing information].

• Since significant bradycardia may be poorly tolerated in patients with history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, or severe untreated sleep apnea, MAYZENT is not recommended in these patients. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring strategy.

• Use of MAYZENT in patients with a history of recurrent syncope or symptomatic bradycardia should be based on an overall benefit-risk assessment. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring.

• Experience with MAYZENT is limited in patients receiving concurrent therapy with drugs that decrease heart-rate (e.g., beta-blockers, calcium channel blockers - diltiazem and verapamil, and other drugs that may decrease heart rate, such as ivabradine and digoxin). Concomitant use of these drugs during MAYZENT initiation may be associated with severe bradycardia and heart block.

• For patients receiving a stable dose of a beta-blocker, the resting heart rate should be considered before introducing MAYZENT treatment. If the resting heart rate is greater than 50 bpm under chronic beta-blocker treatment, MAYZENT can be introduced. If resting heart rate is less than or equal to 50 bpm, beta-blocker treatment should be interrupted until the baseline heart-rate is greater than 50 bpm.

Treatment with MAYZENT can then be initiated and treatment with a beta-blocker can be reinitiated after MAYZENT has been up-titrated to the target maintenance dosage [see Drug Interactions (7.3)].

• For patients taking other drugs that decrease heart rate, treatment with MAYZENT should generally not be initiated without consultation from a cardiologist because of the potential additive effect on heart rate [see Dosage and Administration (2.4) in the full prescribing information and Drug Interactions (7.2)].

Missed Dose During Treatment Initiation and Reinitiation of Therapy Following Interruption If a titration dose is missed or if 4 or more consecutive daily doses are missed during maintenance treatment, reinitiate Day 1 of the dose titration and follow titration monitoring recommendations [see Dosage and Administration (2.2, 2.3) in the full prescribing information].

5.4 Respiratory Effects Dose-dependent reductions in absolute forced expiratory volume over 1 second (FEV1) were observed in MAYZENT-treated patients as early as 3 months after treatment initiation. In a placebo-controlled trial in adult patients, the decline in absolute FEV1 from baseline compared to placebo was 88 mL [95% confidence interval (CI): 139, 37] at 2 years. The mean difference between MAYZENT-treated patients and patients receiving placebo in percent predicted FEV1 at 2 years was 2.8% (95% CI: -4.5, -1.0). There is insufficient information to determine the reversibility of the decrease in FEV1 after drug discontinuation. In Study 1, five patients discontinued MAYZENT because of decreases in pulmonary function testing. MAYZENT has been tested in MS patients with mild to moderate asthma and chronic obstructive pulmonary disease. The changes in FEV1 were similar in this subgroup compared with the overall population. Spirometric evaluation of respiratory function should be performed during therapy with MAYZENT if clinically indicated.

5.5 Liver Injury Elevations of transaminases may occur in MAYZENT-treated patients.

Recent (i.e., within last 6 months) transaminase and bilirubin levels should be reviewed before initiation of MAYZENT therapy.

In Study 1, elevations in transaminases and bilirubin were observed in 10.1% of MAYZENT-treated patients compared to 3.7% of patients receiving placebo, mainly because of transaminase [alanine aminotransferase/aspartate aminotransferase/gamma-glutamyltransferase (ALT/AST/GGT)] elevations.

In Study 1, ALT or AST increased to three and five times the upper limit of normal (ULN) in 5.6% and 1.4% of MAYZENT-treated patients, respectively, compared to 1.5% and 0.5% of patients receiving placebo, respectively. ALT or AST increased eight and ten times ULN in MAYZENTtreated patients (0.5% and 0.2%, respectively) compared to no patients receiving placebo. The majority of elevations occurred within 6 months of starting treatment. ALT levels returned to normal within approximately 1 month after discontinuation of MAYZENT. In clinical trials, MAYZENT was discontinued if the elevation exceeded a 3-fold increase and the patient showed symptoms related to hepatic dysfunction.

Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice and/or dark urine during treatment, should have liver enzymes checked. MAYZENT should be discontinued if significant liver injury is confirmed.

Although there are no data to establish that patients with preexisting liver disease are at increased risk to develop elevated liver function test values when taking MAYZENT, caution should be exercised when using MAYZENT in patients with a history of significant liver disease.

5.6 Increased Blood Pressure In Study 1, MAYZENT-treated patients had an average increase over placebo of approximately 3 mmHg in systolic pressure and 1.2 mmHg in diastolic pressure, which was first detected after approximately 1 month of treatment initiation and persisted with continued treatment. Hypertension was reported as an adverse reaction in 12.5% of MAYZENT-treated patients and in 9.2% of patients receiving placebo. Blood pressure should be monitored during treatment with MAYZENT and managed appropriately.

5.7 Fetal Risk Based on animal studies, MAYZENT may cause fetal harm [see Use in Specific Populations (8.1)]. Because it takes approximately 10 days to eliminate MAYZENT from the body, women of childbearing potential should use effective contraception to avoid pregnancy during and for 10 days after stopping MAYZENT treatment.

5.8 Posterior Reversible Encephalopathy Syndrome Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a sphingosine 1-phosphate (S1P) receptor modulator. Such events have not been reported for MAYZENT-treated patients in the development program. However, should a MAYZENTtreated patient develop any unexpected neurological or psychiatric symptoms/signs (e.g., cognitive deficits, behavioral changes, cortical

visual disturbances, or any other neurological cortical symptoms/signs), any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration, the physician should promptly schedule a complete physical and neurological examination and should consider a MRI. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, MAYZENT should be discontinued.

5.9 Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or Immune-Modulating Therapies When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation, when initiating MAYZENT. Initiating treatment with MAYZENT after treatment with alemtuzumab is not recommended [see Drug Interactions (7.1)].

5.10 Severe Increase in Disability After Stopping MAYZENT Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping MAYZENT treatment. Patients should be observed for a severe increase in disability upon MAYZENT discontinuation and appropriate treatment should be instituted, as required.

5.11 Immune System Effects After Stopping MAYZENT After stopping MAYZENT therapy, siponimod remains in the blood for up to 10 days. Starting other therapies during this interval will result in concomitant exposure to siponimod.

Lymphocyte counts returned to the normal range in 90% of patients within 10 days of stopping therapy [see Clinical Pharmacology (12.2) in the full prescribing information]. However, residual pharmacodynamics effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3-4 weeks after the last dose. Use of immunosuppressants within this period may lead to an additive effect on the immune system, and therefore caution should be applied 3-4 weeks after the last dose of MAYZENT [see Drug Interactions (7.1)].

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: • Infections [see Warnings and Precautions (5.1)] • Macular Edema [see Warnings and Precautions (5.2)] • Bradyarrhytmia and Atrioventricular (AV) Conduction Delays [see Warnings and Precautions (5.3)] • Respiratory Effects [see Warnings and Precautions (5.4)] • Liver Injury [see Warnings and Precautions (5.5)] • Increased Blood Pressure [see Warnings and Precautions (5.6)] • Fetal Risk [see Warnings and Precautions (5.7)] • Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.8)] • Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or Immune-Modulating Therapies [see Warnings and Precautions (5.9)] • Severe Increase in Disability After Stopping MAYZENT [see Warnings and Precautions (5.10)] • Immune System Effects After Stopping MAYZENT [see Warnings and Precautions (5.11)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 1737 MS patients have received MAYZENT at doses of at least 2 mg daily. These patients were included in Study 1 [see Clinical Studies (14) in the full prescribing information] and in a Phase 2 placebocontrolled study in patients with MS. In Study 1, 67% of MAYZENT-treated patients completed the double-blind part of the study, compared to 59.0% of patients receiving placebo. Adverse events led to discontinuation of treatment in 8.5% of MAYZENT-treated patients, compared to 5.1% of patients receiving placebo. The most common adverse reactions (incidence at least 10%) in MAYZENT-treated patients in Study 1 were headache, hypertension, and transaminase increases.

Table 3 lists adverse reactions that occurred in at least 5% of MAYZENTtreated patients and at a rate at least 1% higher than in patients receiving placebo.

Table 3 Adverse Reactions Reported in Study 1 (Occurring in at Least 5% of MAYZENT-Treated Patients and at a Rate at Least 1% Higher Than in Patients Receiving Placebo) Adverse Reaction Headachea Hypertensionb Transaminase increasedc Falls Edema peripherald Nausea Dizziness Diarrhea Bradycardiae Pain in extremityf

MAYZENT 2 mg (N = 1099) %

Placebo (N = 546) %

15 13 11 11 8 7 7 6 6 6

14 9 3 10 4 4 5 4 3 4

Terms were combined as follows: tension headache, sinus headache, cervicogenic headache, drug withdrawal headache, and procedural headache. bhypertension, blood pressure increased, blood pressure systolic increased, essential hypertension, blood pressure diastolic increased. calanine aminotransferase increased, gamma-glutamyltransferase increased, hepatic enzyme increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, liver function test increased, hepatic function abnormal, liver function test abnormal, transaminases increased. dedema peripheral, joint swelling, fluid retention, swelling face. ebradycardia, sinus bradycardia, heart rate decreased. fpain in extremity and limb discomfort. aheadache,

The following adverse reactions have occurred in less than 5% of MAYZENT-treated patients but at a rate at least 1% higher than in patients receiving placebo: herpes zoster, lymphopenia, seizure, tremor, macular edema, AV block (1st and 2nd degree), asthenia, and pulmonary function test decreased [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)].

Seizures In Study 1, cases of seizures were reported in 1.7% of MAYZENT-treated patients, compared to 0.4% in patients receiving placebo. It is not known whether these events were related to the effects of MS, to MAYZENT, or to a combination of both.

Respiratory Effects Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) were observed in patients treated with MAYZENT [see Warnings and Precautions (5.4)].

Vascular Events Vascular events, including ischemic strokes, pulmonary embolisms, and myocardial infarctions, were reported in 3.0% of MAYZENT-treated patients compared to 2.6% of patients receiving placebo. Some of these events were fatal. Physicians and patients should remain alert for the development of vascular events throughout treatment, even in the absence of previous vascular symptoms. Patients should be informed about the symptoms of cardiac or cerebral ischemia caused by vascular events and the steps to take if they occur.

Malignancies Malignancies such as malignant melanoma in situ and seminoma were reported in MAYZENT-treated patients in Study 1. An increased risk of cutaneous malignancies has been reported in association with another S1P modulator.

7 DRUG INTERACTIONS 7.1 Anti-Neoplastic, Immune-Modulating, or Immunosuppressive Therapies MAYZENT has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during such therapy and in the weeks following administration [see Warnings and Precautions (5.1)].

When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects [see Warnings and Precautions (5.9)].

Because of the characteristics and duration of alemtuzumab immune suppressive effects, initiating treatment with MAYZENT after alemtuzumab is not recommended.

MAYZENT can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.

7.2 Anti-Arrhythmic Drugs, QT Prolonging Drugs, Drugs That May Decrease Heart Rate MAYZENT has not been studied in patients taking QT prolonging drugs.

Class Ia (e.g., quinidine, procainamide) and Class III (e.g., amiodarone, sotalol) anti-arrhythmic drugs have been associated with cases of Torsades de Pointes in patients with bradycardia. If treatment with MAYZENT is considered, advice from a cardiologist should be sought.

Because of the potential additive effects on heart rate, treatment with MAYZENT should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers (e.g., verapamil, diltiazem), or other drugs that may decrease heart rate (e.g., ivabradine, digoxin) [see Warnings and Precautions (5.3) and Drug Interactions (7.3)]. If treatment with MAYZENT is considered, advice from a cardiologist should be sought regarding the switch to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

7.3 Beta-Blockers Caution should be applied when MAYZENT is initiated in patients receiving treatment with a beta-blocker because of the additive effects on lowering heart rate; temporary interruption of the beta-blocker treatment may be needed prior to initiation of MAYZENT [see Warnings and Precautions (5.3)]. Beta-blocker treatment can be initiated in patients receiving stable doses of MAYZENT [see Clinical Pharmacology (12.2) in the full prescribing information].

7.4 Vaccination During and for up to one month after discontinuation of treatment with MAYZENT, vaccinations may be less effective; therefore MAYZENT treatment should be paused 1 week prior and for 4 weeks after vaccination [see Warnings and Precautions (5.1)].

The use of live attenuated vaccines may carry the risk of infection and should therefore be avoided during MAYZENT treatment and for up to 4 weeks after discontinuation of treatment with MAYZENT [see Warnings and Precautions (5.1)].

7.5 CYP2C9 and CYP3A4 Inhibitors Because of a significant increase in exposure to siponimod, concomitant use of MAYZENT and drugs that cause moderate CYP2C9 and moderate or strong CYP3A4 inhibition is not recommended. This concomitant drug regimen can consist of a moderate CYP2C9/CYP3A4 dual inhibitor (e.g., fluconazole) or a moderate CYP2C9 inhibitor in combination with a separate - moderate or strong CYP3A4 inhibitor.

Caution should be exercised for concomitant use of MAYZENT with moderate CYP2C9 inhibitors.

7.6 CYP2C9 and CYP3A4 Inducers Because of a significant decrease in siponimod exposure, concomitant use of MAYZENT and drugs that cause moderate CYP2C9 and strong CYP3A4 induction is not recommended for all patients. This concomitant drug regimen can consist of moderate CYP2C9/strong CYP3A4 dual inducer (e.g., rifampin or carbamazepine) or a moderate CYP2C9 inducer in combination with a separate strong CYP3A4 inducer.

Caution should be exercised for concomitant use of MAYZENT with moderate CYP2C9 inducers.

Concomitant use of MAYZENT and moderate (e.g., modafinil, efavirenz) or strong CYP3A4 inducers is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype [see Clinical Pharmacology (12.3) in the full prescribing information].

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of MAYZENT in pregnant women. Based on animal data and its mechanism of action, MAYZENT can cause fetal harm when administered to a pregnant woman (see Data). Reproductive and developmental studies in pregnant rats and rabbits have demonstrated MAYZENT-induced embryotoxicity and fetotoxicity in rats and rabbits and teratogenicity in rats.

Increased incidences of post-implantation loss and fetal abnormalities (external, urogenital and skeletal) in rat and of embryo-fetal deaths, abortions and fetal variations (skeletal and visceral) in rabbit were observed following prenatal exposure to siponimod starting at a dose 2 times the exposure in humans at the highest recommended dose of 2 mg/day.

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data Animal Data When siponimod (0, 1, 5, or 40 mg/kg) was orally administered to pregnant rats during the period of organogenesis, post implantation loss and fetal malformations (visceral and skeletal) were increased at the lowest

dose tested, the only dose with fetuses available for evaluation.

A no-effect dose for adverse effects on embryo-fetal development in rats was not identified. Plasma exposure AUC at the lowest dose tested was approximately 18 times that in humans at the recommended human dose (RHD) of 2 mg/day.

When siponimod (0, 0.1, 1, or 5 mg/kg) was orally administered to pregnant rabbits during the period of organogenesis, embryolethality and increased incidences of fetal skeletal variations were observed at all but the lowest dose tested. Plasma exposure (AUC) at the no-effect dose (0.1 mg/kg) for adverse effects on embryo-fetal development in rabbits is less that than in humans at the RHD. When siponimod (0, 0.05, 0.15, or 0.5 mg/kg) was orally administered to female rats throughout pregnancy and lactation, increased mortality, decreased body weight, and delayed sexual maturation were observed in the offspring at all but the lowest dose tested. An increase in malformations was observed at all doses. A no-effect dose for adverse effects on pre- and postnatal development in rats was not identified. The lowest dose tested (0.05 mg/kg) is less than the RHD, on a mg/m2 basis.

8.2 Lactation Risk Summary There are no data on the presence of siponimod in human milk, the effects of MAYZENT on the breastfed infant, or the effects of the drug on milk production. A study in lactating rats has shown excretion of siponimod and/or its metabolites in milk. The developmental and health benefits of breastfeeding should be considered along with the motherâ&#x20AC;&#x2122;s clinical need for MAYZENT and any potential adverse effects on the breastfed infant from MAYZENT or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential Contraception Females Before initiation of MAYZENT treatment, women of childbearing potential should be counselled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with MAYZENT [see Use in Specific Populations (8.1)]. Since it takes approximately 10 days to eliminate the compound from the body after stopping treatment, the potential risk to the fetus may persist and women should use effective contraception during this period [see Warnings and Precautions (5.7)].

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use Clinical studies of MAYZENT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 CYP2C9 Genotype Before initiation of treatment with MAYZENT, test patients to determine CYP2C9 genotype. MAYZENT is contraindicated in patients homozygous for CYP2C9*3 (i.e., CYP2C9*3/*3 genotype), which is approximately 0.4%-0.5% of Caucasians and less in others, because of substantially elevated siponimod plasma levels. MAYZENT dosage adjustment is recommended in patients with CYP2C9*1/*3 or *2/*3 genotype because of an increase in exposure to siponimod [see Dosage and Administration (2.3) and Clinical Pharmacology (12.5) in the full prescribing information].

10 OVERDOSAGE In patients with overdosage of MAYZENT, it is important to observe for signs and symptoms of bradycardia, which may include overnight monitoring. Regular measurements of pulse rate and blood pressure are required, and ECGs should be performed [see Warnings and Precautions (5.3, 5.6) and Clinical Pharmacology (12.2) in the full prescribing information].

There is no specific antidote to siponimod available. Neither dialysis nor plasma exchange would result in meaningful removal of siponimod from the body. The decrease in heart rate induced by MAYZENT can be reversed by atropine or isoprenaline.

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 MAYZENT is a registered trademark of Novartis AG Š Novartis T2019-45

Tools & Resources

Promoting Team-based Care: New Patient Scheduling Method

By Calli Cook, DNP, APRN, FNP-C, Chair of the AAN Consortium of Neurology APPs Advanced practice providers (APPs) are an integral part of the neurology care team. However, many APPs are trained as generalists and need on-the-job training to be efficient and effective members of the neurology care team. In addition to formal orientation and onboarding, there are scheduling methods that can be used to improve novice neurology APPs’ learning that do not limit the productivity of the precepting neurologist or APP. One successful scheduling method includes the novice APP working from the preceptor’s schedule that is double-booked.

For instance, the preceptor would have two patients scheduled within an hour slot (see below). One patient would be a follow-up and the other would be a new consult. The novice neurology APP would begin seeing the new patient while the preceptor would address the follow-up visit. After completing the follow-up visit, the preceptor would discuss the new patient with the APP. 1:00 p.m. Return Patient Visit—preceptor

New Patient Visit—APP 2:00 p.m. Return Patient Visit—preceptor

New Patient Visit—APP The APP would present the patient to the preceptor with a tiered differential diagnosis and treatment plan. The preceptor/ APP team would discuss the diagnosis and plan, returning to the patient together and presenting the agreed upon plan to the EXEC: 20 Transitioning Page Horizontal> patient andCEO/Thankyou addressing Ad—Half any questions the noviceAN APP might have.

Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C

The method allows the APP to benefit from Cook active learning instead of passively learning through shadowing the preceptor. This also creates a positive image of the neurology team for the patient and increases patient security in seeing the APP as the patient is better able to understand how the team works together to provide care.

This scheduling method can improve professional development through continued learning and may lead to improved APP role satisfaction. By working to enhance APP role satisfaction, retention can be improved. Team-based care is essential to ensuring patients receive best care and APPs are practicing at the full scope of practice. The model achieves both targets without drastically affecting overall productivity.

The AAN is dedicated to providing education, tools, and resources that promote team-based care and support the integral role APPs play in a neurology practice. For more information, visit AAN.com/tools-and-resources/advanced-practice-providers or email practice @aan.com. 

Thank you, Cathy, for your 21 years of exemplary leadership and service to the Academy.

Best wishes for your retirement! ~ Your AAN Staff

Policy & Guidelines

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New Guideline Evaluates Treatments for Sleep Challenges in Children with Autism The AAN published the guideline “Treatment for Insomnia and Disrupted Sleep Behavior in Children and Adolescents with Autism Spectrum Disorder” in the February 12, 2020, online issue of Neurology ® and the March 3, 2020, print issue.

The guideline states there are many factors that may contribute to sleep challenges in children and adolescents. These include medicines, other health conditions, emotional disorders, and family and social factors. Children and adolescents with autism spectrum disorder may be especially at risk for sleep problems caused by these contributing factors. If a child has autism spectrum disorder and sleep problems, a knowledgeable clinician should do a thorough evaluation to find the cause(s) of the sleep problems.

Caregivers should be aware that their child’s sleep problems may not be “caused” by autism spectrum disorder, while understanding that core and associated symptoms of this disorder may add to or worsen a child’s sleep problems.

After other potential treatable causes of the sleep problems have been ruled out, children with autism spectrum disorder may benefit from behavioral treatments for sleep problems, receiving correct amounts of melatonin, or a combination of these approaches.

Read the guidelines and access summaries for clinicians and families/caregivers and a slide presentation set at AAN.com.

For more information, email guidelines@aan.com or call (612) 928-6056. 

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Grants Help Advocates Keep Moving Change Forward Nine AAN members who have graduated from the Palatucci Advocacy Leadership Forum (PALF) have received 2020 PALF Action Grants to keep their projects moving forward. A total of $5,000 was distributed among the individuals to help them complete their action plan and continue their advocacy success. The recipients are required to provide an objective, measurable, and feasible outcome to be accomplished within a specific time frame, and they must include detailed information on how the funds will be allocated and spent.

Antonio Moya, MD / Class of 2018

Philip Tipton, MD / Class of 2018

Creating a stroke awareness video to educate the Los Angeles Filipino American community and assess its efficacy in changing health behaviors and attitudes among Filipino Americans.

The creation of Long Live the Brains Podcast and YouTube channel to increase awareness about neurodegenerative diseases with the ultimate goal of destigmatizing these diseases and stressing the importance of supporting organizations dedicated to funding patient care and disease research.

Megan Selvitelli, MD / Class of 2019 Developing a Maine Neurological Society.

Christian Gericke, MD, PhD, MPH, MSc, MBA / Class of 2019 Advocate to the Australian Government Department of Health to bring the national formulary for antiepileptic drugs (AEDs) in line with international clinical guidelines and make access to AEDs more affordable.

Qurat Khan, MD / Class of 2019 Forming a team of master trainers for dementia in Pakistan for the purpose of improving awareness and capacity building, especially for the caregivers of people with dementia.

Yvette Brown, MD / Class of 2019 In coordination with Native Health, a community health center in the downtown Phoenix area serving urban Native American population, Brown’s project strives to increase the awareness of concussions symptoms and community resources for evaluation and management to high school athletes and parents.

Anna Hohler, MD, FAAN / Class of 2004 Working with first responders to determine the incidence of signs and symptoms of Parkinson’s disease, and provide resources for medical care related to these medical issues.

Kara Stavros, MD / Class of 2018

Justin Martello, MD / Class of 2019 Creating a state-wide plan in Delaware for Parkinson's disease care, including the creation of a website acting as a single repository of information for education, care resources throughout the state, and way of communication between patients, caregivers, and providers.

Growing successful advocacy curriculum for neurology residents at Rhode Island Hospital. 

Apply by March 9 to Participate in 2020 PALF Time is running out to apply for the 18th annual Palatucci Advocacy Leadership Forum. If you have an advocacy project that will improve the lives of neurology patients or strengthen the practice of neurology in your workplace, community, or state, apply by March 9.

This popular advocacy leadership training program will take place July 23–26, 2020, at the Hyatt Tamaya Resort in Albuquerque, NM. Learn more and apply at AAN.com/PALF. 

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Policy & Guidelines

Capitol Hill Report Capitol Hill Report presents regular updates on legislative and regulatory actions and how the Academy ensures that the voice of neurology is heard on Capitol Hill. It is emailed to US members twice monthly and is posted at AAN.com/view/HillReport. Below are some recent highlights.

AAN Submits Comments in Coordinated Effort to Protect E/M Change On January 28, the AAN submitted comments to the Centers for Medicare & Medicaid Services (CMS) related to finalized provisions of the 2020 Physician Fee Schedule. The comments are part of a coordinated effort with multiple specialty societies to protect positive changes made to the evaluation and management (E/M) codes and to ensure that the positive changes are implemented without modification or delay on January 1, 2021. The AAN has identified two key areas that opponents of the changes are likely to target. These are the complexity add-on code and the decision to exclude those E/M services provided during a surgical global period from the increase. The AAN’s comments include a robust defense of both provisions and the AAN is actively working to promote the benefits of both provisions, as well as the overall benefits of the finalized changes.

Additionally, the AAN is working with coalition partners to coordinate messages and to schedule a meeting with CMS to discuss the need to protect the new E/M coding structure and values. The AAN, along with several other specialty societies, is also conducting targeted outreach on the Hill to ensure that members of Congress are educated on the specific benefits of the finalized E/M changes. E/M remains a top priority for the AAN for 2020. The AAN is working diligently to protect the outcome of the AAN’s multi-year long, award-winning advocacy effort to maximize reimbursement for cognitive services.

AAN Member Testifies to Rhode Island House Commission on Step Therapy Protocols Member Perspective by Jonathan F. Cahill, MD In Rhode Island and around the United States, step therapy protocols are increasingly used as a way for insurance companies to contain costs. Step therapy protocols, by requiring the failure of one drug or more before allowing patients access to the initially prescribed medication, interfere with patient-centered decision making. They are meant to ensure that safe, appropriate, and affordable drugs are provided to patients, but problems arise when step therapy requirements dictate which drugs individuals may access, and when decisions made by patients with their doctors are second-guessed or overturned. One problem is that the definition of failure of one or another drug is not standard, and

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the person determining failure is not always clear (the prescribing physician, the patient, the insurance company).

Additionally, some policies do not consider failures of drugs that occurred when the patient was covered by a prior health insurance plan. This is clearly not in the best interests of patients to require them to restart medications that previously were not effective or to which they were intolerant.

In my experience, step therapy protocols are becoming more prevalent and more restrictive over the past few years. In response, 23 states have enacted legislation to allow for individuals to easily apply for exemptions to step therapy protocols. In Rhode Island, the state legislature was unsuccessful in passing such legislation last year and instead has created a state commission to further study the issue and make recommendations to the legislature. I was fortunate to have the opportunity to testify before the House Committee on Health, Education and Welfare in support of last year’s bill, and I look forward to testifying again before the commission later this month. My testimony includes specific examples of patients whose medications have been denied as part of a step therapy protocol.

Most of my patients live with multiple sclerosis (MS). Since the first drug proven to alter the course of MS was approved by the US Food and Drug Administration (FDA) in 1993, there have been many advances in drug therapy to treat the disease. There are now 17 FDA-approved disease-modifying therapies, and they are giving people with MS more control over the disease and leading to less disability over time. The decision about which medication is right for a specific patient is complicated, and influenced by the individual’s symptoms and disease course, the available testing, patient preferences, other medical issues, potential risk for side effects, and planned duration of treatment. It is essential that Rhode Island and other states, as well as the federal government, protect patient-centered medical decision making by enacting policies to make it easier for patients to seek step therapy protocol exemptions.

Note: The AAN is piloting a state advocacy strategy in 2020 to focus on step therapy, electronic prior authorization, and scope of practice threats in a select group of states. In addition to Dr. Cahill’s testimony, the AAN also submitted a letter to the state commission in support of step therapy reform.

If you are currently engaged in your state on any of these issues, please email advocacy@aan.com. 

American Brain Foundation

Impressive Lineup of Honorees Slated for Commitment to Cures Fundraiser An impressive lineup of honorees will be recognized during the American Brain Foundation’s 2020 Commitment to Cures, set for Wednesday, April 29, at the Hilton Toronto during the AAN Annual Meeting. The popular annual dinner and fundraiser has a long tradition of supporting the Foundation—the AAN’s philanthropic partner—by offering an opportunity for leaders in neurology to honor prestigious members of the public for their contributions to finding cures for brain diseases through advocacy, public awareness, and fundraising. Funds raised from the Commitment to Cures event will support the Foundation’s research mission, which includes providing funds for crucial medical research across the whole spectrum of brain diseases and disorders.

Space and tickets are limited. Visit AmericanBrainFoundation.org/C2C to secure your spot or contact events@americanbrainfoundation.org or (866) 770-7570 for more information.

Emilia Clarke

Sidney Crosby

Catherine M. Rydell, CAE

Jim Cramer

Public Leadership in Neurology Award Recipient

Commitment to Cures Award Recipient

Board Chair Award Recipient

Master of Ceremonies and Ambassador Award Recipient

The Game of Thrones actor will be recognized for her impact in sharing her personal experience with brain aneurysms and surgery, and for founding a charity to propel neurorehabilitation support services for millions of people.

The captain of the Pittsburgh Penguins will be recognized for raising awareness of sports concussion and encouraging changes to reduce traumatic brain injury in ice hockey.

The outgoing chief executive officer of the American Academy of Neurology will be recognized for her 21 years developing and shaping the American Brain Foundation through her leadership and philanthropy.

The host of MSNBC’s Mad Money will be recognized for his tireless advocacy for migraine.

Michael D. Hill, MD; Andrew M. Demchuk, MD; and Mayank Goyal, MD Scientific Breakthrough Award Recipients The team from the Calgary Stroke Program, University of Calgary will be recognized for groundbreaking research in treating acute ischemic stroke.

AANnews • March 2020 33

Education & Research

UCNS Expands Certification Eligibility to Doctors of Osteopathy Physicians who hold a primary certification by the American Osteopathic Association (AOA) are now eligible to apply for UCNS subspecialty certification. The UCNS certification general eligibility criteria for certification has been updated to include doctors of osteopathy (DOs) who have trained at an AOA accredited residency program and are boarded by an AOA Board. The change will go into effect beginning with the 2020 subspecialty certification examinations.

“The AOA-accredited programs are transitioning over to Accreditation Council for Graduate Medical Education due to the new single accreditation system, however, there are many DOs who completed their training prior to this change. The new UCNS general eligibility criteria change now provides an inclusive opportunity for DOs to pursue UCNS certification,” said Matthew E. Fink, MD, FAAN, chair of the UCNS Certification Council.

Fink

Certification eligibility criteria and information for each subspecialty can be found under “Certification” at UCNS.org. 

Visit our booth at the annual meeting in Toronto!

RESEARCH

Learn about research funding opportunities

PHOTOS

Win prizes at our photo booth

TEES

Show your support with an exclusive t-shirt

The American Brain Foundation brings researchers and donors together to cure brain diseases and disorders. For more information, visit AmericanBrainFoundation.org.

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