2021 April AANnews

VOLUME 34 · ISSUE 4 · APRIL 2021

Visit AAN.com/Covid19 for the latest pandemic information and resources to support you and your crucial work.

FAUCI, KOROSHETZ, AND OTHER TOP RESEARCHERS TO PRESENT HOTTEST TOPICS, LATEST ADVANCES Attend Virtual Plenary Sessions From the hottest and timeliest science around COVID-19 and other important clinical topics to controversial issues and a year-end review of top findings, this year’s plenary sessions will feature an impressive lineup of researchers showcasing their very latest breakthroughs in neuroscience. For more information, visit AAN.com/21AM.

April 17– April 22

Hot Topics: Neuro COVID-19 Saturday, April 17, at 5:00 p.m. ET For the first time, the 2021 Hot Topics Plenary Session will focus entirely on one important issue, the global COVID-19 pandemic. Join the keynote address with Walter J. Koroshetz, MD, FAAN, and Anthony S. Fauci, MD, who have been at the forefront of the public health crisis. Four outstanding speakers Continued on page 6

Apply to a Premier AAN Leadership Development Program

The application period for the AAN’s Leadership Development Programs will open this spring. Read about how valuable these programs are to curent participants and visit AAN.com/lead to apply—or recommend one of these transformative opportunities to a qualified and deserving colleague!

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10 Vote on Board Nominees,

Bylaws Change During April 17 Business Meeting

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Fauci

Koroshetz

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President’s Column

Who Says There Is No Such Thing as a Free Lunch?

Greetings to all Academy members and staff! As my term as your president draws to a close, I have had time to reflect on my 30-year journey as a volunteer member of the AAN and what an incredible ride it has been. Like many of you, I was vaguely familiar with the organization as a resident, Stevens receiving the “green journal” for the latest in neurologic research and having the privilege during my training to travel to an AAN Annual Meeting to attend various educational and scientific courses. After my training, I joined a private practice group which encouraged attendance to the Annual Meeting in order to keep up to date

24 Compensation and Productivity Survey Delivers Reliable, Usable Data

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27 New Synapse Community

Fosters Safety and Quality Improvement

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AANnews · April 2021

April Highlights 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

AAN Chief Executive Officer: Mary E. Post, MBA, CAE

Editor-in-Chief: Melissa W. Ko, MD, FAAN, CPE 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.

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Explore Ways to Enhance Your Career, Patient Care, and Wellness at Experiential Learning Areas

Unconventional learning opportunities abound at the following experiential learning areas taking place throughout the virtual 2021 Annual Meeting—and each offering fun and innovative presentations that will employ various teaching and presentation styles.

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Busis, Cascino to Receive President’s Awards During Annual Meeting

Because of the cancellation of last year’s Annual Meeting, two stalwart leaders in neurology will receive the AAN President’s Award during the Presidential Plenary Session at the Annual Meeting. Individuals honored by this award are selected by the AAN president for exemplary services to neurology.

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Business Support Network Launched to Help Business Administrators

It’s not unusual for neurology practice business administrators (BAs) to have questions or need advice about matters that come up during the workday. To help connect them with fellow BAs who might have the answers they seek, the AAN is debuting the Business Support Network.

News Briefs Annual Meeting Abstracts Garner Media Coverage Coverage of the 73rd AAN Annual Meeting is ramping up. An abstract that will be presented at the April meeting about not regaining the senses of taste and smell five months after COVID-19 was covered by Today.com, CNN, and CTV-Canadian Television. Another abstract about exercising two and a half hours a week to prevent migraines was covered by the Daily Mail, US News & World Report, and more than 100 television stations across the country.

New Committee to Drive Patient-Public Projects The AAN Board of Directors recently approved the formation of a new committee, the Patient-Public Initiatives Committee. The committee

will be charged with positioning the AAN and Brain & Life® as the premier organization and brand that own brain health and will advise on and ensure consistent vetting and foster collaboration, coordination, and integration of patient- and public-facing initiatives across the AAN.

Check Out New Resident Lecture Series The AAN has launched a new virtual resident education lecture series to give residents access to subspecialty expertise that may not be currently available at their institution. Each month’s free event will include a speaker and time for Q&A. The one-hour talks are open to all. Contact Allison Perales at aperales@aan.com for more information. 

April 17–April 22

AAN Excellence—Delivered Unconventionally Register now at

AAN.com/21AM

President’s Column

Who Says There Is No Such Thing as a Free Lunch? with the latest thoughts in neurologic care. Our schedules were arranged so half of the group attended the first four days of the conference and the others attended the latter half of the event.

My first meeting as a practicing neurologist occurred in 1991.

It was held at the San Diego Convention Center, an incredibly beautiful but vast expanse of a building to navigate. I recall feeling like a guppy in a sea of humanity, clutching my course schedule and locator map, as I waded through the attendees to make it to my next lecture. I also recall being unable to recognize anyone, feeling oddly isolated in the midst of so many fellow neurologists packing the halls and meeting rooms. Back then, there were no such things as smartphones (very few of us even had cell phones outside of the massive things we kept in our cars), but they did have “message screens” placed throughout the building that would scroll through names alphabetically. Desperately wanting to “connect” with someone at the meeting, I would stare at the screen patiently several times a day, waiting for my letter of the alphabet to appear, but unfortunately, I never saw my name.

Then it happened. As I was making my way from one course to another, and my eyes caught an announcement taped to the wall inviting any member who was recently out of training (less than five years) to a free lunch and discussion that afternoon. That was for me! Still saddled with debt from my student loans, a free lunch was not to be taken lightly, and the possibility of talking to someone besides myself was a bonus.

The meeting was run by Dr. Fran Kittredge, who at the time was chair of the Practice Committee (and later became president of the AAN). He was interested in the opinions of young members about establishing a foundation for funding young investigators in neurology who otherwise would have a very difficult time

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launching their academic careers. This concept evolved over the years to what is now known as the American Brain Foundation.

Well, I must have had so much pent-up energy to converse, I had no problem voicing my thoughts to Dr. Kittredge during the meal.

Afterwards, he approached me and asked if I would be available to share my thoughts with the Practice Committee that evening where dinner would be provided (another free meal and a chance to connect—this was a no-brainer). I am not convinced that my comments were impressive or eloquent during the meeting, but afterwards Dr. Kittredge invited me to serve on one of his subcommittees. I rightly took this as an unbelievable honor and anything that involved neurology, free meals, and conversation had me “all in.” True to his word, I received a letter from him the very next week outlining the subcommittees, giving me the option of choosing which I would be interested in joining.

The subcommittee that caught my eye was called the Quality Standards Subcommittee (QSS), which was based on the concept of performing an extensive review of the literature concerning a clinical topic in our specialty and rating and reporting on the quality of evidence of the published articles. This was a relatively new subcommittee, but I thought it would be a great excuse to review all the relevant literature in clinical neurology so I could be as well-informed as possible. The chair and co-chair of the QSS at the time were Dr. Jay Rosenberg and Dr. Michael Greenberg.

At their next meeting, I was invited to be “interviewed” by them to see if I would be an acceptable addition to their subcommittee.

Although I thought my appointment was a “done deal,” I quickly was informed during the interview that this was not the case.

Fortunately, they decided to take a chance on this private practice neurologist from Indiana and I went on to serve on the QSS for the next 12 years, which were some of the most challenging but rewarding experiences of my career.

After that I was invited to serve on various other subcommittees, work groups, and task

forces, eventually leading to the position as chair of the Practice Committee (the very one that Dr. Kittredge led when I received my free lunch). From there it was on to the Board of Directors, Strategic Planning chair, officer positions, to now.

Fortunately, this organization has become more proactive and sophisticated in engaging and recruiting members into becoming involved through our various leadership programs, Neurology on the Hill, “micro-volunteering” through our email/website requests or through involvement in the various sections and Synapse groups within the Academy.

Over the years, I can certainly attest to the fact that my life has been enriched through all the many brilliant, talented, and caring neurologists, neuroscientists, business managers, advanced practice providers, and staff that I have met along my journey with the AAN. The mentorship, coaching, advice from members I have encountered along the way (you know who you are) has been invaluable and indispensable, but it is the friendships with those I have been able to work most closely I will always treasure.

The opportunity to humbly serve as the president of this great organization has been the honor of a lifetime, notwithstanding its challenges (please attend the Presidential Plenary lecture at the Annual Meeting to hear more). My goal when I started my term was to improve career satisfaction and value for our members and leave the AAN in a better place than when I started. This past year, disruptive events which included the pandemic, social unrest, and political turmoil, not to mention the onboarding of a new CEO and CFO, resulted in many sleepless nights when I wondered if my aspirations were too lofty. I am pleased to report that despite the headwinds we all faced in 2020, the AAN

set records in membership, attendance to our meetings, and is in solid financial shape entering 2021. Recent surveys of our membership yielded results that were incredibly encouraging, including the highest percentage ever recorded of members who found value in their AAN membership and a consistently high percentage of members who would recommend a career in neurology. I can also report with confidence that the AAN will continue to be a vison- and mission-focused organization and will fight for what is important to your career satisfaction. We do listen and will respond.

So, when I contemplate the merits of a “free lunch” and whether it was a reasonable return on investment (ROI) for the AAN, I hope that history will be kind and feel the chicken salad was worth it. I know I have received “in kind” so much more than the two meals in 1991 and will be forever grateful that I decided to say “YES” to an opportunity that was posted on a wall. I would encourage all of you to do the same.

Although circumstances prevent us from meeting face-to-face this year, please feel free to seek me out when we once again can meet in person. I would certainly love and welcome that. So, until that time arrives… Stay safe and stay strong! 

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

AANnews • April 2021 5

Conferences & Community

Fauci, Koroshetz, and Other Top Researchers to Present Hottest Topics, Latest Advances Continued from cover will then summarize their COVID-19-related research findings and describe the clinical implications of their work.

Moderators Natalia S. Rost, MD, MPH, FAAN, FAHA, Boston, MA Paul M. George, MD, PhD, MSE, Stanford, CA Keynote Address: Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and chief medical advisor to President Joe Biden; and Walter Koroshetz, MD, FAAN, director of National Institute of Neurological Disorders and Stroke (NINDS) Biology/Acute Illness of COVID-19 Sherry Chou, MD, MMSc, FNCS, Pittsburgh, PA COVID-19 Disparities: An Urgent Call to Dismantle Structural Racism and Prioritize Justice Nicte I. Mejia, MD, MPH, FAAN, Boston, MA

Frontiers in Neuroscience Saturday, April 17, at 10:00 a.m. ET This plenary session features basic and translational research related to clinical issues of importance. Hear from five outstanding speakers as they summarize their recent research finding and dive into the clinical implications of the results.

Moderator Paul M. George, MD, PhD, MSE, Stanford, CA Organization and Control of Hippocampal Circuits Ivan Soltesz, PhD, Stanford, CA Decoding Speech Cortex Edward Chang, MD, San Francisco, CA Microtubules in Health and Disease Antonina Roll-Mecak, PhD, Bethesda, MD

Tomorrow, and Tomorrow, and Tomorrow: Understanding Neurologic Syndromes Post-Acute COVID-19 Serena Spudich, MD, MA, New Haven, CT

Stem Cell Therapy for Spinal Cord Injury: Transition to the Clinic Mark H. Tuszynski, MD, PhD, FAAN, La Jolla, CA

Vaccine and Immunological Response Igor Koralnik, MD, FAAN, Chicago, IL

Dissecting the Control of Blood Flow Through Brain Capillaries Andy Shih, PhD, Seattle, WA

Presidential Plenary Session Sunday April 18, at 10:00 a.m. ET This session features the AAN’s premier lecture awards for clinically relevant research and a presentation by a leading lecturer. Top researchers speak on some of the most significant findings in neurology in 2021. AAN President James C. Stevens, MD, FAAN, will kick off the session with a presentation of the 2020 President’s Award and Presidential Lecture. After that, tune in for an address from AAN Chief Executive Officer Mary Post, MBA, CAE, followed by a few words from AAN President Elect Orly Avitzur, MD, MBA, FAAN. Session moderators will then introduce this year's list of superb lecturers.

Moderator Natalia S. Rost, MD, MPH, FAAN, FAHA, Boston, MA Presidential Lecture: Disruption: How to Pivot from Uncertainty to Success—The AAN Story James C. Stevens, MD, FAAN, Fort Wayne, IN President, American Academy of Neurology H. Houston Merritt Lecture: Where’s the Vision? The Importance of Visual Outcomes in Neurological Disease Steven Galetta, MD, FAAN, New York, NY Sidney Carter Award in Child Neurology: Gene Therapy Fulfills the Promise for Kids with Neuromuscular Disease Jerry R. Mendell, MD, FAAN, Columbus, OH Robert Wartenberg Lecture: Prevention and Parkinson’s Disease—The Road Forward Caroline Tanner, MD, PhD, FAAN, San Francisco, CA

Contemporary Clinical Issues Plenary Session Monday, April 19, at 10:00 a.m. ET Highlights issues most critical to practicing neurologists, including abstracts related to new therapeutic developments, clinical applications of basic and translational research, and innovative technical developments. The first three topics will be introduced by presenters followed by a commentary from the discussant. The second half of the session will feature standalone talks on various topics.

Moderator Peter Goadsby, MD, PhD, Los Angeles, CA Abstracts Long-term Survival of Participants in the CENTAUR Trials of AMX0035 for ALS Presenter: Sabrina Paganoni, MD, PhD, Boston, MA Discussant: Timothy M. Miller, MD, PhD, St. Louis, MO Neuroimmunology Adverse Events Associated with Immune Checkpoint Inhibitor: A Retrospective, Pharmacovigilance Study Using FAERS Database Presenter: Takahisa Mikami, MD, New York, NY Discussant: Karin Woodman, MD, Houston, TX Prevalence of White Matter Hyperintensities in a Population Aged ≤50 Both with and Without Mild Traumatic Brain Injury Presenter: Teena Shetty, MD, New York, NY Discussant: Jack Tsao, MD, DPhil, FAAN, Bethesda, MD

Invited Speakers Stem Cell Tourism/Regenerative Medicine Sean I. Savitz, MD, Houston, TX

Moderators Martinson K. Arnan, MD, Kalamazoo, MI Amy R. Brooks-Kayal, MD, FAAN, Sacramento, CA

Gene Therapy for Childhood Neuromuscular Syndromes Perry Shieh, MD, PhD, FAAN, Los Angeles, CA

Teleneurology: Can It Replace In-person Visits?

Yes: Tamika M. Burrus, MD, FAAN, Santa Monica, CA No: Amy Guzik, MD, Winston-Salem, NC

Daylights Savings Time: Is There a Controversy?

Phyllis Zee, MD, PhD, Chicago, IL

Clinical Trials Plenary Session Tuesday, April 20, at 10:00 a.m. ET Covers important clinical topics identified from other society meetings that affect patient care. The latest updates within several clinical trials conducted over the course of the last year will be presented.

Moderators Deborah Hall, MD, PhD, FAAN, Chicago, IL Holly E. Hinson, MD, MCR, FAAN, Portland, OR ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) Michael Tymianski, MD, PhD, FRCSC, Toronto, ON, Canada Atogepant Significantly Reduces Mean Monthly Migraine Days in the Phase 3 Trial (ADVANCE) for the Preventive Treatment of Migraine Jessica Ailani, MD, FAAN, McLean, VA Efficacy and Safety of Lower-sodium Oxybate in a Phase 3, Placebo-controlled, Double-blind, Randomized Withdrawal Study in Adult Participants with Idiopathic Hypersomnia Yves Dauvilliers, MD, PhD, Montpellier, France Efficacy, Safety, and Tolerability of Efgartigimod in Patients with Generalized Myasthenia Gravis: Analysis of the Phase 3 ADAPT Study James F. Howard, Jr., MD, FAAN, Chapel Hill, NC Sustained Benefits for 10 kHz Spinal Cord Stimulation Treatment of Painful Diabetic Neuropathy―Six Month Results from a Multicenter Randomized Controlled Trial Erika A. Petersen, MD, FAANS, FACS, Little Rock, AR

Shattering the Clock: Should There Be a Time Window for Acute Stroke Intervention?

Yes: Maarten G. Lansberg, MD, Stanford, CA No: Jeffrey L. Saver, MD, FAAN, Los Angeles, CA Should Amyloid Continue to Be Targeted in Alzheimer’s?

Yes: Jeffrey Cummings, MD, FAAN, Las Vegas, NV No: Mary Sano, PhD, New York, NY

Neurology Year in Review Plenary Session Thursday, April 22, at 10:00 a.m. ET This session looks back at the past year of research, highlighting some of the most relevant strides made in neurology subspecialties, including movement disorders, stroke, and headache. One speaker will examine a topic of particular interest that will examine how we diversify the neurology workforce.

Moderator Fernando Testai, MD, PhD, Chicago, IL Epilepsy Seizure Detection and Device Intervention Kathryn A. Davis, MD, Philadelphia, PA Diversification of the Neurology Workforce Bruce Ovbiagele, MD, MSc, FAAN, San Francisco, CA Therapeutics in Movement Disorders Irene Malaty, MD, FAAN, Gainesville, FL Emerging Therapies for Pediatric Metabolic Disorders Marc C. Patterson, MD, FAAN, FRACP, Rochester, MN Stroke Recovery Heidi M. Schambra, MD, New York, NY Headache Rashmi Halker-Singh, MD, FAAN, Scottsdale, AZ 

Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease Raúl Martínez-Fernández, MD, PhD, Madrid, Spain Efficacy and Safety Results of the Avalglucosidase Alfa Phase 3 COMET Trial in Late-onset Pompe Disease Patients Hani Kushnaf, MD, FAAN, Cincinnati, OH

Controversies in Neurology Plenary Session Wednesday, April 21, at 10:00 a.m. ET This session features experts discussing the most current and controversial issues in neuroscience. Tune in for a scholarly debate between two expert speakers, each advocating for one side of a single topic followed by a rebuttal.

April 17– April 22

AANnews • April 2021 7

#NeurologyProud and proud to call the AAN my home.

Share why you are #NeurologyProud on social media.

Christina Kelly Vest, NP

Conferences & Community

Experience the Annual Meeting Your Way with Curated Interest-based Program Tracks Don’t miss these specially curated course lineups, designed to help you experience the meeting your way and maximize your time with consecutive programming intended to meet your individual career stage, path, and needs.

Academic Medicine Track

COVID-19 Track

Additional Tracks

Designed to help academic neurologists in early career and development or looking to launch into private practice or academics.

This track has been curated to highlight courses that will discuss implications in neurologic care for past or current patients that have been diagnosed with COVID-19.

In addition to formal tracks, we have curated program suggestions for the following groups based on their unique needs:.

Advanced Practice Provider Track Created for cutting-edge advanced practice providers who are new to neurology.

Business of Neurology Track Perfect for private practitioners and business administrators interested in starting a new practice or learning the fundamentals of neurology business.

Career Essentials Track Offering medical students and residents help with early career and development and/or help launching into private practice or academics.

Academic Business Administrators April 18

Futures in Neurological Research Track

Designed to help business administrators take their departments to the next level and get ready to face unique challenges and opportunities. This day-long set of programs will cover a variety of topics including service lines, faculty compensation plans, and more.

This track offers both formal coursework and learning sessions to round out research-interested trainees’ Annual Meeting experience.

Neurohospitalist Track Created specifically for neurohospitalists whose primary focus is inpatient care.

Academic Coordinators Programming specifically designed for residency, fellowship, and clerkship coordinators.

Spanish-language Track Look for education courses, scientific updates, and experiential learning area talks on a wide range of topics taught in Spanish.

For more information, visit AAN.com/21AM. .

Videos Examine Members’ Work on Post-COVID Health and Cultural Issues The inspirational Member Spotlight video series continues with AAN President James C. Stevens, MD, FAAN, interviewing two members who live the values of the AAN in inspiring ways.

Igor J. Koralnik, MD, FAAN, is professor of neurology and section chief of neuro-infectious diseases and global neurology at Northwestern Memorial Hospital in Chicago. He is the founder and director the Neuro COVID-19 Clinic at the hospital, one of the few post-COVID-19 centers to focus solely on the neurologic consequences of the disease. Readers of the November 2020 Neurology Today ® may recall Koralnik featured in the article “Hundreds of ‘Long Haulers’ Present with Neurologic Complaints at Post-COVID-19 Clinics.”

Brain & Life® article “How Physicians and Patients Can Bridge Cultural Divides.”

These interviews and previous videos that show how members are demonstrating AAN values can be seen in a playlist on the AAN YouTube channel at YouTube.com/AANchannel. 

Stevens also spoke with Alyx B. Porter, MD, a neurologist with subspecialty certification in neuro-oncology. Porter, who is a graduate of the AAN Diversity Leadership Program, also directs a cultural humility course at the Mayo Clinic School of Medicine in Phoenix. Porter is part of the faculty for the Communication in Healthcare course for other physicians at the school. Porter’s efforts received attention in the recent

AANnews • April 2021 9

Conferences & Community

Vote on Board Nominees, Bylaws Change During April 17 Virtual Business Meeting AAN members are urged to vote on the slate of nominees for AAN officer and director positions for the 2021–2023 term during the AAN’s 2021 Business Meeting to be held virtually on Saturday, April 17, from 4:00 p.m. to 5:00 p.m. ET during the Annual Meeting.

The meeting will include reports from officers on the accomplishments of the AAN during 2020 and a review of the organizations’ fiscal health.

The classes of membership entitled to vote on any matter during any business meeting of the Academy are Fellow and Neurologist members, and Honorary and Senior members who had voting privileges in their most recent previous category of membership.

Officers President Elect Carlayne E. Jackson, MD, FAAN

Vice President Janis M. Miyasaki, MD, MEd, FRCPC, FAAN

Secretary Sarah M. Benish, MD, FAAN

Treasurer Charles C. Flippen II, MD, FAAN

Directors

Wayne E. Anderson, DO, FAHS, FAAN Brenda Banwell, MD, FAAN Charlene Gamaldo, MD, FAAN, FAASM James N. Goldenberg, MD, CPI, FAPCR, FAAN Larry B. Goldstein, MD, FAHA, FAAN Lily Jung Henson, MD, MMM, FAAN Shannon M. Kilgore, MD, FAAN Brett M. Kissela, MD, MS, FAHA, FAAN Bruce Ovbiagele, MD, MSc, MAS, MBA, FAAN

The current President Elect, Orly Avitzur, MD, MBA, FAAN, will begin her term as President on April 23, 2021. The current President, James C. Stevens, MD, FAAN,

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AANnews • April 2021

will then serve on the Board of Directors as Immediate Past President. The following additional directors will serve as ex officio directors beginning on April 23: Bruce H. Cohen, MD, FAAN, Chair, Advocacy Committee (ex officio) Brad C. Klein, MD, MBA, FAAN, Chair, Medical Economics and Practice Committee (ex officio) José G. Merino, MD, MPhil, FAHA, FAAN, Editor-in-Chief of Neurology® (ex officio) Maisha T. Robinson, MD, MSHPM, FAAN, Chair, Member Engagement Committee (ex officio) Mary E. Post, MBA, CAE, Chief Executive Officer (ex officio, non-voting) The Academy is comprised of two legal entities, the AAN and the AAN Institute.

Most of the elected members of the AAN Board of Directors also serve ex officio on the Board of Directors of the AAN Institute, which includes an independent secretarytreasurer and additional members who serve in ex officio capacities. The AAN Institute Board of Directors will include the following additional members: Jonathan P. Hosey, MD, FAAN, AAN Institute Secretary-Treasurer Lyell K. Jones, Jr., MD, FAAN, Chair, Quality Committee (ex officio) Natalia S. Rost, MD, MPH, FAHA, FAAN, Chair, Science Committee (ex officio) Joseph I. Sirven, MD, FAAN, Chair, Education Committee (ex officio) There also will be consideration of amendments to Article VI, Section 2B of the AAN Bylaws relating to the term for the Editor-in-Chief of Neurology as follows:

B. The Board of Directors shall appoint the Editor-in-Chief, who shall have responsibility for all the contents of the journal NEUROLOGY and oversee the activities of the Editorial Board. The Editor-in-Chief will serve one fivesix-year term, which is renewable for another five- four-year term, unless otherwise approved by the Board of Directors.

The proposed amendment would follow the industry standard for academic medical journals, which is a term increment of five years, renewable for another five years. The proposed amendment would also allow the Board of Directors to make an exception to the term length and increments, if necessary, in order to align the end of the term with the academic year. The AAN Bylaws may be amended at the Business Meeting by the vote of at least two-thirds of the voting members present and voting.

For more information, contact Karen Kasmirski at kkasmirski@aan.com. 

April 17– April 22

Health Care Equity Symposium Debuts The AAN is firmly committed to embracing the diversity of our members, staff, organization, profession, and, ultimately, the patient communities we serve. To this end, the Academy will host its first Health Care Equity Symposium on Monday, April 19 from 1:00 p.m.–3:00 p.m. ET during the upcoming virtual 2021 Annual Meeting. The program will include the Cheryl A. Jay Keynote Lecture by Vice President and Chief Equity and Inclusion Officer at Massachusetts General Hospital Joseph R. Betancourt, MD, MPH, on how to recognize disparities in care and help move towards health equity in neurology. Betancourt’s talk will be followed by an interactive panel discussion on how to recognize disparities in care and how to work towards Inclusion, Diversity, Equity, Anti-racism, and Social Justice (IDEAS) in neurology practice and patient care. The discussion will conclude with a live Q&A with attendees.

Cheryl A. Jay Keynote Lecture Joseph R. Betancourt, MD, MPH Lecture: Structural Equity: Lessons from 2020 Vice president and chief equity and inclusion officer and founder, senior advisor, and faculty of the Disparities Solutions Center (DSC), Massachusetts General Hospital

Panel Members Richard T. Benson, MD, PhD National Institute of Neurological Disorders and Stroke, National Institutes of Health; Director, Office of Global Health and Health Disparities

Nicole Rosendale, MD Assistant Professor of Neurology, University of California, San Francisco

Nicte I. Mejia, MD, MPH, FAAN Assistant Professor of Neurology, Harvard Medical School and Massachusetts General Hospital

Jeffrey C. McClean II, MD, FAAN Lt. Col., United States Air Force, MC deputy chief, Brooke Army Medical Center Department of Medicine For more information, visit AAN.com/21AM .

Inclusion Diversity Equity Anti-racism Social Justice

AANnews • April 2021 11

Conferences & Community

Explore Ways to Enhance Your Career, Patient Care, and Wellness at Experiential Learning Areas Unconventional learning opportunities abound at the following experiential learning areas taking place throughout the virtual 2021 Annual Meeting—and each offering fun and innovative presentations that will employ various teaching and presentation styles.

For a full experiential learning area schedule, visit AAN.com/21AM.

Live Well Learn about self-improvement and resiliency, worklife balance and satisfaction, and how to enhance both personal and professional well-being.

Family Caring and Parenting Sunday, April 18, from 9:00 a.m.–9:20 a.m. ET Amtul Farheen, MD, FAAN We all know that being physicians and caring for your family can be challenging. Let's open up the talk about unique challenges neurologists face while being parents or caring for families. The discussion attempts to promote healthy personal relationships, wellness for parents, and art of worklife balance through a discussion.

Wellness Tips for the Busy Neurologist Saturday, April 17, from 5:00 p.m.–5:20 p.m. ET Rochelle I. Frank, MD This talk will emphasize approaches to maintaining wellness that can be accomplished in a brief time and during a busy day. These will include general approaches and specific accessible activities from multiple different areas impacting physical, mental, spiritual, and emotional well-being. The purpose is to immediately apply these tools in everyday practice.

Enhancing Personal and Professional Well-being Through Appreciative Inquiry Tuesday, April 20, from 9:00 a.m.–9:20 a.m. ET Jeffrey Dewey, MD People and organizations tend to be problem oriented by default, which can lead to negativity and contribute to burnout.

However, in every situation, no matter how negative, there is something that works. Appreciative Inquiry is a method of identifying the core strengths that give life to an individual or organization. While the very act of doing so increases positivity, further impactful change can come from leveraging these strengths to move toward the individual/group's positive potential. This talk will review the basic principles of Appreciative Inquiry and provide practical strategies for applying this methodology.

Zoom Fatigue Saturday, April 17, from 1:00 p.m.–1:20 p.m. ET Belinda A. Savage-Edwards, MD, FAAN This program will explore the psychological and neuropathophysiology of this increasingly prevalent and

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AANnews • April 2021

completely new fatigue referred to as Zoom fatigue. Research based tips will be offered on making virtual communication less exhaustive, thereby reducing the mental and physical toll that come with it.

Cognitive Load and Self Compassion Wednesday, April 21, from 3:00 p.m.–3:20 p.m. ET Amy Grinberg, PhD As providers, we often struggle with treating ourselves with the same level of compassion that we provide to our patients.

What if you could learn to relate to yourself with kindness?

This talk will focus on key tips and techniques for practicing self-compassion in your everyday life.

Careers in Neurology Take part in various talks and networking sessions to help you explore, navigate, and advance your career— no matter what stage you’re in.

What Should Applicants Look for in a Program?

Saturday, April 17, from 1:00 p.m.–1:30 p.m. ET Peter Hannon, MD, and Adam De Havenon, MD This presentation is for medical students and residents to better understand what they should be considering when applying for residency and fellowship. Drawing on years of program director experience in neurology residency and fellowship, the presenters' focus will be on what makes a training program the right fit for an applicant, and not the other way around.

Are You My Mentor?: How to Select a Good Mentor for Your Research Program Sunday, April 18, from 9:00 a.m.–9:30 a.m. ET Deborah Hall, MD, PhD, FAAN Come to this session to learn how to select a good mentor for your research.

A Career in General Neurology: Knowing Everything About Everything Monday, April 19, from 9:00 a.m.–9:30 a.m. ET Kirk Roberts, MD, FAAN The practice of general neurology is uniquely challenging, exciting, and rewarding. While maybe not knowing everything about everything, the general neurologist must know a lot about most things: from the back pain a relative asks about to the newest autoimmune antibody. This discussion will focus on the challenges and rewards of general neurology and ask

for audience participation on how to succeed in this field and how to maintain trainee interest in general neurology in this era of ever-increasing subspecialization.

K Is for Career Development Tuesday, April 20, from 9:00 a.m.–9:30 a.m. ET Holly E. Hinson, MD, MCR, FAAN Interested in applying for a K but don't know where to start?

This session will cover the different types of Ks, how a K differs from other Career Development Awards, the sections of the application, and hints to get started. Attendees will also learn what happens once the application is submitted and the basics of study section, as well as a typical timetable for review. Finding and maximizing appropriate mentorship will be stressed, along with tips and tricks to navigate this key area. The session will end with time for attendee questions.

How the Neuroscience of Bias Changed My Career Thursday, April 22, from 9:00 a.m.–9:30 a.m. ET Jose H. Posas, MD, FAAN In this talk, faculty will delve into how they were able to channel anger and outrage at health care disparities they were seeing around them into actionable items on a rising agenda that has helped them help their patients, their community, and their future colleagues. Faculty will discuss some of the things they don't teach in medical school that have a tremendous impact on shaping how a neurologist can shape their career. Faculty will advise budding neurologists and share wisdom from stumbles in their own career path.

NEW! Academic Neurology Engage in a variety of presentations and conversations and access AAN programs and resources designed specifically for everyone at every level of academia.

Celebrate the AAN academic award recipients including the A.B. Baker Award for Lifetime Achievement in Neurologic Education and awards and scholarships for program directors, clerkship directors, consortia, residents, and medical students.

Different Pathways to Becoming a Chair Saturday, April 17, from 4:00 p.m.–4:30 p.m. ET Frances E. Jensen, MD, FAAN; Cathy A. Sila, MD, FAAN; and Robin Brey, MD, FAAN

This panel will discuss essential responsibilities and traits individuals need to address while considering a future as a chair. Topics will include the timing of taking such a leadership position in one's career, advantages of prior leadership roles, and the effect of the position on other individual pursuits such as research or education. We will discuss pathways to success from a variety of prior backgrounds and draw upon personal experiences of the panelists. The intent is to help those who are considering departmental chair positions to examine how their own narrative can be used to support their success.

Turning “Diversity Tax” into Currency in Neurology Sunday, April 18, from 9:00 a.m.–9:30 a.m. ET Roy H. Hamilton, MD, MS, FAAN Medical trainees and faculty who are persons of color, women, LGBTQI, or hail from other groups that are underrepresented in medicine are often called upon disproportionately to help advance the diversity mission of their academic institutions. This additional obligation, sometimes referred to as the “diversity tax,” can take time away from other activities that are considered important for meeting traditional career benchmarks, can have an unintended negative impact on professional development, and can contribute to career dissatisfaction and burnout.

The objectives of this talk are to recognize the burden that diversity tax places on certain populations of practicing neurologists and trainees; discuss strategies for finding the right balance between promoting diversity-related activities and dedicating oneself to traditional career goals; and present practical strategies for translating diversity-related efforts into activities that are considered meritorious for career development in neurology.

Academic Neurology: What Is the AAN Doing to Help Academic Neurology Saturday, April 17, from 9:00 a.m.–9:30 a.m. ET Ralph L. Sacco, MD, MS, FAHA, FAAN We have launched an academic initiative to help bring together many of the resources, products, and programs that help support academic neurologists across their lifespan, as well as build new ones to meet your needs. Building on Continued on page 14

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April 17– April 22 AANnews • April 2021 13

Conferences & Community

Explore Ways to Enhance Your Career, Patient Care, and Wellness at Experiential Learning Areas Continued page 13 our strong foundation of supportive programs for medical students, neurology clerkship directors, residents, residency program directors, fellows, and fellowship directors, we are expanding our reach to new programs for department chairs, division directors, academic clinicians and researchers, APPs, and other members of departments of neurology. Come hear what the AAN is doing for academic neurology and let us know what else we can do to help you.

How to be an Anti-racist Neurology Department Tuesday, April, 20, from 6:00 p.m.–6:30 p.m. ET Ima M. Ebong, MD, and Nimish Mohile, MD, FAAN We will discuss strategies to overturn existing racist structures and policies in academic neurology departments related to key academic missions: education, clinical care and research. Ebong and Mohile will share their experiences as

diversity officers and provide guidance on how departmental members and leaders in various roles can develop antiracist identities in their departmental work. We will provide specific examples of successful initiatives to integrate anti-racism into departmental strategies and missions.

Sharing of Best Practices for Division Chiefs in an Academic Neurology Department Wednesday, April 21, from 9:00 a.m.–9:30 a.m. ET Brenda Banwell, MD, FAAN This program is for new and current neurology division chiefs to learn best practices in an approach where the speakers talk about things that went great and things we would not do again. We will share ideas for divisional leadership, growth, innovation, human resources, and finance. 

Bestselling Author, Adventurer Alison Levine to Give Inspirational Talk at Annual Meeting Alison Levine, the first American Women's Everest Expedition team captain, adjunct faculty member at the Thayer Leader Development Group at West Point, and New York Times bestselling author of On the Edge: Leadership Lessons from Everest and Other Extreme Environments will inspire Annual Meeting attendees between 1:00 p.m. and 2:00 p.m. ET on Tuesday, April 20, with her talk “On the Edge: The Art of High-impact Leadership.”

No one understands the commitment and leadership necessary to achieve extreme results better than Levine. Despite having been born with a life-threatening condition requiring two cardiac surgeries and suffering from Raynaud’s disease, a condition that cuts the blood flow to her fingers and toes in cold temperatures leaving her at extreme risk for frostbite, she has overcome her challenges to become a history-making adventurer, completing the Adventure Grand Slam of climbing the Seven Summits—the highest peak on each continent—skiing to both the North and South Poles, and being honored as one of only a few presenters at the highly prestigious World Economic Forum in Davos alongside world leaders and top CEOs. “At a time when we are faced with incredible challenges that are beyond our control, we could all use some

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AANnews • April 2021

inspiration,” said Carlayne E. Jackson, MD, FAAN, chair of Meeting Management Committee. “Dealing with the COVID-19 pandemic can in many ways seem similar to Alison Levine's experience climbing Mount Everest and we can learn a lot about how to cope with adversity from the leadership principles she will share.”

Levine’s live 45-minute inspirational talk will focus on the importance of teamwork, determination, tenacity, and the ability to adapt to changing environments as the critical keys to success in all facets of one’s life and career—from Wall Street to the mountain. She will draw on her experience as team captain to make a compelling case that the leadership principles that apply in the world of extreme adventure also apply to today’s rigorously competitive work environments. “Imagine yourself on the highest mountain in the world,” she

Levine

Jackson

explains her best-selling book. “You have to deal with the physiological effects of extreme altitude—along with bonechilling temperatures, battering winds, and a climbing team that's counting on all of its members to make smart decisions. There's simply no room for poor judgment—one mistake or misstep can result in an ‘unrecoverable error.’ In any situation where lives on are the line or the stakes are exceptionally high—there’s no better training ground for leaders than settings where people are pushed beyond their perceived limits.”

Levine’s live talk will be followed by a 15-minute Q&A session.

To learn more, visit AAN.com/21AM. 

Busis, Cascino to Receive President’s Awards During Annual Meeting Because of the cancellation of last year’s Annual Meeting, two stalwart leaders in neurology will receive the AAN President’s Award during the Presidential Plenary Session at the Annual Meeting on Sunday, April 18. Individuals honored by this award are selected by the AAN president for exemplary services to neurology. Both recipients are being honored by AAN President James C. Stevens, MD, FAAN. “It gives me immense personal pleasure to announce the recipient of the 2021 President’s Award, Dr. Neil Busis,” Stevens said. “Dr. Busis has served the AAN in a variety of roles over his greater than 25-year involvement with the organization. He has served on numerous committees, Busis subcommittees, task forces, and work groups, most notably as chair of the Medical Economics and Management Committee, vice chair of our Health Policy Subcommittee, member of the AAN Wellness Joint Coordinating Council, as an advisor to the AMA CPT group, and has served several terms on the AAN Board of Directors. He has given untold number of lectures, webinars, and podcasts concerning practice issues involving coding and billing, telehealth, electronic health records, and physician wellness and burnout.

He is a clinical professor of neurology at both the University of Pittsburgh Medical Center and the New York University Grossman School of Medicine. He has served nationally as a past-president of the American Academy of Electrodiagnostic Medicine and as a member of the National Academy of Medicine writing group for the consensus statement concerning physician burnout and well-being. He has served as an educator in both the private practice setting and in his current position within an academic center. He has long been recognized as the AAN content expert on coding and billing, in electrodiagnostic medicine, telehealth, electronic health records, and physician well-being. A true tour de force of accomplishments reflecting his love and dedication to our profession and to our organization.

Congratulations, Dr. Busis!”

Busis responded to the award, saying, “Thank you very much for this wonderful and totally unexpected honor. I am only one of thousands of volunteers who have contributed to the American Academy of Neurology since its founding. Supporting practice, research, education to enhance the care of patients with neurologic disorders has been our guiding principle. When I joined the AAN as a resident in 1982, there were only about 7,300 members. Today there are more than 36,000. The current breadth, depth, and creativity of the Academy’s activities is responsible for that increase in membership. The advances reflected in today’s programs would inspire awe in a member in 1982. We have found our collective voice with legislators and regulators in Washington, DC, state houses, and with private payers. We have supported ground-breaking research, including studies which assist evidence-based policy and advocacy. Our innovative educational offerings have improved how we teach and how we learn. We promote work-life integration and member well-being. Like many others, I found professional and personal

fulfillment through my service to the Academy and engagement with my colleagues. Over time, these relationships developed into a community that I consider my ‘AAN family.’ To the extent I helped make a difference for our patients and our specialty, I consider myself fortunate to be in the right place at the right time. Past success is prologue to future success. As long as the AAN works to be indispensable to its members—which is the best statement of purpose of any organization I know—the AAN’s future is bright.”

Cascino

Gregory D. Cascino, MD, FAAN, of the Mayo Clinic, who was named recipient of the 2020 AAN President’s Award, also will be recognized during this year’s Presidential Plenary Session. Cascino was chosen by Stevens last year because of his leadership as chair of the Member Engagement Committee and the Academy’s success in attaining a record number of members.

“It is my great pleasure to announce Dr. Greg Cascino as the 2020 recipient of the AAN President’s Award,” said Stevens in a statement last year. “A renowned epileptologist from the Mayo Clinic, Dr. Cascino has admirably served the AAN in various capacities over the past two decades. Known for his boundless energy and enthusiasm, he has been one of our organization’s most effective ambassadors during his many trips abroad as an invited speaker. He has served as the inaugural chair of our Membership Engagement Committee; his visionary leadership has resulted in the exponential growth and retention of our membership that has become the envy of all non-profit medical societies. He has served as a dedicated long-time associate editor of our premier journal Neurology, extending his term well beyond expectations. The AAN will be forever indebted for the selfless, tireless service we have received from Dr. Cascino, a neurologist so deserving of this recognition.”

Cascino responded, “I am honored and delighted to be named the recipient of the 2020 President’s Award. Serving the needs of our AAN members has been a tremendous and unique privilege in my professional career. I would like to thank the many AAN staff and my ‘teammates’ on the Member Engagement Committee and the Board of Directors who have made this an enduring and gratifying experience.” 

April 17– April 22

Conferences & Community

Apply to a Premier AAN Leadership Development Program

Continued from cover

Reflections From 2020–2021 Leadership Program Participants Prior to joining the Diversity Leadership Program, I was focused on how to build a career to be successful in academia. Within our first few sessions, I have learned to reframe my career into one in which academia supports me to achieve my goals. A small reframe, but with powerful implications.” ―Mark Terrelonge, Jr., MD, MPH

The Emerging Leaders Program has been valuable to my growth as a leader. Personality analysis and interactions with other program participants have been insightful about blind spots, and these sessions have been extremely helpful in understanding that differing opinions are essential to meaningful functioning of a team and leader. “ —Muhib Khan, MD

The Transforming Leaders Program has been truly empowering. It has given me personal insights, tools, and language to grow into a more adaptable leader in all aspects of my career. And, through a framework of collegial support, coaching, and mentorship, has offered access to invaluable resources that have strengthened my relationship with the AAN and the neurology community.” ―Mariza Daras, MD

Leadership is a choice. Anybody (including an introvert like me!) can be a leader. The Women Leading in Neurology Program has reminded me to strive to communicate better, stay true to my value, and not be afraid of conflicts. I am now more equipped to explore the root of a conflict and consider conflict an opportunity to communicate and align with others.”

—Michiko Bruno, MD

The Practice Leadership Program has helped me to communicate more effectively. This has been instrumental in my everyday role as a clinical leader. The program has allowed me to appreciate and maximize my strengths, while also being more aware of leadership skills that need improvement."

—Reena Ghode, MD

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Congratulations New Fellows of the American Academy of Neurology!

The AAN congratulates the following members who were named prestigious Fellows of the American Academy of Neurology (FAAN) between December 2020 and February 2021.

Aiesha Ahmed, MD, FAAN Sarwer Al-Bajalan, MD, FAAN Shruti Badhwar-Parasher, DO, FAAN Devin L. Brown, MD, FAAN Katharina M. Busl, MD, MS, FAAN Joel T. Callahan, MD, FAAN Chad Carlson, MD, FAAN Tamara Castillo-Trivino, MD, MAS, FAAN Fernando Cendes, MD, PhD, FAAN Timothy J. Counihan, MD, FAAN Jeremy K. Cutsforth-Gregory, MD, FAAN Rachel Darken, MD, PhD, FAAN David H. Dennison, MD, FAAN Paula Dore-Duffy, PhD, FAAN Mohammed A. El-Sherif, MD, FAAN Anteneh Mekonnen Feyissa, MD, FAAN Partha S. Ghosh, MD, FAAN Corey Goldsmith, MD, FAAN Mark A. Goldstein, MD, FAAN Tanya Harlow, MD, FAAN Mark I. Harris, MD, FAAN Jaime Hatcher-Martin, MD, PhD, FAAN Amy Hellman, MD, FAAN Carrie Michelle Hersh, DO, MSc, FAAN Ahmet Hoke, MD, PhD, FAAN Le Hua, MD, FAAN Milos D. Ikonomovic, MD, FAAN

Yahia Zakaria Bashier Imam, MD, FAAN H.A. Jinnah, MD, PhD, FAAN Karin G. Johnson, MD, FAAN Christopher J. Kenney, MD, FAAN Sanjeev Kumar, MD, FAAN Alan H. Kurland, MD, FAAN Richard Libman, MD, FAAN Naomi Lin, MD, FAAN Angela Lu, MD, FAAN Ana-Claire L. Meyer, MD, FAAN Zeyad Morcos, MD, FAAN Mary Angela O'Neal, MD, FAAN Mary Payne, MD, FAAN Troy A. Payne, MD, FAAN Alberto Ramos, MD, FAAN Amy C. Rauchway, DO, FAAN David Roman Renner, MD, FAAN Tania Reyna, MD, FAAN Rodolfo Savica, MD, PhD, FAAN Nikolaos Scarmeas, MD, FAAN Ludy Chen Shih, MD, FAAN Selden E. Spencer, MD, FAAN Roy E. Strowd III, MD, FAAN Samer D. Tabbal, MD, FAAN Courtney Takahashi, MD, FAAN Gaby T. Thai, MD, FAAN Benjamin David Tolchin, MD, FAAN

Bernard M.J. Uitdehaag, MD, PhD, FAAN Tuhin Virmani, MD, PhD, FAAN Peter Warinner, MD, FAAN Andrew James Westwood, MD, FAAN Jay Elliot Yasen, MD, FAAN 

Interested in Elevating Your Membership Status to FAAN? Visit AAN.com/FAAN to see if you’re eligible for the FAAN designation— or encourage a qualifying colleague to apply. Applying for FAAN status is free, acknowledges exemplary work and achievements in the neurosciences, the clinical practice of neurology, or academic/ administrative neurology; helps set you apart both within the Academy and throughout your professional career; and offers eligibility to serve on the AAN Board of Directors. 

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 • April 2021 17

FOR PATIENTS WITH RELAPSING FORMS OF MS

PLAYING WITH FEWER RELAPSES • The efficacy of VUMERITY® (diroximel fumarate) is based upon bioavailability studies in patients with relapsing forms of multiple sclerosis and healthy subjects comparing dimethyl fumarate to VUMERITY1 • In Study 1 and Study 2 pivotal trials, dimethyl fumarate demonstrated a 53% and 44% relative reduction in annualized relapse rate (ARR) vs placebo, respectively (0.172 vs 0.364; P<0.0001), (0.224 vs 0.401; P<0.0001)1

Indication

• Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Monitoring with MRI for signs 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

Important Safety Information

Herpes Zoster and Other Serious Opportunistic Infections • Serious cases of herpes zoster have occurred in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY), including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on VUMERITY for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered • Other serious opportunistic infections have occurred with dimethyl fumarate, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment • Consider withholding VUMERITY treatment in patients with herpes zoster or other serious infections until the infection has resolved

VUMERITY® (diroximel fumarate) 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.

CONTRAINDICATIONS VUMERITY is contraindicated in patients • With known hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY. Reactions may include anaphylaxis and angioedema • Taking dimethyl fumarate

WARNINGS AND PRECAUTIONS Anaphylaxis and Angioedema • VUMERITY can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in patients taking dimethyl fumarate (which has the same active metabolite as VUMERITY) have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue VUMERITY and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema Progressive Multifocal Leukoencephalopathy • Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with dimethyl fumarate (which has the same active metabolite as VUMERITY). 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. A fatal case of PML occurred in a patient who received dimethyl fumarate for 4 years while enrolled in a clinical trial • PML has occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.9 × 10 9/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8×10 9/L persisting for more than 6 months • At the first sign or symptom suggestive of PML, withhold VUMERITY and perform an appropriate diagnostic evaluation.

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

© 2020 Biogen. All rights reserved. 09/20 VUM-US-0458 v2

Lymphopenia • VUMERITY may decrease lymphocyte counts. In the MS placebo-controlled trials with dimethyl fumarate (which has the same active metabolite as VUMERITY), mean lymphocyte counts decreased by approximately 30% during the first year of treatment with dimethyl fumarate and then remained stable.

Four weeks after stopping dimethyl fumarate, mean lymphocyte counts increased but did not return to baseline. The incidence of infections and serious infections was similar in patients treated with dimethyl fumarate or placebo. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8 x 109/L or ≤0.5 x 10 9/L in controlled trials, although one patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5 x 109/L for 3.5 years) • In controlled and uncontrolled clinical trials with dimethyl fumarate, 2% of patients experienced lymphocyte counts <0.5 x 10 9/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5 x 109/L with continued therapy. Neither VUMERITY nor dimethyl fumarate have been studied in patients with preexisting low lymphocyte counts

Full access to Biogen Support Services • Helping patients start treatment, manage common side effects, and navigate financial assistance

Learn more about additional studies on VUMERITY in RRMS patients2,3

Visit www.vumerityhcp.com

RRMS=relapsing-remitting multiple sclerosis.

• Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with VUMERITY, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of VUMERITY in patients with lymphocyte counts less than 0.5 x 10 9/L persisting for more than six months. Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if VUMERITY is discontinued or interrupted because of lymphopenia. Consider withholding treatment from patients with serious infections until resolution Liver Injury

• Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY) in the postmarketing setting.

The onset has ranged from a few days to several months after initiation of treatment with dimethyl fumarate. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed. These abnormalities resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients • Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials with dimethyl fumarate • Obtain serum aminotransferase, alkaline phosphatase (ALP), and total bilirubin levels prior to treatment with VUMERITY and during treatment as clinically indicated. Discontinue VUMERITY if clinically significant liver injury induced by VUMERITY is suspected Flushing

• VUMERITY may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). In clinical trials of dimethyl fumarate (which has the same active metabolite as VUMERITY), 40% of dimethyl fumarate-treated patients experienced flushing.

Flushing symptoms generally began soon after initiating dimethyl fumarate and usually improved or resolved over time.

In the majority of patients who experienced flushing, it was mild or moderate in severity. Three percent (3%) of patients discontinued dimethyl fumarate for flushing and <1% had serious flushing symptoms that were not life-threatening but led to hospitalization

ADVERSE REACTIONS • The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for dimethyl fumarate (which has the same active metabolite as VUMERITY) were flushing, abdominal pain, diarrhea, and nausea • Gastrointestinal adverse reactions: Dimethyl fumarate caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with dimethyl fumarate compared with placebo. Four percent (4%) of patients treated with dimethyl fumarate and less than 1% of placebo patients discontinued due to gastrointestinal events. The incidence of serious GI events was 1% in patients treated with dimethyl fumarate • Hepatic transaminases: An increased incidence of elevations of hepatic transaminases in patients treated with dimethyl fumarate was seen primarily during the first six months of treatment and most patients with elevations had levels <3 times the upper limit of normal (ULN) during controlled trials. There were no elevations in transaminases ≥ 3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN. Discontinuations due to elevated hepatic transaminases were <1% and were similar in patients treated with dimethyl fumarate or placebo • Eosinophilia adverse reactions: A transient increase in mean eosinophil counts was seen during the first 2 months of therapy

USE IN SPECIFIC POPULATIONS Renal Impairment • No dosage adjustment is necessary in patients with mild renal impairment. Because of an increase in the exposure of a major metabolite, use of VUMERITY is not recommended in patients with moderate or severe renal impairment Please see following pages for Brief Summary of full Prescribing Information.

Study Designs • Study 1: A 2-year, randomized, double-blind, placebo-controlled study in 1234 patients with RRMS. Secondary endpoint: ARR. • Study 2: A 2-year, multicenter, randomized, double-blind, placebo-controlled study in 1417 patients with RRMS. Primary endpoint: ARR. References: 1. VUMERITY Prescribing Information, Biogen, Cambridge, MA. 2. Naismith RT, et al. CNS Drugs. 2020;34(2):185-196. doi:10.1007/ s40263-020-00700-0 3. Naismith RT, et al. Mult Scler. Published online November 4, 2019. doi:10.1177/1352458519881761

VUMERITY® (diroximel fumarate) delayed-release capsules, for oral use of the brain caused by the JC virus (JCV) that typically only occurs Brief Summary of full Prescribing Information in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who 1. INDICATIONS AND USAGE received dimethyl fumarate for 4 years while enrolled in a clinical trial.

VUMERITY is indicated for the treatment of relapsing forms of multiple During the clinical trial, the patient experienced prolonged lymphopenia sclerosis (MS), to include clinically isolated syndrome, relapsing- (lymphocyte counts predominantly <0.5 × 109/L for 3.5 years) while remitting disease, and active secondary progressive disease, in adults. taking dimethyl fumarate [see Warnings and Precautions (5.4)]. The patient had no other identified systemic medical conditions resulting 2. DOSAGE AND ADMINISTRATION in compromised immune system function and had not previously 2.1 Blood Tests Prior to Initiation of VUMERITY been treated with natalizumab, which has a known association with Obtain the following prior to treatment with VUMERITY: PML. The patient was also not taking any immunosuppressive or • A complete blood cell count (CBC), including lymphocyte count immunomodulatory medications concomitantly. [see Warnings and Precautions (5.4)] PML has also occurred in patients taking dimethyl fumarate in the • Serum aminotransferase, alkaline phosphatase, and total bilirubin postmarketing setting in the presence of lymphopenia (<0.9 × 109/L). levels [see Warnings and Precautions (5.5)] While the role of lymphopenia in these cases is uncertain, the PML 2.2 Dosing Information cases have occurred predominantly in patients with lymphocyte counts The starting dosage for VUMERITY is 231 mg twice a day orally. After <0.8×109/L persisting for more than 6 months.

7 days, the dosage should be increased to the maintenance dosage At the first sign or symptom suggestive of PML, withhold VUMERITY of 462 mg (administered as two 231 mg capsules) twice a day orally. and perform an appropriate diagnostic evaluation. Typical symptoms Temporary dosage reductions to 231 mg twice a day may be considered associated with PML are diverse, progress over days to weeks, and for individuals who do not tolerate the maintenance dosage. Within include progressive weakness on one side of the body or clumsiness 4 weeks, the recommended dosage of 462 mg twice a day should of limbs, disturbance of vision, and changes in thinking, memory, and be resumed. Discontinuation of VUMERITY should be considered orientation leading to confusion and personality changes. for patients unable to tolerate return to the maintenance dosage. Magnetic resonance imaging (MRI) findings may be apparent before Administration of non-enteric coated aspirin (up to a dose of 325 mg) clinical signs or symptoms. Cases of PML diagnosed based on MRI 30 minutes prior to VUMERITY dosing may reduce the incidence or findings and the detection of JCV DNA in the cerebrospinal fluid in severity of flushing [see Clinical Pharmacology (12.3)]. the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with 2.3 Administration Instructions Swallow VUMERITY capsules whole and intact. Do not crush or chew, PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent or sprinkle the capsule contents on food.

If taken with food, avoid a high-fat, high-calorie meal/snack; the with PML may be useful, and any suspicious findings should lead to meal/snack should contain no more than 700 calories and no more than further investigation to allow for an early diagnosis of PML, if present.

30 g fat [see Warnings and Precautions (5.6) and Clinical Pharmacology Lower PML-related mortality and morbidity have been reported following discontinuation of another MS medication associated with (12.3)].

PML in patients with PML who were initially asymptomatic compared to Avoid co-administration of VUMERITY with alcohol [see Clinical patients with PML who had characteristic clinical signs and symptoms Pharmacology (12.3)]. at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in 2.4 Blood Tests to Assess Safety After Initiation of VUMERITY Obtain a complete blood cell count (CBC), including lymphocyte count, disease in these patients.

6 months after initiation of VUMERITY and then every 6 to 12 months 5.3 Herpes Zoster and Other Serious Opportunistic Infections thereafter, as clinically indicated [see Warnings and Precautions (5.4)]. Serious cases of herpes zoster have occurred in patients treated Obtain serum aminotransferase, alkaline phosphatase, and total with dimethyl fumarate (which has the same active metabolite as bilirubin levels during treatment with VUMERITY, as clinically indicated VUMERITY) including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster [see Warnings and Precautions (5.5)]. meningomyelitis. These events may occur at any time during treatment.

2.5 Patients With Renal Impairment Monitor patients on VUMERITY for signs and symptoms of herpes No dosing adjustment is recommended in patients with mild renal zoster. If herpes zoster occurs, appropriate treatment for herpes zoster impairment. should be administered.

VUMERITY is not recommended in patients with moderate or severe Other serious opportunistic infections have occurred with dimethyl renal impairment [see Use in Specific Populations (8.6) and Clinical fumarate, including cases of serious viral (herpes simplex virus, Pharmacology (12.3)].

West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium 3. DOSAGE FORMS AND STRENGTHS VUMERITY is available as hard, delayed-release capsules containing tuberculosis) infections. These infections have been reported in 231 mg of diroximel fumarate. The capsules have a white cap and a patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, white body, printed with “DRF 231 mg” in black ink on the body. meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and 4. CONTRAINDICATIONS ear. Patients with symptoms and signs consistent with any of these VUMERITY is contraindicated in patients infections should undergo prompt diagnostic evaluation and receive • With known hypersensitivity to diroximel fumarate, dimethyl appropriate treatment. fumarate, or to any of the excipients of VUMERITY. Reactions Consider withholding VUMERITY treatment in patients with herpes may include anaphylaxis and angioedema [see Warnings and zoster or other serious infections until the infection has resolved [see Precautions (5.1)].

Adverse Reactions (6.2)].

• Taking dimethyl fumarate [see Drug Interactions (7.1)].

5.4 Lymphopenia 5. WARNINGS AND PRECAUTIONS VUMERITY may decrease lymphocyte counts. In the MS placebo5.1 Anaphylaxis and Angioedema controlled trials with dimethyl fumarate (which has the same active VUMERITY can cause anaphylaxis and angioedema after the first metabolite as VUMERITY), mean lymphocyte counts decreased by dose or at any time during treatment. Signs and symptoms in patients approximately 30% during the first year of treatment with dimethyl taking dimethyl fumarate (which has the same active metabolite as fumarate and then remained stable. Four weeks after stopping dimethyl VUMERITY) have included difficulty breathing, urticaria, and swelling fumarate, mean lymphocyte counts increased but did not return to of the throat and tongue. Patients should be instructed to discontinue baseline. Six percent (6%) of dimethyl fumarate patients and <1% of VUMERITY and seek immediate medical care should they experience placebo patients experienced lymphocyte counts <0.5 × 109/L (lower signs and symptoms of anaphylaxis or angioedema. limit of normal 0.91 × 109/L). The incidence of infections (60% vs 58%) and serious infections (2% vs 2%) was similar in patients treated with 5.2 Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has occurred in dimethyl fumarate or placebo, respectively. There was no increased infections observed in patients with lymphocyte patients with MS treated with dimethyl fumarate (which has the same incidence of serious 9 9 active metabolite as VUMERITY). PML is an opportunistic viral infection counts <0.8 × 10 /L or ≤0.5 × 10 /L in controlled trials, although one

patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5 × 109/L for 3.5 years) [see Warnings and Precautions (5.2)].

In controlled and uncontrolled clinical trials with dimethyl fumarate, 2% of patients experienced lymphocyte counts <0.5 × 109/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5 × 109/L with continued therapy. Neither VUMERITY® (diroximel fumarate) nor dimethyl fumarate have been studied in patients with preexisting low lymphocyte counts.

Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with VUMERITY, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of VUMERITY in patients with lymphocyte counts less than 0.5 × 109/L persisting for more than six months. Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if VUMERITY is discontinued or interrupted because of lymphopenia.

Consider withholding treatment from patients with serious infections until resolution. Decisions about whether or not to restart VUMERITY should be individualized based on clinical circumstances.

The data described in the following sections were obtained using dimethyl fumarate delayed-release capsules, which has the same active metabolite as VUMERITY. Adverse Reactions in Placebo-Controlled Trials with Dimethyl Fumarate In the two well-controlled studies demonstrating effectiveness, 1529 patients received dimethyl fumarate with an overall exposure of 2244 person-years [see Clinical Studies (14)].

The adverse reactions presented in Table 1 below are based on safety information from 769 patients treated with dimethyl fumarate 240 mg twice a day and 771 placebo-treated patients. The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for dimethyl fumarate were flushing, abdominal pain, diarrhea, and nausea.

Table 1: Adverse Reactions in Study 1 and 2 Reported for Dimethyl Fumarate at ≥2% Higher Incidence than Placebo

Adverse Reactions

Dimethyl Fumarate 240 mg Twice Daily (N=769) %

Placebo (N=771)%

5.5 Liver Injury Clinically significant cases of liver injury have been reported in patients 40 6 treated with dimethyl fumarate (which has the same active metabolite Flushing as VUMERITY) in the postmarketing setting. The onset has ranged Abdominal pain 18 10 from a few days to several months after initiation of treatment with 14 11 dimethyl fumarate. Signs and symptoms of liver injury, including Diarrhea elevation of serum aminotransferases to greater than 5-fold the upper Nausea 12 9 limit of normal and elevation of total bilirubin to greater than 2-fold 9 5 the upper limit of normal have been observed. These abnormalities Vomiting resolved upon treatment discontinuation. Some cases required Pruritus 8 4 hospitalization. None of the reported cases resulted in liver failure, Rash 8 3 liver transplant, or death. However, the combination of new serum 6 4 aminotransferase elevations with increased levels of bilirubin caused Albumin urine present by drug-induced hepatocellular injury is an important predictor of Erythema 5 1 serious liver injury that may lead to acute liver failure, liver transplant, Dyspepsia 5 3 or death in some patients.

Elevations of hepatic transaminases (most no greater than 3 times Aspartate aminotransferase 4 2 the upper limit of normal) were observed during controlled trials with increased dimethyl fumarate [see Adverse Reactions (6.1)].

Lymphopenia 2 <1 Obtain serum aminotransferase, alkaline phosphatase (ALP), and total bilirubin levels prior to treatment with VUMERITY and during Gastrointestinal treatment, as clinically indicated. Discontinue VUMERITY if clinically Dimethyl fumarate caused GI events (e.g., nausea, vomiting, diarrhea, significant liver injury induced by VUMERITY is suspected. abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and 5.6 Flushing VUMERITY may cause flushing (e.g., warmth, redness, itching, and/ usually decreased over time in patients treated with dimethyl fumarate or burning sensation). In clinical trials of dimethyl fumarate (which has compared with placebo. Four percent (4%) of patients treated with the same active metabolite as VUMERITY), 40% of dimethyl fumarate- dimethyl fumarate and less than 1% of placebo patients discontinued treated patients experienced flushing. Flushing symptoms generally due to gastrointestinal events. The incidence of serious GI events was began soon after initiating dimethyl fumarate and usually improved 1% in patients treated with dimethyl fumarate. or resolved over time. In the majority of patients who experienced Hepatic Transaminases flushing, it was mild or moderate in severity. Three percent (3%) of An increased incidence of elevations of hepatic transaminases in patients discontinued dimethyl fumarate for flushing and <1% had patients treated with dimethyl fumarate was seen primarily during serious flushing symptoms that were not life-threatening but led the first six months of treatment, and most patients with elevations to hospitalization. had levels <3 times the upper limit of normal (ULN) during controlled Administration of VUMERITY with food may reduce the incidence of trials. Elevations of alanine aminotransferase and aspartate flushing [see Dosage and Administration (2.3)]. Studies with dimethyl aminotransferase to ≥3 times the ULN occurred in a small number of fumarate show that administration of non-enteric coated aspirin (up to patients treated with both dimethyl fumarate and placebo and were a dose of 325 mg) 30 minutes prior to dosing may reduce the incidence balanced between groups. There were no elevations in transaminases or severity of flushing [see Clinical Pharmacology (12.3)]. ≥3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN. Discontinuations due to elevated hepatic transaminases 6. ADVERSE REACTIONS The following important adverse reactions are described elsewhere were <1% and were similar in patients treated with dimethyl fumarate or placebo. in labeling: • Anaphylaxis and Angioedema [see Warnings and Precautions (5.1)] Eosinophilia • Progressive Multifocal Leukoencephalopathy [see Warnings and A transient increase in mean eosinophil counts was seen during the Precautions Section (5.2)] first 2 months of therapy.

• Herpes Zoster and Other Serious Opportunistic Infections [see Adverse Reactions in Clinical Studies with VUMERITY Warnings and Precautions (5.3)] In clinical studies assessing safety in patients with RRMS, approximately • Lymphopenia [see Warnings and Precautions (5.4)] 700 patients were treated with VUMERITY and approximately • Liver Injury [see Warnings and Precautions (5.5)] 490 patients received more than 1 year of treatment with VUMERITY. • Flushing [see Warnings and Precautions (5.6)] The adverse reaction profile of VUMERITY was consistent 6.1 Clinical Trials Experience with the experience in the placebo-controlled clinical trials with Because clinical trials are conducted under widely varying conditions, dimethyl fumarate. adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may 6.2 Postmarketing Experience The following adverse reaction has been identified during post approval not reflect the rates observed in clinical practice.

use of dimethyl fumarate. 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.

Liver function abnormalities (elevations in transaminases ≥3 times ULN with concomitant elevations in total bilirubin >2 times ULN) have been reported following dimethyl fumarate administration in post marketing experience [see Warnings and Precautions (5.5)].

Herpes zoster infection and other serious opportunistic infections have been reported with dimethyl fumarate administration in postmarketing experience [See Warnings and Precautions (5.3)].

8. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of VUMERITY® (diroximel fumarate) or dimethyl fumarate (which has the same active metabolite as VUMERITY) in pregnant women. In animal studies, administration of diroximel fumarate during pregnancy or throughout pregnancy and lactation resulted in adverse effects on embryofetal and offspring development (increased incidences of skeletal abnormalities, increased mortality, decreased body weights, neurobehavioral impairment) at clinically relevant drug exposures [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.

17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).

Dosage and Administration Inform patients that they will be provided a starter dose bottle: one capsule twice a day for the first 7 days and then two capsules twice a day thereafter. Advise patients to take VUMERITY as instructed.

Inform patients to swallow VUMERITY capsules whole and intact.

Inform patients to not crush, chew, or sprinkle capsule contents on food. Inform patients that they should avoid a high-fat, high-calorie meal/snack at the time they take VUMERITY. If taken with food, the meal/snack should contain no more than 700 calories and no more than 30 g fat. Advise patients to avoid co-administration of VUMERITY with alcohol [see Dosage and Administration (2.2)].

Anaphylaxis and Angioedema Advise patients to discontinue VUMERITY and seek medical care if they develop signs and symptoms of anaphylaxis or angioedema [see Warnings and Precautions (5.1)].

Progressive Multifocal Leukoencephalopathy Inform patients that progressive multifocal leukoencephalopathy (PML) has occured in patients who received dimethyl fumarate, and therefore may occur with VUMERITY. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Inform the patient of the importance of contacting their healthcare provider if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms Data associated with PML are diverse, progress over days to weeks, and Animal Data include progressive weakness on one side of the body or clumsiness Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/ of limbs, disturbance of vision, and changes in thinking, memory, day) to pregnant rats throughout organogenesis resulted in a decrease and orientation leading to confusion and personality changes [see in fetal body weight and an increase in fetal skeletal variations at the Warnings and Precautions (5.2)]. highest dose tested, which was associated with maternal toxicity.

Plasma exposures (AUC) for MMF and HES (the major circulating drug- Herpes Zoster and Other Serious Opportunistic Infections related compound in humans) at the no-effect dose (100 mg/kg/day) Inform patients that herpes zoster and other serious opportunistic for adverse effects on embryofetal development were approximately infections have occurred in patients who received dimethyl fumarate 2 times those in humans at the recommended human dose (RHD) of and therefore may occur with VUMERITY. Instruct the patient of the importance of contacting their doctor if they develop any signs or 924 mg/day.

Oral administration of diroximel fumarate (0, 50, 150, or 350 mg/kg/ symptoms associated with herpes zoster or other serious opportunistic day) to pregnant rabbits throughout organogenesis resulted in an infections [see Warnings and Precautions (5.3)]. increase in fetal skeletal malformations at the mid and high doses and Lymphocyte Counts reduced fetal body weight and increases in embryofetal death and Inform patients that VUMERITY may decrease lymphocyte counts. A fetal skeletal variations at the highest dose tested. The high dose was blood test should be obtained before they start therapy. Blood tests are associated with maternal toxicity. Plasma exposures (AUC) for MMF also recommended after 6 months of treatment, every 6 to 12 months and HES at the no-effect dose (50 mg/kg/day) for adverse effects on thereafter, and as clinically indicated [see Warnings and Precautions embryofetal development were similar to (MMF) or less than (HES) (5.4) and Adverse Reactions (6.1)]. those in humans at the RHD. Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/day) Liver Injury to rats throughout gestation and lactation resulted in reduced weight, Inform patients that VUMERITY may cause liver injury. Instruct which persisted into adulthood, and adverse effects on neurobehavioral patients treated with VUMERITY to report promptly to their healthcare function in offspring at the highest dose tested. Plasma exposures provider any symptoms that may indicate liver injury, including fatigue, (AUC) for MMF and HES at the no-effect dose for adverse effects on anorexia, right upper abdominal discomfort, dark urine, or jaundice. A postnatal development (100 mg/kg/day) were approximately 3 times blood test should be obtained before patients start therapy and during treatment, as clinically indicated [see Warnings and Precautions (5.5)].

(MMF) or similar to (HES) those in humans at the RHD. Flushing and Gastrointestinal (GI) Reactions 8.2 Lactation Flushing and GI reactions (abdominal pain, diarrhea, and nausea) are Risk Summary There are no data on the presence of diroximel fumarate or metabolites the most common reactions, especially at the initiation of therapy, and (MMF, HES) in human milk. The effects on the breastfed infant and on may decrease over time. Advise patients to contact their healthcare provider if they experience persistent and/or severe flushing or GI milk production are unknown. reactions. Advise patients experiencing flushing that taking VUMERITY The developmental and health benefits of breastfeeding should be with food (avoid high-fat, high-calorie meal or snack) or taking a nonconsidered along with the mother’s clinical need for VUMERITY and enteric coated aspirin prior to taking VUMERITY may help [see Dosage or drug the from infant breastfed the on effects any potential adverse and Administration (2.2) and Adverse Reactions (6.1)]. from the underlying maternal condition.

Pregnancy 8.4 Pediatric Use to become pregnant Safety and effectiveness in pediatric patients have not been Instruct patients that if they are pregnant or plan their healthcare provider inform should they VUMERITY taking while established. [see Use in Specific Populations (8.1)].

8.5 Geriatric Use Clinical studies of dimethyl fumarate and VUMERITY did not include 54499-02 sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.

Manufactured for: Biogen Inc. 8.6 Renal Impairment MA 02142 No dosage adjustment is necessary in patients with mild renal Cambridge, major a of exposure impairment. Because of an increase in the is a registered trademark of Biogen. metabolite [2-hydroxyethyl succinimide (HES)], use of VUMERITY is VUMERITY - 2020 not recommended in patients with moderate or severe renal impairment © Biogen 2019 [see Clinical Pharmacology (12.3)].

Conferences & Community

AAN Awarded Grant for Anti-racism Training for Neurologists The AAN was awarded a grant from the Health Equity Innovation Fund, one of two funds provided by Genentech and the Genentech Foundation to support groundbreaking solutions to promote health equity and diversity in STEM from kindergarten to career.

One of 40 recipients, the AAN is the only neurologyfocused organization chosen for the Health Equity Innovation Fund grant. Nearly 380 academic institutions, health systems, nonprofits, patient groups, think tanks, and community organizations applied for the grants.

The AAN recognizes that the field of neurology currently is not representative of the US population and has identified groups that are underrepresented in neurology (UIN), specifically Black people. The AAN has identified the need for immediate action to address the lack of neurologists from these groups that are underrepresented in neurology. The grant will enable the AAN to develop a multifaceted anti-racism core curriculum and training unique for neurologists. The training program will launch in late 2021 and continue into 2022.

“With the financial support from Genentech, the AAN can further demonstrate its commitment to Inclusion, Diversity, Equity, Anti-racism, and Social Justice and make lasting change in the field of neurology,” said Jeffrey C. McClean II, MD, FAAN, Lt. Col., USAF, MC, and chair of the AAN Equity, Diversity & Inclusion Joint Coordinating Council. “By providing yearlong curriculum for its members the AAN is highlighting its dedication to be an anti-racist organization. As a longtime member of the AAN and someone involved with this work I am excited to see these important initiatives move forward.”

The anti-racism training program will be offered for free to AAN members in the US and will encompass three aims: increase the placement and retention of individuals underrepresented in neurology in academic neurology departments, with a specific emphasis on increasing and supporting individuals UIN in the neurologic research area; increase the McClean number of individuals UIN serving as faculty in academic neurology departments; and increase the number of individuals UIN serving in academic neurology department leadership.

“We can no longer ignore the systemic inequities in our healthcare and education systems that have been laid bare by the pandemic,” said Kristin Campbell Reed, executive director, Genentech Corporate and Employee Giving and The Genentech Foundation. “We need bold, action-oriented approaches to target the root causes of these issues, which is why we’re so excited to support organizations across the country that can offer a real chance at progress."

This anti-racism training program supports the AAN’s core value―Inclusion, Diversity, Equity, Anti-racism and Social Justice (IDEAS)―in which the organization commits to intentional action to be a fully inclusive, deliberately diverse, and anti-racist organization that respects and values our membership, our staff, and the communities we serve. 

AANnews • April 2021 23

Tools & Resources

Compensation and Productivity Survey Delivers Reliable, Usable Data Past Neurology Compensation and Productivity Surveys have benefited thousands of US AAN members, including Chris Liekweg, MBA, at Virginia Commonwealth University. “Being part of an academic medical center often requires reliable subspecialty benchmarking data to convey accurate performance metrics to key internal stakeholders,” said Liekweg. “This data set has enabled us to effectively communicate the appropriate targets whether they be productivity-related or compensation-based.”

The 2021 Neurology Compensation and Productivity Survey is now open to US AAN members. Benchmark your value using the largest neurology compensation survey in the United States and receive free access to the full data dashboard—a $500 value member value—if you complete the survey by May 14, 2021. Participation also includes immediate download of historical 2019 data upon survey submission.

Enhancements have been made to the survey to save you time and help you get the most out of the data. As in previous years, the AAN is committed to protecting your anonymity, and we can assure you that collected data is de-identified and reported only in aggregate.

Discover the advantages of the Neurology Compensation and Productivity Survey data: Benchmark neurologist and APP compensation and productivity Compare by subspecialty

Review ancillary services to find new opportunities for your practice

Liekweg

Find out how other practices perform Find out average size of other practices and their use of APPs employee mix Discover the payer mix for neurological practices Benchmark practice manager compensation working in neurologic practice settings For convenience, a downloadable spreadsheet enables practice managers to import data on behalf of the neurologists in a practice. Simply log in and download the survey spreadsheet, fill it out, and upload data. There is an option to save the spreadsheet to make data entry easier for the next survey.

Learn more and begin the survey by visiting AAN.com/Benchmark. 

Benchmark on-call rates and duties Gauge demand for neurological services using total patient encounters and appointment wait times

Visit Axon Registry Virtual Booth During Annual Meeting The AAN’s fully virtual Annual Meeting will be held April 17 through 22, and the staff of the Axon Registry ® invite you to “stop by” their virtual registry booth where they will be happy to answer questions from current participants and members who are curious about the registry.

More than 30 EHR systems are compatible with the Axon Registry. EPIC integration has been successful across several large health care institutions and academic medical centers across the nation. Currently, there are over 50 measures in the Axon Registry that cover a wide variety of neurologic disease states. Academy staff are happy to provide more information on measures, continuing certification, MIPS submission, and other benefits of Axon Registry participation.

AAN members can request a specific time to meet registry staff at the Axon Registry booth by emailing registry@aan.com.

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AANnews • April 2021

Two talks focused on the Axon Registry and quality improvement will be offered in the Experiential Learning Area Pioneering Practice, Policy, and Performance: Staying Ahead of Change: Wednesday, April 21, 5:00 p.m.–5:20 p.m. ET Lessons from the California Parkinson’s Disease Registry and What’s Next? / How to Successfully Publish Quality Improvement Projects Allan Ding Wu, MD, FAAN, and Anup D. Patel, MD, FAAN Wednesday, April 21, 6:00 p.m.–6:20 p.m. ET Using the Axon Registry to Ease Your Data-collection Burden Laurice T. Yang, MD, MHA, and Susan T. Herman, MD, FAAN 

Business Support Network Launched to Help Business Administrators It’s not unusual for neurology practice business administrators (BAs) to have questions or need advice about matters that come up during the workday. To help connect them with fellow BAs who might have the answers they seek, the AAN is debuting the Business Support Network. The network is comprised of six AAN business administrator members representing a variety of practice settings and areas of expertise. They are available to help answer practice-related questions and share their experiences related to various topics and scenarios. The Academy hopes BAs find this resource a meaningful way to build their professional networks and get support to help their practices thrive.

To reach this network, email practice@aan.com. This inbox is monitored by AAN staff who usually respond within one business day. Staff also can help answer practice-related questions regarding practice management and operations, coding, the quality payment program, payer issues, and more. When staff reach out to the Business Support Network, questions are

Business Support Network Email practice@aan.com to: Reach business administrator network Get your practice-related questions answered Build your professional network

stripped of identifying information for anonymity. In this way, BAs are free to ask potentially sensitive questions. Staff compile network insights and email back the inquirer, including network contact information when appropriate.

The Business Support Network is an expansion of the AAN’s successful Practice Support Network comprised of physician graduates of the Practice Leadership Program who also help answer questions submitted to the practice@aan.com inbox. 

Navigating E/M Coverage in 2021 2021 brought about the most significant changes to the way outpatient E/M services are reported in over 20 years. As we get further into the year, questions have arisen concerning private payers’ audit procedures for outpatient E/M under the new documentation guidelines. While many payers are working through new workflows and are trying to figure out the exact way they will audit these services, the AAN continues to communicate with them to understand their auditing process.

The Coding and Payment Policy Subcommittee has compiled some helpful tips for working with payers: When billing based on time, remember to include total (both face-to-face and non-face-to-face) time on the day of the encounter.

As the revised documentation guidelines do not stipulate specifically how time is to be captured in the medical record, take note of any payer-specific requirements.

When coding based on medical decision making (MDM), we recommend not to include time in your documentation.

If time is documented, payers may misinterpret this as time-based billing and this could result in delayed claims processing or denials.

Also new in January 2021 were prolonged service codes 99417 and G2212 for time spent beyond the standard level 5 outpatient visits. While both codes are used for increments of 15 minutes

of additional time, it is important to note the threshold to report each code differs as does payer coverage of each code. When submitting a claim for prolonged services it is imperative to first check with your payer to see what codes are covered, in addition to which type of policy the patient has. Medicare Advantage plans generally follow Medicare guidelines and will cover G2212, whereas commercial payers may be able to accept either code G2212 or 99417. It always is recommended to review your payers’ policy regardless of Medicare Advantage, Medicaid, or commercial payer or check with your provider representative to see what codes they can accept.

The AAN is here to help our members navigate any potential claims denials and help them identify options for submitting a corrected claim or appeal. Contact AAN staff at practice@ aan.com for answers to your questions concerning outpatient E/M coding, payer relations, and to share your experiences with payers that might benefit your neurology colleagues. 

Prolonged Service Codes 99417 and G2212

99417: Prolonged office or other outpatient evaluation and management service(s) beyond the minimum required time of the primary procedure which has been selected using total time, requiring total time with or without direct patient contact beyond the usual service, on the date of the primary service, each 15 minutes of total time G2212: Prolonged office or other outpatient evaluation and management service(s) beyond the maximum required time of the primary procedure which has been selected using total time on the date of the primary service; each additional 15 minutes by the physician or qualified healthcare professional, with or without direct patient contact 

Tools & Resources

COVID-19 Topics Populate New Neurology: Clinical Practice Issue Volume 11,

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The new issue of Neurology ® Clinical Practice offers the editorials “Cognitive Screening in Aging Physicians: Faith in Numbers,” by Lawrence J. Whalley, MD; and “Going Viral: Lessons from Disaster Medicine for the Neurologist in the COVID-19 Era,” Jack W. Tsao, MD, DPhil, FAAN. Case studies related to the COVID-19 pandemic include “Interventional Stroke Management in a COVID-19 Patient,” by Amer Alshekhlee, MD; “Bilateral Brachial Neuropathies Following Prone Ventilation for COVID-19 Pneumonia,” by Neil E. Anderson, MD; “Effects of COVID-19 “Sheltering in Place” on Activity in People with Multiple Sclerosis,” by Bruce Anthony Campbell Cree, MD, PhD, MCR, FAAN; and “Fatal Necrotizing Encephalitis Associated with COVID-19: A Case Report,”

by Anne-Cécile Morvan, MD. Published six times a year, Neurology: Clinical Practice is available free to all AAN members online and in print for US members only. Visit Neurology.org/cp for more information. 

Practice Top 5 Lists Newly Updated The AAN’s Practice Top 5 lists are a great way to help manage complex practice issues. Each list is a quick, actionable resource, distilling each topic down to the Top 5 things members need to know. They also include links to resources for those who want to dive deeper.

New Top 5 lists are published throughout the year and have been recently updated to ensure members are getting the most relevant information to help their practices thrive. Below is a recently published example.

Top 5: Things Administrators Need Their Physicians to Know 1. HIPAA compliance is still a thing and your phone may be putting you and the practice at risk. Texting patient health information has been and will remain a non-HIPAA compliant action. Making verbal phone calls or faxing this information is much more HIPAA compliant and will not leave the practice exposed to liabilities. There are HIPAAcompliant texting apps that can be installed on PCs and smartphones that make this process much safer.

2. Proper E/M coding can help profitability, is important, and yet not always easy for physicians to know all the nuances of the coding guidelines. Ensure that the services provided are correctly documented to support the billable code that reimburses at the appropriate level for that work and to avoid under coding, which can impact profitability. The AAN has templates to help calculate E/M points, identify where billing and codes can be escalated and why, and guide documentation to maximize reimbursement.

3. Harness the power of promotion. Promoting yourself and harnessing the power of patients promoting your work can be a key differentiator for your business. If someone is extremely happy with you or your office's services, ask them to leave a review online. Prospective patients do read these, and while they are not the ultimate factor of why patients choose your

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AANnews • April 2021

practice, good ratings certainly do help.

4. Stay in tune with your MIPS quality measures. It is critical to understand how measure selection and calculation impacts overall MIPS scoring that drives the reimbursement calculation. And timing matters! MIPS quality measures now require one year of continuous calculations and getting behind on them can mean the difference between a positive or negative payment adjustment. Physicians should work with their admin and IT teams and give them the support to review numbers and adjust workflows to maximize scoring.

5. Consider adding more auxiliary staff to the practice. If the physician’s day-to-day activities are becoming more administrative or clinical task-oriented, consider adding auxiliary staff such as medical assistants, social workers, pharmacists, APPs, etc., to the team. Adding auxiliary staff can not only improve efficiencies and expand service lines, but it can also improve the quality of life for the physicians.

Additional Top 5 topics can be found at AAN.com/Top5 including: Billing and coding Regulatory rules, such as HIPAA and information blocking Practice management, such as patient access, building a referral network, and critical monthly EHR reports Value-based care, including MIPS categories and valuebased contracts 

Late Talk Show Host Larry King Memorialized in New Brain & Life

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Vaccines swer Experts Antions Your Ques Wellness How Music e Helps Thosntia with Deme Epilepsy ents New Treatm g and Promisin Research

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st lk show ho ws, the ta last intervie m a stroke In one of his covered fro re he w ho describes

Larry King, the former host of Larry King Live on CNN, died from sepsis on January 23, 2021, after dealing with several health problems, including COVID-19 in early January and a stroke in 2019. In one of his last interviews before his death, he spoke with Brain & Life® about his recovery from a near-fatal stroke and how his experience shifted his perspective on dying.

In continuing coverage of the pandemic, readers’ questions and concerns about the COVID-19 vaccines are addressed, including how the mechanism of the Moderna and Pfizer vaccines differs from traditional vaccines, what to expect, and how to prepare.

NASCAR driver Matt Tifft discusses his diagnosis of epilepsy in another feature, which also looks at the latest developments in treatment.

Join the latest AAN online community open to all members—the Quality and Safety Synapse™ Community.

The goals of this community are to provide a forum to share quality improvement results, successes, and evidence-based best practices and tools; shape a culture Jones of quality and foster quality improvement collaboration within organizations; and serve as a venue for getting more people interested in participating in quality improvement.

“Neurologists are committed to delivering high-quality care to their patients, and many neurology practices and departments have identified clinical leaders for their quality improvement work,” said Lyell K. Jones, Jr., MD, FAAN, chair of the Quality Committee. “Until now there hasn’t been a forum for these QI clinical leads and experts to collaborate with their peers, and we hope this Synapse community provides a venue to share QI insights. In the spirit of quality improvement, everyone doesn’t need to reinvent the same wheel.”

Visit AAN.com/view/Sections and search for the Quality and Safety Synapse Community. 

Brain & Life also provides an in-depth look at frontotemporal dementia and why there’s reason for hope for families affected by this devastating disease.

Brain & Life magazine is free for AAN members in the United States to distribute to patients, who also can subscribe for free. If you would like to adjust the number of copies you receive for your patients or update your clinic address, email BeGreen@WasteFreeMail.com. All members have online access to the magazine articles and additional resources at BrainandLife.org. Please share the website with your patients! 

AANnews • April 2021 27

Education & Research

New Continuum Examines the Latest Information in Neuro-otology Developments in addressing neuro-otology are the focus of the new issue of Continuum: Lifelong Learning in Neurology®.

According to Guest Editor Terry D. Fife, MD, FAAN, FANS, “Since the last Continuum issue on neuro-otology in 2012, refinements have been made to improve the value of the history of patients with dizziness. Neurologists should reduce the emphasis on the description of dizziness (eg, vertigo or lightheadedness) and consider with equal importance the timing and duration of spells and any circumstances that induce the dizziness.”

Topics covered in this issue include:

Continuum RN ING LIF ELO NG LEA

Approach to the History and Evaluation of Vertigo and Dizziness Terry D. Fife, MD, FAAN, FANS

®

GY IN NE UROLO

APRIL 2021

VOL. 27

Episodic Positional Dizziness Kevin A. Kerber, MD, MS

NO. 2

Neuro-otology

Episodic Spontaneous Dizziness Scott D.Z. Eggers, MD

MD, FA AN N L. LEWIS , CHIEF: STEVE AN, FANS EDITO R-INFIFE, MD, FA R: TERRY D. GUES T EDITO

Acute Vestibular Syndrome Kristen K. Steenerson, MD Chronic Dizziness Yoon-Hee Cha, MD, FAAN Vertigo Related to Central Nervous System Disorders Kamala Saha, MD

CONT INUUM

PODCAST

JOURN AL.CO

M

Selected Otologic Disorders Causing Dizziness Gail Ishiyama, MD Tinnitus, Hyperacusis, Otalgia, and Hearing Loss Terry D. Fife, MD, FAAN, FANS Roksolyana Tourkevich, MD

Fife

The issue includes a postreading selfassessment and test with the opportunity to earn up to 20 AMA PRA Category 1 Credits™ toward Self-assessment CME. Upcoming topics for 2021 include: June: Headache August: Neuroinfectious Disease October: Neurocritical Care December: Behavioral Neurology and Psychiatry From April 1 through June 30, AAN members pay only $339 per year for a subscription to Continuum® and Continuum® Audio, which is a 15-percent discount on the already low AAN member rate of $399. Subscribe or renew by contacting Wolters Kluwer at (800) 3610633 or (301) 223-2300 (international) or visit shop.LWW.com/continuum to get this discounted rate. AAN Junior members who are transitioning to neurologist memberships are eligible to receive a 60-percent discount on the already low member rate for the Continuum and Continuum Audio subscription. 

Neurology ® Podcast:

20 Minutes Pack a Punch!

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

28

AANnews • April 2021

2021 RITE Sees Record Participation in Midst of COVID, Test Changes In response to the challenges related to COVID-19, the AAN worked closely with residents, program directors, and program coordinators to develop and implement a new way of delivering and taking the 2021 RITE® (Residency Inservice Training Exam) in February.

their homes—and on any day during the testing window period. For the first time in its 23 years, the exam was not administered in a proctored environment. As in previous years, program coordinators provided the bulk of support for residents taking the test.

RITE dates were extended to two-anda-half weeks to allow for flexibility for exam administration and physical distancing given the ongoing COVID-19 pandemic. Residents were also allowed to take the exam on their personal devices, from any location—including

Despite the new delivery format and a number of last-minute changes to ensure maximum safety of all involved, a record number of more than 3,000 residents representing 230 programs worldwide took part in the popular opportunity to assess their current

level of knowledge in neurology and neuroscience, identify areas for potential growth, and track their progression throughout their residency. 

2021 UCNS Continuous Certification Reading List Available The United Council for Neurologic Subspecialities’ 2021 continuous certification (C-cert) reading lists are now available for Autonomic Disorders, Behavioral Neurology & Neuropsychiatry, Clinical Neuromuscular Pathology, Headache Medicine, Neurocritical Care, Neuroimaging, and Neurooncology. Reading lists include links to the journal articles or abstracts submitted by subspecialty peers and selected by each subspecialty’s certification examination committee based on specific criteria.

on the latest science, treatments, and therapeutics relating to their subspecialty and include completing the reading lists and taking and passing the 25-question online post-reading quiz to assess knowledge gained from the journal article content.

UCNS certification is continuous and does not expire when diplomates meet the annual C-cert requirements.

Learn more and access the C-cert reading lists at UCNS.org/ReadingLists. 

C-cert activities provide subspecialty learning and knowledge assessment to ensure that diplomates are staying up to date

AANnews • April 2021 29

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

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 the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. 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  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 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

MORE THAN

APPROXIMATELY

200,000

15 YEARS OF EXPERIENCE

NEW PATIENTS

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

in clinical trials and real-world use. Biogen is committed to patient safety through the TOUCH® Prescribing Program

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

PATIENTS TREATED

1 IN 3

DMT=disease-modifying therapy; a202,300 patients as of August 20193; b36.9% of patients as of April 2020. 4

VISIT TimeForTYSABRI.com IMPORTANT SAFETY INFORMATION (cont’d) WARNING: Progressive Multifocal Leukoencephalopathy (PML) (cont’d)  Adverse events that may occur during plasma exchange (PLEX) include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although PLEX has not been prospectively 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. There is no evidence that PLEX has any benefit in the treatment of opportunistic infections such as PML  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 PLEX 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 PLEX. 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  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 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) 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 Thrombocytopenia  Cases of thrombocytopenia, including immune thrombocytopenic purpura (ITP), have been reported with the use of TYSABRI in the postmarketing setting. Symptoms of thrombocytopenia may include easy bruising, abnormal bleeding, and petechiae. Delay in the diagnosis and treatment of thrombocytopenia may lead to serious and life-threatening sequelae. If thrombocytopenia is suspected, TYSABRI should be discontinued 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 June 2020, Biogen. © 2020 Biogen. All rights reserved. 07/20 TYS-US-2311 v3

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 the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. 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: • The presence of anti-JCV antibodies. Patients who are anti-JCV antibody positive have a higher risk for developing PML. • Longer treatment duration, especially beyond 2 years.

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

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

1/10,000

1-24 months 25-48 months 49-72 months 73-96 months

Anti-JCV Antibody Positive No Prior Prior Immunosuppressant Immunosuppressant Use Use <1/1,000 1/1,000 2/1,000 6/1,000 4/1,000 7/1,000 2/1,000 6/1,000

Notes: The risk estimates are based on postmarketing data in the United States from approximately 100,000 TYSABRI exposed patients.

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 (PLEX), 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 half-lives) 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 PLEX 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 PLEX include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although PLEX has not been prospectively 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. There is no evidence that PLEX has any benefit in the treatment of opportunistic infections such as PML. 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 PLEX 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 PLEX. 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. Thrombocytopenia Cases of thrombocytopenia, including immune thrombocytopenic purpura (ITP), have been reported with the use of TYSABRI in the postmarketing setting. Symptoms of thrombocytopenia may include easy bruising, abnormal bleeding, and petechiae. Delay in the diagnosis and treatment of thrombocytopenia may lead to serious and life-threatening sequelae. If thrombocytopenia is suspected, TYSABRI should be discontinued.

5.9. 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)

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, thrombocytopenia (including immune thrombocytopenic purpura).

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)].

Thrombocytopenia Inform patients that Tysabri may cause a low platelet count, which can cause severe bleeding that may be life-threatening. Instruct patients to report any symptoms that may indicate thrombocytopenia, such as easy bruising, prolonged bleeding from cuts, petechiae, abnormally heavy menstrual periods, or bleeding from the nose or gums that is new [see Warnings and Precautions (5.8)].

TYSABRI (natalizumab) Manufactured by: Biogen Inc. Cambridge, MA 02142 USA US License No. 1697 © 2015-2020 Biogen Inc. All rights reserved.

06/2020 U.S. Patent Numbers: 5,840,299; 6,602,503

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.

CMS Adjusts MIPS Penalties Due to COVID-19 Health Emergency

On February 25, the Centers for Medicare & Medicaid Services (CMS) announced it will hold MIPS eligible clinicians harmless from up to nine percent in penalties due to the impact of the COVID-19 public health emergency on performance in 2020. The Extreme and Uncontrollable Circumstances Hardship Exception policy will be automatically applied to all MIPS eligible clinicians who do not submit any MIPS data for the 2020 performance period and avoid a 2022 payment penalty. CMS is also reopening the hardship exception application with a deadline of March 31, 2021. Groups and eligible clinicians who submit data in at least 21 Patient Reported Outcome Measures Ad—Half Page Horizontal> AN d in AANnewstwo MIPS categories will override the hardship exception and be eligible 5.25 +0.125 bleed, 4C to earn a bonus from the exceptional performance bonus pool or potentially be subject to a penalty.

Academy Queries SSA on Disability Processes On February 23, the AAN submitted a letter to the Social Security Administration (SSA) related to the disability determination process for both neurologist medical experts and for neurology patients. The letter raised significant issues related to the rate of compensation for medical experts and the burdens of the process to become a medical expert. The letter also noted evidence of significant inequities in the disability determination process that detrimentally impact neurology patients. The goal of the letter is to open a dialogue with the SSA and to ascertain the degree to which legislative action is needed to ensure that neurology patients can access necessary and appropriate benefits. 

Make Your Patient Your Partner Invest in the outcomes that matter most to your patients. Learn about common Patient Reported Outcome (PRO) scales and tools used in neurology at AAN.com/PRO.

Education & Research

Participants Sought for New COVID-19 Neuro Databank/Biobank NYU Langone Health, with the support of the National Institute of Neurological Disorders and Stroke, has established the COVID-19 Neuro Databank/Biobank (collectively called “NeuroCOVID”). There is accumulating evidence of COVID-19associated neurologic symptoms. Especially in cases where symptoms may be relatively rare, only via a comprehensive database, rather than isolated case reports, will a clear picture emerge of the constellation of neurologic effects, their mechanisms, and outcomes.

The goal of this data repository is to collect patient-level data contributed directly by practitioners on neurologic involvement in patients with COVID-19 illness. It will also accommodate submission of medical record data or previously collected datasets. The NeuroDatabank will serve as an international resource, with data shared in accordance with the NIH datasharing policy and made broadly available for analyses. Data standards have been implemented to assure that this database is aligned with other similar international efforts.

The project seeks data and biospecimens from individuals across the lifespan, from neonates to older adults, including pregnant women and mother/infant dyads and information from a broad spectrum of populations, including the underserved and vulnerable. Researchers are particularly interested in documenting the effects of COVID-19 on those with pre-existing neurologic disorders.

Patient confidentiality will be protected by use of a global unique identifier (GUID), so that the database will not contain personally identifiable information.

Visit the NeuroCOVID website for more information about how to join this project, and access to the COVID-19 Neuro Database/Biobank. 

The NeuroBiobank biospecimen repository will collect and store biospecimens, linked to these patients’ NeuroDatabank data. Biospecimens that are stored outside NYU Langone Health at other sites also will be logged and tracked.

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Complete the 2021 Neurology Productivity and Compensation Survey The A

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THE FOR Benchmark your value using the largest neurology

compensation survey in the United States. FIND A JOB

Complete the survey by May 14, 2021 Learn m

to receive FREE access to the full data dashboard— a $500 AAN member value!

Start the survey at AAN.COM/BENCHMARK

Dates & Deadlines

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APRIL 1

Applications Deadline: UCNS Clinical Neuromuscular Pathology Certification UCNS.org/CNMPcertification

APRIL 17–22

2021 AAN Annual Meeting AAN.com/21AM

APRIL 17

2021 AAN Business Meeting AAN.com/21AM

APRIL 19

Virtual Career Fair Careers.aan.com

APRIL 21

AAN Trainee Trivia: Online Neurology Contest https://bit.ly/3qr2OXi

24 23 30 31

MAY 3

Application Deadline: UCNS Neurocritical Care Certification UCNS.org/NCCcertification

MAY 10

Abstract Submission Deadline: Sports Concussion Conference AAN.com/SCC

MAY 13

Applications Open: UCNS Neurocritical Care Certification UCNS.org/NCCcertification

MAY 14

Deadline: Neurology Compensation and Productivity Survey AAN.com/Benchmark

MAY 19

Neurology on the Hill Virtual Event AAN.com/NOH

Careers.aan.com

d—Full Page> AANnews, NJ, NCP urology Journal, or Neurology Clinical Practice d, 4C

Visit the AAN’s Neurology Career Center to view hundreds of additional jobs and sign up for customized, confidential notifications when positions of interest are added.

American Academy of Neurohospitalist – Neurology - UCI School of Medicine rology is—Orange, proudCalifornia to offer

#1 CAREER CENTER NEUROLOGISTS

D

The University of California (UC), Irvine, Department of Neurology is recruiting two BC/BE faculty members to develop a dedicated Neuro-hospitalist Program at the UC Irvine Medical Center in Orange, California. We prefer that the

RECRUIT TOP TALENT

more! Careers.AAN.com

successful candidates will have outstanding training in inpatient care of complex neurological disorders, with fellowship training in Neurohospitalist program, Stroke or Neurocritical Care. The academic appointment is expected to be at the Assistant or Associate Professor level in the Clinical Health Science Series. Salary will be commensurate with training and experience. Successful candidates will work closely with our Comprehensive Stroke and Cerebrovascular Center, and a multidisciplinary team of subspecialists including neurologists, neuro-intensivists, neuro-interventionalists, cerebrovascular surgeons, and neuro-radiologists. Substantive inquiries about the position should be directed to: Claire Henchcliffe, MD, DPhil, Professor and Chair, Department of Neurology, 200 S. Manchester Ave. Ste 206, Orange, CA 928684280 Requirements: Applications are being sought from candidates who possess M.D. or M.D./Ph.D. degrees in the field of Neurology or equivalent who are eligible for licensure by the California Medical Board. Candidates must have demonstrated capabilities for teaching, professional service and/or research suitable to the HS Clinical Professor series. The incumbent will participate in patient care, teach residents and students, perform university and public service, and demonstrate professional competency and activity. Positions are dependent upon funding. Salary and rank will be commensurate with qualifications and experience. Initial appointments are for one year and renewal is based on availability of support.

TO APPLY: Please log onto UCI RECRUIT located at: https:// recruit.ap.uci.edu/JPF06549 Applicants should complete an online application profile and upload the following application materials electronically to be considered for the position: Cover letter, Curriculum Vitae, Teaching Statement, Statement of Contributions to Diversity, Contact Information for 3-4 Referees. The University of California, Irvine is an Equal Opportunity/Affirmative Action Employer advancing inclusive excellence. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, protected veteran status, or other protected categories covered by the UC nondiscrimination policy.

AANnews® Classified Advertising The AAN offers a complete package of print, online, and in-person recruitment advertising opportunities.

Visit careers.AAN.com for all AAN options, rates, and deadlines.

Ad copy for the June 2021 print edition of AANnews must be submitted by May 1, 2021. The same deadline applies to changes/cancellations.

The American Academy of Neurology reserves the right to decline, withdraw, or edit advertisements at its discretion. Every care is taken to avoid mistakes, but the responsibility for clerical or printer errors does not exceed the cost of the ad. 

AANnews • April 2021 39

American Brain Foundation

Celebrate and Support Advances in Brain Disease Research at Commitment to Cures Gala Join your friends and colleagues for a night of fun to celebrate advances in brain disease research at the American Brain Foundation’s 2021 Commitment to Cures gala, set to take place virtually on Wednesday, April 21, during the AAN Annual Meeting.

A star-studded lineup of honorees will be on hand—including CNN Chief Medical Correspondent and neurosurgeon Sanjay Gupta, MD; Cindy McCain, widow of late US Sen. John McCain; Jim Cramer, host of CNBC’s Mad Money; and entrepreneur, advocate, and reality television star Khloé Kardashian—and attendees will have many opportunities to engage in fun-filled, interactive activities and entertainment throughout the night.

Mixologist Tamu Curtis, founder and president of The Cocktailery, will lead attendees through a hands-on cocktail demonstration.

Attendees should order their Celebration Gift Box when buying event tickets in order to have cocktail ingredients shipped directly to their doors and on-hand for the demo.

Interested attendees can also enter into a raffle for a chance to get whisked away to beautiful Tuscany. The travel package includes a trip to charming Cortona—the setting for the popular book and movie Under the Tuscan Sun—and includes a wine tasting and private dinner.

Rounding out the memorable night will be a live musical performance by Alex Newell, Grammy-nominated singer, songwriter, and activist.

Funds raised from the 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.

Visit AmericanBrainFoundation.org/C2C2021 to learn more and to secure your ticket or contact events@americanbrainfoundation. org or (866) 770-7570 for more information. 

Spring Special:

Only $339 for AAN Members!

Join your colleagues who depend on Continuum® and Continuum® Audio to stay informed on the latest in patient care.

Subscribe or renew by June 30 and save 15% off the regular rate with code WMQ074AA. Lock in this rate for up to 3 years.

SPINAL CORD DISORDERS FEBRUARY 2021, VOL 27, NO 1

40

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AANnews • April 2021 1-PM028

April 21, 2021 • 8–9pm ET

Sanjay Gupta, MD Public Leadership in Neurology Award

Cindy McCain Commitment to Cures Award

Khloé Kardashian Ambassador Award

Jim Cramer Master of Ceremonies

GET READY FOR A STAR-STUDDED EVENT. THANK YOU TO OUR PRESENTING SPONSOR

Don’t miss out on Commitment to Cures, a virtual event dedicated to celebrating and supporting advances in brain disease research. The evening will feature celebrity guests, a musical performance

by Grammy-nominated singer and songwriter, Alex Newell, a craft cocktail demo, inspiring stories from those impacted by brain disease, and more!

Register now at americanbrainfoundation.org/C2C2021