2021 November AANnews

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VOLUME 33  ·  ISSUE 11  ·  NOVEMBER 2021

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

2022 ANNUAL MEETING REGISTRATION NOW OPEN! Join Us at the Great Neuro Reunion Get ready to reunite in person with your neurology community at the Annual Meeting’s Great Neuro Reunion April 2–7 in Seattle, followed by the unique, interactive Annual Meeting: Virtual Experience April 24–26. Whether you join us in Seattle, virtually, or both, you’ll find a fresh lineup—of top-tier education opportunities in every topic, all the valuable CME you need, the most cutting-edge science covering every subspecialty, and the opportunity to reconnect with friends and colleagues from around the world. Get the best value, and a 25-percent discount, using the Platinum registration package, which includes registration to both events and extended access to recordings from both meetings. Visit AAN.com/AM to learn more about registration packages, the latest Annual Meeting updates, Seattle happenings, and more! 

Seattle: April 2 –7 Virtual Experience: April 24–26

There’s Still Time to Register for the November 5–7 Virtual Fall Conference

AAN Membership Offers Access to Valuable Resources— Renew for 2022!

It’s not too late to join your neurology colleagues this November 5 through 7 for the fully virtual AAN Fall Conference—registration is still available at AAN.com/Fall.

Year after year, the AAN continues to push to understand how we can better serve our members and their needs as neurology professionals. As our membership continues to grow to over 36,000 global members across 144 countries, your benefits continue to grow as well.

This interactive three-day experience will be accessible from anywhere there’s an internet connection. You will Continued on page 11

11 January 26 Is Deadline to Submit Emerging Science Abstracts

Just to highlight a few: the AAN now has more than 350 courses, exams, and webinars, all created by expert neurology members and volunteers from around the world. Additionally, Neurology® continues to be the most widely

14 Advocates Make Case for Neurology During Legislative Summit

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19 Budhu Named Editor of Neurology IDEAS Online Section


AANnews · November 2021

November 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.

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Read Position Statement on Ethical Perspectives on Costly Drugs

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AAN Position Statement Counsels Neurologists on Use of Social Media

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Emerging Leaders Program Graduate Leads the Way on Patient-centered Education

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: Michael J. O’Brien II Account/Relationship Manager Wolters Kluwer Phone: (978) 578-4514 Email:

Michael.Obrien @wolterskluwer.com

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

The AAN published “Ethical Perspectives on Costly Drugs and Health Care: AAN Position Statement” in the October 4, 2021, online issue of Neurology® at Neurology.org as well as the October 5 print issue. The statement was developed by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.

The AAN published “Use of Social Media in Health Care Opportunities, Challenges, and Ethical Considerations: A Position Statement” in the September 21, 2021, online issue of Neurology® at Neurology.org.

“I found what I learned through the AAN’s Emerging Leaders Program critical to gain knowledge, shape my leadership skills, and navigate the complicated process of creating a new organization,” said 2015 Emerging Leaders Program graduate Augusto A. Miravalle, MD, FAAN, in referring to his impressive accomplishment establishing The Brain Health Center of the Rockies, a nonprofit organization built around empowering individuals to achieve maximal brain health.

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.

News Briefs Section Elections Nominations are now open for leadership positions for many AAN Sections for the 2022–2024 term. Watch for more information to nominate yourself or a colleague. Nominations will be open until December 10.


PRESIDENT'S COLUMN Coming Together in Gratitude After I came to the United States from Israel at age nine, Thanksgiving became my favorite holiday, one that many immigrants adopt upon arrival. Later this month, families across the United States will gather for traditional meals and the custom of counting our blessings and sharing what we are thankful for. It takes a special effort and an intentional choice to find gratitude during this extraordinarily difficult time, arguably the roughest we have encountered to date. Since the pandemic began, 1 in 500 Americans have died, a new milestone reached in mid-September as I write this column. That means that for many families, there will be empty seats around the table, making this holiday season difficult to endure. Children’s wards are filling with COVID-19 admissions and 120,000 children have lost one—or more—primary caregivers, fathers and mothers who will not be present. As many of you have shared with me, the delta variant is still crippling your hospitals and straining intensive care units. Coronavirus is a source of trepidation for parents of students who have returned to school, especially those under the age of 12 who cannot be vaccinated yet. While last Thanksgiving we could look toward vaccines and hold hope for a turnaround, this year we have had to come to grips with the reality of mask mandate refusals, vaccine hesitancy and declinations, and health care worker protests outside some of our very own hospitals. This fourth surge has also brought a critical nursing shortage, a perilous bottleneck placing smaller hospitals on the verge of closure and creating severe understaffing which is driving even more nurses and other medical personnel to leave. For the first time in history, administrators are discussing how to ration care and patients in some parts of the country are being advised to stay home, if they can avoid it, rather than come to backed up emergency rooms. Yet, one of the most extraordinary human traits is the ability to express gratitude in the face of such vicissitudes. This happened at Ochsner when neurologists and residents volunteered to perform the jobs of nursing aides having witnessed their nurses’ struggles. At the Massachusetts General Hospital, a group of physicians, including several neurologists, assembled a team of Spanish-speaking doctors, deploying them as volunteers to help communicate with patients with limited English proficiency admitted with COVID-19 when the interpreter staff was unable to meet the acute rise in inpatient care. Indeed, over the past 18 months, I have heard countless stories of colleagues, friends, and trainees helping each other by covering shifts and on-call duty, serving on the front lines, filling in for those with childcare emergencies or for women who were pregnant. They also checked in on colleagues who fell sick due to COVID, sent care packages, and delivered food and other necessities. In those

acts, they expressed appreciation for each other, and with grace, accepted gratitude. Recent research has confirmed prior Avitzur studies suggesting that gratitude inversely predicts negative affect. In the setting of the pandemic, it appears that individuals who are more grateful may possess more flexible thinking and reactions in threatening situations, and that emotional responses may improve, while negative emotions abate. It is possible that just by expressing gratitude you reinforce a healthier outlook and promote your own well-being. As we embark on our second pandemic Thanksgiving, I want to share my gratitude with all of you. I am thankful to the AAN and all the opportunities it has given me. I am grateful that I was able to travel to Orlando this April, fully vaccinated, to meet with my board of directors, after 15 months of virtual meetings, and introduce them to our new CEO, Mary Post. I am also thankful that we are planning for an in-person Annual Meeting and that I will be able to see many of you at the "Great Neuro Reunion" in Seattle. And more than ever, I appreciate my colleagues and friends who help me see the humor in life, now and then, and keep my spirits up during tough moments. I am thankful to all of you, neurologists who continue to renew your memberships, now comprising 92 percent of the US market share. More than 700 of you are volunteers who have met by Zoom over the last year and a half to ensure that AAN committees remain productive, and to create new programs and initiatives to keep our organization vibrant. I am also grateful to our wonderful staff who keep all those activities humming. I’ve invited a small sample to share their thoughts of gratitude, in their own words. 

Orly Avitzur, MD, MBA, FAAN President, AAN oavitzur@aan.com @OrlyA on Twitter

AANnews  •  November 2021 3


What Members Are Grateful For Professionally, I am very thankful to be a neurologist and address disorders of the brain, the intellectually most fascinating of all organs. Specializing in dementing disorders, I am able to spend time with patients and their families and so I truly get to know them. I also am thankful for the American Academy of Neurology, which indeed is indispensable to its members. Personally, I am blessed by my wife and our wonderful family. —John C. Morris, MD, FAAN I am thankful for my family’s health and harmony, and for a working brain. I am grateful for having chosen a fulfilling career that bestows upon us the immense privilege of the trust and love of our patients. I feel particularly blessed to have a lifelong partner in my dear wife, and to have two wonderful daughters. A final toast to friendship! —Diego R. Torres-Russotto, MD, FAAN I am thankful for the opportunity for lifelong learning as a neurologist, not only from my mentors and fellow attending neurologists, but also from students, residents, and patients and their families. Even though recently retired from active clinical practice, I am grateful for the opportunity to continue my education with virtual Grand Rounds, and all the AAN offerings, including the Neurology Podcast, Neurology Minute, and Neurology Question of the Day. —Gary P. Kaplan, MD, PhD, FAAN

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AANnews  •  November 2021

I am thankful for my AAN colleagues. When I was feeling burned out and unappreciated at my institution, attending an AAN meeting or committee meeting connected me with like-minded colleagues who believe that neurology and medicine is more than a job, it is truly a calling. And that our purpose is to help our colleagues in their careers and to provide better care for our patients. Everything we do is possible because the AAN staff are the highest functioning staff I have ever encountered. The AAN is like a tonic to keep my love of neurology eternally strong. —Janis Miyasaki, MD, FAAN I am grateful that despite the darkness of world events, I am surrounded by people who inspire me, motivate me, and support me to continue the work to make the world a better place. ­—Nicole Rosendale, MD Professionally, I am grateful for a practice that has allowed autonomy and flexibility in my schedule during the pandemic, allowing telemedicine and working from home while my children were home. I am grateful that flexibility continues as my children are back in school because the time of uncertainty we still practice and live in makes flexibility a true commodity. Personally, I am grateful my family has remained healthy. —Jill M. Farmer, DO, MPH I am thankful for my family, friends, and co-workers who have made the last 18 months (yes, I am counting) a time of down-home enjoyment. This change of pace (enforced) will probably be looked at much more favorably as the years go by. —Thomas R. Vidic, MD, FAAN

I thank God for allowing me to provide excellency in medical care to my patients and scientific updates to my colleagues and undergraduate students, based on professional and scientific standards as stated by the current guidelines of the American Academy of Neurology. — Fabricio Ferreira de Oliveira, MD, BBA, MSc, PhD The past year and a half has been difficult for the world but for health care providers, in particular. I’m thankful to work with such compassionate and intelligent people who have continued to provide the highest level of evidencebased care despite the many challenges and barriers they face. They continue to advocate for their patients and for vulnerable people at large. It is an honor for me to count them as friends and colleagues. —Christina Vest, NP I am thankful for my colleagues in public health and infectious disease for being our face of science and evidenced-based action during a time of both pandemic and its resultant public fervor. —Pearce J. Korb, MD, MHPE, FAAN I am thankful for the ability to pursue my passions including sports neurology, education, technology, and tackling health care disparities, and to feel connected to kindred spirits and colleagues all around the country. The fact that I can be thankful on a daily basis for my career and colleagues is not lost on me. Surviving and thriving after Hurricanes Katrina (August 29, 2005) and Ida (August 29, 2021) are blessings and lessons in resilience. —Jose Posas, MD, FAAN


I am thankful for the opportunities for service—to students, patients and their families, and colleagues— and for the ability to contribute to science; but most of all, for friends and family, all of whom have sustained me and enriched my life. —Robert A. Gross, MD, PhD, FAAN

I am grateful to have good health, to have had brilliant and loving parents who guided my life, a loving partner and family who share life’s journey with me, a vibrant and satisfying career, and the honor and privilege to serve humanity every day. —Sarah Jane Hon, DO, FAAN

I am so thankful for all the amazing, positive, and energetic staff and committee members within the AAN. I specifically want to thank the Member Engagement Committee, BrainPAC, Advocacy, and AANnews teams. They work so hard on behalf of all of us AAN members and I am beyond grateful to know and to work with them. Happy Thanksgiving to all! —Melissa W. Ko, MD, FAAN

I am immensely grateful for the clarity the pandemic has brought to my life. The devastation and uncertainty of the pandemic have been catalysts in my journey of reflection and self-discovery. I have redefined my priorities, strengthened my values, and am leaning into fully experiencing and appreciating the present moment. —Andrea C. Wasilewski, MD

I am thankful for continuing to be enthusiastic about my role as a neurologist and teacher, even after 40 years of service to the profession. I work with the best colleagues, both locally and nationally through the AAN, who share my passion for our profession. Teaching my students and residents continues to bring me great joy. I’m so happy that I selected neurology as a career. —Ralph F. Józefowicz, MD, FAAN I am thankful for my wonderful family (including our dogs), great friends, terrific work colleagues, and a profession that I enjoy. —Brett M. Kissela, MD, MS, FAAN I am thankful for the understanding all my patients have shown as we have worked to create a safe environment here in the clinic, and an efficient telemedicine option for them. —James H. Bower, MD, MSc, FAAN

I am particularly grateful that 1) my family is healthy, happy, full of love, and enjoying the glorious Minnesota fall; 2) through support of others, I have the opportunity for exactly the kind of career in cognitive neurology that I have looked forward to, including diversity of roles (clinical care, research, education, and leadership), inclusion and mentoring that promotes growth, and the unique fulfillment that comes with trying to add value to others’ lives. —Vijay K. Ramanan, MD, PhD As a member of the AAN Family, I am grateful for the opportunity to participate in the AAN's continued growth and development, and success during these challenging times. “ —Rodney O. Leacock, MD

In these trying times of a pandemic, I am thankful for the few silver linings: an opportunity to attend conferences and give lectures remotely, my renewed involvement with the AAN, my work as part of the PASC Collaborative where we are setting guidelines for managing Long COVID patients, and the time spent with my children while they attended school remotely. —Svetlana Blitshteyn, MD

I am grateful for my 2018–2019 Transforming Leaders Program colleagues. I experienced personal growth with and through them. And it never fails that when I’m feeling beat and running on empty, one of them will text or email an inspiring shout-out that helps me carry on. Friends for life. —Gregory P. Hanes, MD Despite many hardships and losses the past year and a half, I am grateful for my amazing life. My wonderful family, friends, and colleagues. My health, my financial security, and my opportunities. I still enjoy working with patients and doing neurology. I enjoy working with the AAN and the amazing staff they have. Life is good and I am excited for the future. —Elaine C. Jones, MD, FAAN

The phrase ‘life is a gift’ is perceived so vividly during this pandemic. I am thankful for the science that made vaccine development possible in an incredibly short timeline. I am grateful for every person in health care worldwide who fights to save lives and strives to end this pandemic. More than ever, I enjoy and appreciate the little things in life. —Khatuna Gurgenashvili, MD

AANnews  •  November 2021 5


What Members Are Grateful For I am extremely thankful to you for being involved in the Digital Strategy Subcommittee, as an overseas member. I could attend the introductory meeting held recently and briefly learned about all members. The Annual Meeting I could not attend as time difference between US and India is a big challenge to overcome but I am hopeful to do justice to my inclusion in the subcommittee in coming months. — Nirmal Surya, MD, DNB (Neuro) FIAN, MNAMS, FRCP (London)

I am most thankful for my family and friends. I am also thankful for our health and wellness during these challenging times. I am thankful for the contribution I may offer to supporting, helping, and healing my patients, family, friends, and neighbors. I am lastly very thankful that technology was available to provide care in a virtual world, entertainment through endless streaming options, and social contact when physical presence was not possible. —Charlene Gamaldo, MD, FAAN

On a professional level, I am thankful for the opportunity to care for my patients and for the trust that my patients have extended to me by letting me be part of their care team. On a personal level, I’m thankful for having loving and understanding wife, daughter, sibling, and parents, who have been by my side as my pillars of support through the thick and thin. —Anil Neelakantan, MD, FAAN

Personally, I am grateful that we were able to virtually celebrate my parents’ 50th wedding anniversary this year and that we have more family moving closer to us, which truly has been a joy. Professionally, I am grateful for my patients, my supportive colleagues, the ability to work on wellness more intensively at a local level, a job that allows me to fulfill a calling (even with all of its challenges), and, of course, the AAN family! —Jennifer R. Molano, MD, FAAN

My junior colleagues and mentees in both Africa and the US whose resiliency and determination to provide high-quality care and conduct excellent research remains undeterred regardless of the challenges they face daily. I am in awe of their grit and grace. They are my heroes. — Gretchen L. Birbeck, MD, MPH, DTMH, FAAN

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AANnews  •  November 2021

COVID has given me a profound appreciation for people with whom I work, who have shown so many acts of kindness that I began to chronicle them in a journal. One example from last year is my colleague, Dr. Leep Lunderfund, who delivered a phenomenal home-cooked dinner along with a colorful picture to me when I was unable to go home for the holiday and had to work. I am thankful to her and to the support of my Mayo team. —Eseosa Ighodaro, MD, PhD

I am grateful for one love, two children, two good friends, a beautiful afternoon, a fate to study medicine, the appreciation of the insignificant, and for what I am destined to suffer. —Maria Kinali, MD, FAAN I am thankful for the opportunity to practice neurology at a high level and pass on to future generations through residency training the skills, concepts, and clinical reasoning for their patients. I have been blessed with wonderful, talented, and humble colleagues. I am grateful for the opportunity to participate in the AAN committees and do the good work of the organization. —Allen J. Aksamit, Jr., MD, FAAN I am thankful for every single breath and heartbeat, health, my family and loved ones who love and support me, my job, wonderful colleagues and friends, being able to help others, being a part of the AAN, and countless blessings! —Amtul Farheen, MD, FAAN I am grateful to be living in this time of medical advancement. Just over three years ago, I was diagnosed with an extremely challenging medical condition in an early stage and was able to tackle it aggressively and proactively. Currently, I feel great and despite COVID, have been able to return to work, participate in the MEC and other AAN initiatives, start travelling, and most importantly, been able to enjoy my family. I truly appreciate all of the support, good vibes, and prayers from my family, friends, and colleagues which have really helped me in this journey. —Bryan Soronson, CRA, FACMPE, MPA


I am grateful for the love and support of my family, friends, and colleagues during my career in medicine, and specifically neurology. It was extremely important to me, as I entered a field and profession at a time when women were a distinct minority, but I was accepted as a physician and was able to pursue my goals alongside my fellow practitioners. — Sandra F. Olson, MD, FAAN, AAN President 2003–2005 I am thankful for the rainbows AND the clouds which teach me that nothing lasts forever, good or bad. Therefore, I am especially thankful for the good times in my life because they allow me to stay present, practice mindfulness, and to center my attention on appreciation, knowing that “This too shall pass.” —Belinda A. Savage-Edwards, MD, FAAN I am grateful for the people in my life who have showed me the true meaning of friendship and selfless love. —Jerome H. Chin, MD, PhD, MPH, FAAN

I’m grateful for the privilege of teaching neurology every day. Every once in a while, when I’m with a group of learners diving into the minutiae of clinical neurology, I have one of those “Pinch me, I must be dreaming” moments that I get to do this with my life! —Jeffrey J. Dewey, MD, MHS

I am thankful for the compassion, professionalism, and resilience of my fellow medical providers during these unprecedented times. I am thankful for the essential workers: grocery store workers, waste collectors, firefighters, EMS, law enforcement, and all of those who deliver our packages/mail. I am thankful for those who have received the COVID vaccination, for wearing a mask, and respecting social distancing. Lastly, I am so thankful for time spent with family. —Nanette Paredes PA-C 

I am thankful for my wife and all who are intimately involved in raising children. This pandemic has highlighted the disproportionate degree of "home" duties that are unfairly tasked to women. As a man, I apologize and am thankful for a woman's love and sacrifice. I am thankful for my children and all children. Although my kids don't always act like angels, they truly are heavenly gifts. I'm thankful for the opportunity to be more involved as a family man. —Roland Hamilton, Jr., MD

Simply Thankful I am thankful for family, for colleagues and staff I am grateful for their wisdom, support and contagious laughs The effects of the pandemic have been arduous, stressful and tough But I am thankful for persevering, even when times were overwhelmingly rough

Personally, I am grateful I can go for a swim at the beach and watch a beautiful sunset every day of the week. Professionally, I am thankful for all the friends I have made volunteering with the AAN. —Beau Nakamoto, MD, PhD, MBA, FAAN

I am thankful for the Academy, for its resources and tremendous zeal Your efforts throughout the pandemic were extraordinary and real I am thankful for my patients, and for advances in technology

I am grateful for my wonderful parents who provided me love, support, and wings to fly and meet my dreams; to mentors for helping me build an academic career; to my family for their enduring faith in me; and to life for presenting me with so many amazing opportunities to help others. —Shilpa Chitnis, MD, PhD, FAAN, FANA

I am thankful to be a part of the incredible field of neurology —Lucretia Long, APRN-CNP, FAES

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What Staff Are Grateful For Access to health care for my family. —Rachel Anderson

I am thankful for the talented and committed AAN members and staff I get to work with each day―and the joy they bring each other in taking on meaningful work that is full of purpose. —Angela M. Babb, MS, CAE, APR I am thankful for science and the role it plays in keeping my family safe and healthy, and to work for an organization that prioritizes the same. —Lee Ann Kleffman I am grateful for my family who has supported me throughout my professional career. I am grateful for the AAN and the opportunity to lead alongside exceptional members and talented staff on a mission that engages my heart every day. —CEO Mary E. Post, MBA, CAE I’m thankful I’ve learned to value relationships over ego. —Sharon Quimby Thankfulness for the simple things in life has been a focus for me lately, as they can be easy to overlook. A warm meal, my cuddly dogs, fall weather, gracious family and friends, second chances, and chocolate. Definitely grateful for chocolate. —Erica Slack

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AANnews  •  November 2021

I’m thankful for hopefulness and human resilience. Life isn’t without challenges, and we all need to lean on each other to get through the ups and downs. —Martha Boyle I am grateful for a beautiful sunny fall day, a terrific book, snuggling with my dog, but most of all, my health, and the health of my family. —Tina DiRienzo For amazing family, friends and coworkers, a job that makes me smile, and for people in my life who motivate and encourage me every day. —Lynee Koester I am thankful for my supportive and amazing husband and best friend of 24 years; our three amazing, smart, and talented children; and all of our friends, family, and coworkers that make each day an adventure. —Susan Corcoran I am thankful for the amazing friends and family in my life who have always supported each other, through good times and bad. —Tasha Ostendorf

I am thankful for being able to work with so many dedicated and passionate staff and member volunteers who do their best to help make the Academy indispensable to its members— we do not always succeed in that vision, but it’s the strive and the drive for which I am grateful. —Chris Keran, PRC I am thankful for my encouraging and supportive partner, family, friends, and colleagues; I’m lucky to be surrounded by a great community. —Andrea Rahkola I have gratitude for many things, my family, my health and working for an organization that inspires me to work with integrity, be my best, and one that has a great impact on our members and the patients they serve. —Deanna Ekholm, SPHR I am thankful for the gift of health that allows me to experience joy and laughter while creating wonderful memories with my family, my friends, and my AAN coworkers. —Denise Shouse, CDMP I am thankful for my family, friends, and colleagues who allow me to enjoy life and in return the ability to support them in all that they do that brings joy and success into their lives. —Arnel Rillo


I am thankful for the strong women in my life who have always empowered me to be the best version of myself. —Allison Perales I am thankful for the opportunity to spend the holidays with family again. After having to stay away from loved ones last year, it will be so much more meaningful this year to celebrate with parents, siblings, aunts, uncles, nieces, and nephews.

I am thankful for my health. I am especially grateful that our community is talking more about mental health and supporting those with mental health challenges.

I am thankful for health and wellness, staying connected and being curious and creative. Wishing all the best for family, friends, and colleagues near and far.

—Michelle Maxwell

—Tabitha Sanbower

Grateful for family, friends, pets, coworkers, parks/ nature, vaccines, good food, access to clean water, and excellent health care.

I am grateful for my family and friends who are my rock. I am thankful for the scientists who are working hard on developing vaccines that are allowing us to spend precious time with our loved ones.

—Carolyn Cahill

—Amanda Becker

—Michelle Uher, CAE, APR

CESC: 20 NeuroByte_Online Learning Ad—Half Page Horizontal> AN Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C

AAN ONLINE LEARNING Browse a variety of online CME, self-assessment, and other learning activities to suit your wide-ranging interests and learning styles.

AAN.com/learn


BOARD SPOTLIGHT Meet Your New Board Member: Maisha T. Robinson, MD, MSHPM, FAAN Maisha T. Robinson, MD, MSHPM, FAAN, is an assistant professor in the department of neurology at Mayo Clinic in Florida, with a joint appointment in the department of family medicine. Upon joining the staff of Mayo Clinic, she established the clinic’s first neuropalliative care program and she currently serves as the medical director of palliative medicine and as the program director for the Palliative Medicine Fellowship.

How did you first get involved as a volunteer on committees/subcommittees and what moved you to participate? I was fortunate enough to be selected as a participant in the inaugural Emerging Leaders Forum in 2012 and at the time of completion of that program, I was appointed to the Meeting Management Committee and became involved in the Medical Student Diversity Program. At the time that I applied for the Emerging Leaders Forum, I was unsure about the value of my Academy membership. That program was pivotal in my understanding of the Academy’s many efforts on behalf of its members. I was so appreciative of the investment that the Academy made in me and I wanted to offer a good return on that investment!

What experiences and viewpoints do you bring to this role? It was an honor for me to be appointed as the chair of the Member Engagement Committee and to subsequently join the Board of Directors. This speaks to the value that the Academy places on optimizing the member experience. It’s important to me to be able to be an advocate for our members among the leaders of the Academy.

PODCAST

Why did you wish to be on the Board of Directors?

Robinson

Over the past nine years I’ve served in a wide variety of roles within the Academy from the chair of the Medical Student Diversity Subcommittee to the vice chair of the Meeting Management Committee, to the Nominating Committee, Leadership Development Committee, Diversity Leadership Subcommittee, the Editorial Board of Brain & Life®, as well as a number of other committees, subcommittees, work groups, and task forces. This has allowed me to better understand the breadth and depth of the AAN. In addition, I offer a perspective cultivated by my experience as an earlier career and racially diverse neurologist.

In your view, how does the AAN benefit the field of neurology most? The AAN is an invaluable proponent of neurologists’ needs and concerns regarding clinical practice, research agendas, and career development. It has also become instrumental in addressing pipeline issues, leadership development, and the neurologic health of the community. 

Neurology ® Podcast:

20 Minutes Pack a Punch! Subscribe and download the latest podcast at Neurology.org/podcast

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AANnews  •  November 2021


EVENTS January 26 Is Deadline to Submit Emerging Science Abstracts The AAN seeks previously unpublished research in which JANUARY key aspects must have been completed after the October 11 abstract submission deadline that showcases timely, significant, and innovative content warranting expedited presentation for the Emerging Science Program for the 2022 AAN Annual Meeting in Seattle. Visit AAN.com/22Abstracts to learn more and to submit by the January 26 deadline. For questions, contact Erin Jackson at science@aan.com. 

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There’s Still Time to Register for the November 5–7 Virtual Fall Conference  continued from cover receive timely updates on the hottest topics in neurology, real-world issues in practice management, the most innovative science, valuable networking opportunities, a half-day course on anti-amyloid therapy, exclusive leadership programming, a Wellness Challenge to see who takes the most steps during the conference, and up to 42.5 CME credits to meet your end-of-year requirements. Registration includes access to the live virtual event, Q&A with faculty, session recordings, and program materials through Sunday, November 21—or upgrade to Gold registration for extended access to content.

Can’t Make It to the Live Virtual Event? Get It on Demand! Look for Fall Conference On Demand coming available this November 22 in the Online Learning Center. With Fall Conference On Demand, you’ll get access to recorded sessions, content, and syllabi from the live virtual event, plus extended access through September 30, 2022. 

NEUROCRITICAL CARE OCTOBER 2021, VOL 27, NO 5

In Unprecedented Times, Rely on Continuum Join your colleagues who depend on Continuum® and Continuum® Audio to stay informed on the latest in patient care. AAN members get both for only $399!

ContinuumJournal.com


PRACTICE Registry Users Encouraged to Apply for QI Pioneers Program The AAN seeks Axon Registry ® users to participate in the QI Pioneers program, designed to help them succeed in improving performance on registry measures. Selected participants receive hands-on training, guidance from quality improvement experts, and the opportunity to network with like-minded peers in health care. The deadline to apply is December 14.

Eligibility

“Participating in the AAN QI Pioneer Program helped the Minneapolis Clinic of Neurology to improve and sustain the rate of Dementia Functional Assessment over the course of 12 months. Using the Axon Registry to collect data, we saw a 44.59-percent improvement from December 2018 to December 2019.”

Practices must be currently participating in the Axon Registry and be interested in improving performance on one registry measure over a 12-month period. QI Pioneer applicants are asked to identify a physician/clinician champion and staff leader at their practice who will work together to implement quality improvement drivers, monitor progress, and leverage resources to drive change in their practice. The physician/clinician champion must be an AAN member.

What to Expect

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Brain & Life® magazine and website is the only single source for trustworthy education on all neurologic conditions and brain health—and it is a member benefit to you for your patients. US AAN Members: Sign up to receive bimonthly print issues for your office at BeGreen@WasteFreeMail.com and invite your patients to subscribe for FREE.

BrainandLife.org


ADVOCACY Read Position Statement on Ethical Perspectives on Costly Drugs The AAN published “Ethical Perspectives on Costly Drugs and Health Care: AAN Position Statement” in the October 4, 2021, online issue of Neurology ® at Neurology.org as well as the October 5 print issue. The statement was developed by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society. “High drug prices have created significant challenges for patients and their physicians, with dramatic price increases not just limited to specialty drugs but also to generic ones,” said position statement author Amy Y. Tsou, MD, MSc, of ECRI in Plymouth Meeting, PA. “This position statement examines ethical concerns surrounding high drug prices and how they can impact patient care in many ways, including limiting access to treatment and posing direct challenges for distributive justice—the fair distribution of benefits and burdens across society.”

drugs to secure lower cost options for some drugs. Another possibility would be Tsou to allow Medicare to negotiate drug prices, a strategy that has broad support among Americans. Benchmarking Medicare prices against the prices that other countries pay could be an option. Also, setting drug prices based on how much benefit it provides, an approach known as value-based pricing, could be another strategy to pursue.

The position statement notes that high drug costs limit treatment access not only for people without insurance, but also for people with high out-of-pocket costs or coverage that doesn’t include high-cost treatments. Dramatic job losses during the COVID-19 pandemic and the resulting loss of insurance have further exacerbated existing disparities in access to health care.

“People with complex, chronic conditions like Parkinson’s disease, epilepsy, and migraine often need specialty drugs that require special handling or administration, and some neurologic drugs, such as those for multiple sclerosis, can be particularly expensive,” said AAN President Orly Avitzur, MD, MBA, FAAN. “Drug pricing is a priority for the American Academy of Neurology. We support policy solutions that would allow for price negotiation and transparency to ensure that prescription medications are accessible for patients with complex, chronic neurologic conditions.”

The statement notes that given financial concerns, people with and without insurance may choose to ration their own medications to save money. Such rationing can have serious risks, including death. It also discusses how drugs are currently priced in the US. Specifically, the statement notes that drugs are priced higher in the US compared to other countries because pharmaceutical companies have had important key protections from competition and negotiation.

Tsou said, “Exacerbation of existing health care disparities by the COVID-19 pandemic has highlighted the moral imperative to address these inequities, but also the monumental scale of undertaking such a challenge.” 

The position statement describes possible policy solutions that may address high drug costs. For example, the FDA has worked toward speeding up approval of generic equivalent

AANnews  •  November 2021 13


ADVOCACY Advocates Make Case for Neurology During Legislative Summit On September 29, 93 AAN members from 44 states connected with their senators and representatives for the Academy’s third Legislative Summit. Conducted virtually, the advocates pressed 188 lawmakers on three major issues: Support for the neurology workforce Permanent expansion of telehealth access Protection of Medicare patient access to care Joohi Jimenez Shahed, MD, hosted a Neurology Minute® podcast to explain what the summit is and summarize the AAN’s position on these issues. Rep. Terri Sewell (D-AL) held a town hall with the AAN advocates to talk about her efforts in addressing GME and workforce issues. The Legislative Summit resulted in 1.5 million impressions on social media using #AANadvocacy and 230 Action Alert email participants. In addition, attendees at the summit accounted for more than $64,000 in BrainPAC contributions towards our efforts over the course of 2021. Thank you to all who attended and made this event a success! 

14

AANnews  •  November 2021


AANnews  •  November 2021 15


ADVOCACY AAN Position Statement Counsels Neurologists on Use of Social Media The AAN published “Use of Social Media in Health Care Opportunities, Challenges, and Ethical Considerations: A Position Statement” in the September 21, 2021, online issue of Neurology ® at Neurology.org. The authors explain, “The AAN developed this position statement to review in-depth how social media use has transformed clinical practice—with a particular focus on neurologic practice—and, by exploring the relevant principles in the CPC [Code of Professional Conduct], to provide an ethical framework for neurology professionals and trainees to consider when engaging in social media. This statement complements the CPC; it is not a replacement for the AAN website’s Code of Conduct, Privacy Policy, or Terms of Service.” The position statement examines how social media has enriched the medical profession through information exchange, distribution, networking, education, and research. It weighs the positive aspects of patient education, counseling, and treatment against the challenges of dealing with and avoiding misinformation. Professional guidance is given on how to conduct oneself when using social media, maintaining boundaries and privacy, and separating clinicians’ private versus professional profiles. The authors conclude “…while increasing use of social media has expanded the availability and reach of medical information ESC: 21FC Registration#3 Ad—Half Page Horizontal> AN and social interactions, it also carries important ethical Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C Clinicians must adhere to core ethical principles obligations. and norms of professional behavior that have guided patient

care for centuries, while updating and extending these principles to the novel domain of social media. Clinicians should challenge themselves to expand their traditional roles beyond the clinic or hospital setting and traditional ways of publishing. By appropriately using social media, clinicians can more broadly impact public health and medical literacy—an important service to provide at a time when information (and misinformation) is shared so extensively and rapidly. Timing and context of social media use affect how it is perceived; and yet, once something is publicized, it can be reposted, shared, or disseminated at any future time and in different contexts. “As social media use grows, clinicians should aim to avoid moral pitfalls and public misrepresentation by aligning their professional social media communications with established norms of professional conduct. Interaction with social media has become a critical element in both individual and professional life, and current clinicians and trainees need to be educated in its use. Despite its many challenges, social media provides opportunities to greatly enhance our ability to improve the lives of our patients and to enrich our professional lives. The growing importance of social media in health care has accelerated dramatically during the COVID-19 pandemic and is likely to continue for years to come.” 

Virtual 2021 November 5–7, 2021

Register Today! Valuable CME. Expert Faculty. Improved Patient Care.

AAN.com/Fall


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.

Advocacy with FDA, CMS, CDC, and Congress Produces Results As previously requested by the AAN, the Food and Drug Administration authorized a third dose of Pfizer Inc.-BioNTech SE's COVID-19 vaccine. Additionally, the Centers for Disease Control and Prevention recommended the booster shots for health care workers, teachers and others at occupational risk for COVID-19. The CDC decision broke with an independent advisory group that recommended extra doses for older adults, people in nursing homes and those with underlying medical conditions, but not frontline workers. On September 21, the AAN, along with the American Geriatric Society and the Society for Nuclear Medicine and Molecular Imaging met with officials from the Coverage and Analysis Group at CMS to discuss the importance of beta amyloid PET scans for the diagnosis and treatment of Alzheimer’s disease. This meeting was held in response to the letter these three specialty societies sent to CMS in July after the controversial approval of aducanumab on the same topic. Officials from CMS were grateful for the commentary from AAN experts and expressed interest in continued contact with AAN members as they make their decisions regarding beta amyloid PET scans and amyloid therapies, such as aducanumab, more broadly.

The AAN published a position statement titled "Ethical Perspectives on Costly Drugs and Health Care", which examines ethical concerns surrounding high drug prices and how they can impact patient care, including limiting access to treatment and posing direct challenges for distributive justice—the fair distribution of benefits and burdens across society. Congress passed a continuing resolution (CR) to keep the federal government open past the end of the fiscal year on September 31. The measure will keep federal government departments and agencies operating under current funding levels until December 3, 2021. The CR also extends the availability of funds for multiyear NIH grants that were obligated in FY 2016 and were interrupted due to COVID-19. The Senate has also agreed to raise the debt ceiling through December 3 to avoid default on US financial obligations. Congress is seeking a path forward to reconcile differences within the Democratic caucus on the bipartisan infrastructure bill and the Build Back Better Act, a proposed reconciliation package which only requires a simple majority and bypasses the filibuster. The legislation includes multiple health care provisions, such as Medicare expansion and lowering prescription drug prices. 

AANnews  •  November 2021 17


EDUCATION Emerging Leaders Program Graduate Leads the Way on Patient-centered Education “I found what I learned through the AAN’s Emerging Leaders Program critical to gain knowledge, shape my leadership skills, and navigate the complicated process of creating a new organization,” said 2015 Emerging Leaders Program graduate Augusto A. Miravalle, MD, FAAN, in referring to his impressive accomplishment establishing The Brain Health Center of the Rockies, a nonprofit organization built around empowering individuals to achieve maximal brain health. The idea for the center was inspired by comments from his patients and conversations with his wife, Kathy, who worked as a management consultant for a European multinational corporation. Her job included explaining complex topics to large groups of individuals from different cultural backgrounds, often with minimal or no knowledge on the subject matter. Kathy’s leadership skills, combined with Augusto’s background in medical education, gave the couple the perfect mix of foundational tools to turn their conversations about a nonprofit organization with a goal of providing patient-centered education on brain health into action. “Medical education, health care literacy, and counseling are essential parts of health care delivery, particularly when it comes to complex concepts like the ones involved in understanding brain health,” explained Miravalle. “During my academic career, I was involved in medical education, from curriculum development to implementation of educational activities for learners at various levels of training.” Miravalle is quick to point out that The Brain Health Center’s educational activities are novel, emerging from a deep understanding of patient-centered needs, combined with effective experiential activities intended to promote lifelong learning. Participants learn innovative and sustainable changes across a broad domain, from physical and psychological health to nutritional and wellness best practices, providing them with the information necessary to actively participate in medical decision-making. Participants are also connected with leading professionals to help facilitate a multidisciplinary approach of care and provide the support they need. “In order to create a patient-centered organization, you need to be able to identify current gaps, understand patients’ needs, and, more importantly, utilize well-established principles of medical education and apply them to patient education,” said Miravalle. “As an example, one of my dear mentors, Ralph Józefowicz, MD, FAAN, taught me that ‘planned redundancy’ is one of the most effective methods to teach complex medical processes. During the Brain Health Center’s five-week Brain Health Program, patients are exposed to information and knowledge in a way that is sequential, gradual, and certainly follows the principle of repetition. In that way, we allow patients to conceptualize these complex topics and enhance learning as a result of repetition of key points, illustrations, and definitions.” Like the world around it, the Brain Health Center transitioned its in-person programming to a virtual platform throughout the 2020 and 2021 COVID-19 pandemic. “During the latter half of 2020, feedback from participants was extremely positive about this transition, and many patients have enjoyed not having to

18

AANnews  •  November 2021

commute every week to class,” he said. Miravalle The online format has also fostered larger outreach. “We no longer simply serve northern Colorado and southern Wyoming. While most of our patients are still primarily local, we have also had MS patients from all corners of the country and, to date, these programs have been attended by over 200 people with MS and their caregivers.” The Brain Health Center also offers larger conferences for patients and providers with a total combined audience of over 500 individuals, and it recently partnered with faculty at the Colorado State University’s Music Therapy, Health, and Exercise Science, and the Sensorimotor and Neuroimaging Laboratory departments, as well as the university’s Anschutz Department of Neurology, to develop exciting joint projects aimed at furthering the Brain Health Center’s mission. “But perhaps the most important outcome of this project was personal,” said Miravalle. “As we all know, burnout is a serious problem among health care providers, particularly in neurology. One of the underpinning factors associated with burnout is a misalignment between one’s professional and personal life—the so-called work-life balance. Being able to work side-by-side with my wife allowed me to truly integrate my work life with my personal life and blend it all together so one aspect doesn’t take over and become the only thing we do with our time. It was also enlightening to learn from her experience in corporate work and apply those principles to patient education, a process that requires creativity, flexibility, and, certainly, the ability to diversify your network—all skills that were discussed during the Emerging Leaders Program.” To learn more about the AAN Emerging Leaders Program, visit AAN.com/ELP.  Thank you to the organizations supporting this program in part:

Alexion Pharmaceuticals, Inc. Supernus Pharmaceuticals, Inc.


MEMBERSHIP

Budhu Named Editor of Neurology IDEAS Online Section Inclusion is the reason the AAN was founded. To be an organization that is the home for all neurologists. It is what makes us stronger. In 2020, the AAN Board of Directors adopted a new goal to be a fully inclusive, deliberately diverse, and anti-racist organization. We also expanded our core values of Inclusion, Diversity and Equity to now include, Anti-racism, and Social Justice, otherwise known as IDEAS. We are working hard to achieve this new goal and demonstrate these expanded values through an actionable roadmap approved by the Board. Members should look for updates in AANnews to follow our progress. Joshua A. Budhu, MD, MS, has been named editor of the Neurology ® journals’ IDEAS online section. He will begin his term on December 1, 2021. Budhu, a neuro-oncology fellow at Massachusetts General Hospital and a Commonwealth Fund Fellow in Minority Health Policy at Harvard T.H. Chan School of Public Health, is an advocate for health equity and inclusion in medicine. He teaches Harvard medical students, fellows, and residents and has served in multiple leadership positions at Harvard, including as community outreach officer for the Resident & Fellows Committee Center for Diversity and Inclusion and as chief neurology resident. He has also served on national committees focusing on diversity and inclusion through the American Academy of Neurology and the Society for Neuro-Oncology. “I am excited to bring my experience and vision to the AAN and Neurology” said Budhu. “Throughout my career, I have focused on serving the underserved. Drawing on my personal lived experiences, education, and training to provide a unique perspective and vision to the journal, I hope to promote awareness of health care disparities and to advocate for change, both on the community and national levels.”

Budhu of experiences lived within the realm of IDEAS with the goal of informing and enlightening our community on these critical issues. Some Voices: Lived Experiences accounts are written by the journal’s IDEAS editor; others are written by solicited and unsolicited contributors.

Budhu himself made a contribution to the section in June 2020: "COVID-19: A grim reminder of my roots." To learn more, visit Neurology.org/ideas-editor. 

Thank You!

We are grateful for the contributions of our founding editors, who have created an essential resource for continued discussion of IDEAS research, lived experiences, and values.

Readers can expect to see articles from the Neurology journals promoting IDEAS in medicine, podcast interviews, blogs, conferences, job postings, events, CME opportunities, training courses, lectures, and other activities related to IDEAS highlighted in the section. Budhu will also be soliciting contributions to the popular ‘Voices: Lived Experiences’ feature in the section. Voices: Lived Experiences features short first-person accounts

Jeffrey C. McClean II, MD, FAAN Nicte I. Mejia, MD, MPH, FAAN Nicole Rosendale, MD

McClean

Mejia

Rosendale

New Synapse Mobile App Now Available A new mobile app for SynapseSM Online Communities is now available to make connecting with your neurology colleagues from around the globe easier than ever! From the convenience of a mobile device, AAN members can now engage in rich and timely discussions with neurology professionals from more

than 140 countries to share ideas and concerns on the latest health care topics and to help shape the future of neurology.

subspecialty areas and AAN members are encouraged to join as many sections as they like to engage with others in their area(s) of interest.

Synapse is the communication platform for the AAN’s 41 sections and open communities and is an exclusive benefit of AAN membership. AAN Sections represent a wide range of

To learn more about the mobile app and how you can get started downloading and using it, visit synapse.aan.com/faq. 

AANnews  •  November 2021 19


MEMBERSHIP AAN Membership Offers Access to Valuable Resources— Renew for 2022!  continued from page 1 Not only does AAN membership offer you essential education through an abundance of convenient online and in-person offerings, it also carefully curates scientific resources and the most trusted clinical guidelines to help you stay abreast of the latest treatment advances for your neurology patients.

read and highly cited peer-reviewed neurology journal with an impact factor of 9.91. And let’s not forget about the Neurology Question of the Day app, offering members a quick and fun way to assess their knowledge and earn CME credits.

Community Education

Professional Growth

Practice Management

Advocacy

Wellness Research

AAN.com/Membership

YOUR SOURCE FOR SUCCESS AAN in the News “Flavonoids” were on everyone’s lips in July, and hopefully on their plates as well. A Neurology ® study suggesting a diet high in these compounds may slow cognitive decline was covered by the New York Times, CNN, Yahoo! and hundreds of broadcast outlets around the country. More food for thought: Another Neurology study connecting the Mediterranean diet to brain health was covered by CNN. And a new position statement from the AAN on ethical considerations in dementia care was covered by MedPage Today and Healio. 

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AANnews  •  November 2021

The AAN also recognizes that our members’ needs go beyond education and science, which is why we continue to grow opportunities for personal development through leadership programs and volunteering, wellness resources and programs, and various ways to network and connect with other members like SynapseSM Online Communities! AAN membership provides access to valuable resources, programs, and opportunities to help you bolster your patient care and professional success. Renew for 2022 at AAN.com/dues or for more information, contact AAN Member Services at memberservices@aan.com, (800) 879-1960, or (612) 928-6000 (international). 


Avitzur Hosts Video Series Featuring Neurologists and Patients The AAN is producing a new series of videos hosted by President Orly Avitzur, MD, MBA, FAAN, centered on the personal aspects of neurologic care. Neurologists and their patients discuss the value of connection, patient care, and brain health. In the first episode, “Brain Health and Stroke,” Avitzur has a conversation with Natalia S. Rost, MD, MPH, FAHA, FAAN, chair of the AAN Science Committee, and Jessica Diaz, whom Rost treated for stroke. Diaz shares her stroke story and Rost provides a medical synopsis. Diaz, who has since become an advocate for women’s brain health, tells how the care she received from Rost inspired her. To view this episode, visit Youtube.com/aanchannel. 

AMERICAN BRAIN FOUNDATION 2022 Grants Aim to Promote Equal Access to Diagnosis and Treatments Brain disease disproportionately affects marginalized populations in the US, including Black, Latino, Native American, LGBTQ+, people in lower socioeconomic groups, and individuals living in underserved communities. These same populations often experience a lack of basic access to health care and neurologic care, as well as other types of severe health disparities. They are often underrepresented in brain disease research careers in medicine and neurologic research. In response, the American Brain Foundation, in collaboration with the AAN, has established two new funding opportunities for 2022 designed to promote equal access to diagnosis and treatments. Recipients will be announced in January. Next Generation Research Grant in Neurodisparities This $150,000 scholarship supports career development of clinician-scientists with emerging expertise in neurologic health care disparities by fostering research that produces an understanding of how social determinants and bioscience influence brain health, the effect of disparities on neurologic health, potential interventions to address health disparities, and how to integrate the impact of social determinants in clinical practice.

Seed Grant Funding to Promote Diversity, Equity, and Inclusion in Autism Research This pilot grant provides up to $60,000 in seed funds for research to increase knowledge about autism spectrum disorder in populations that have been excluded from or underrepresented in research. The Foundation hopes to offer these grants again in 2023. Visit AmericanBrainFoundation.org/health-disparities to learn more about these and other research grant opportunities as well as how you can support the Foundation’s efforts in creating more opportunities for researchers to help lead the way to cures. 

AANnews  •  November 2021 21


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

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

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

PATIENTS TREATED

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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

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*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


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