THE ANNUAL MEETING NEWS DAILY
Saturday, May 4, 2019
LATEST TRANSLATIONAL RESEARCH UNVEILED IN TODAY’S HOT TOPICS PLENARY Make your way to the Terrace Ballroom from 4:15 p.m. to 5:30 p.m. today to hear four outstanding speakers summarize their trailblazing translational research and describe the clinical implications of the results. This session will be moderated by AAN Science Committee Member Eric Klawiter, MD, FAAN, of Massachusetts General Hospital, Boston, MA, and will use Audience Response, which allows attendees to submit questions that the moderator will weave into the discussion. To participate in Audience Response, visit AAN.cnf.io or connect via the AAN Conferences App.
Klawiter
Continued on page 40 u
Axon Registry Experts Vote on Board on Hand to Answer Nominees at Today’s Your Questions in Philly Business Meeting
Have you ever wondered what the AAN’s Axon Registry ® can do for your practice? To learn more and get hands-on experience with this free AAN product for US members that will help unlock your practice data, stop by the Axon Registry booth located in the Broad Street atrium. The booth will have opportunities to test the Axon Registry dashboard, talk with registry staff, and get all your questions answered. The Axon Registry, a qualityimprovement and qualified clinical data registry, is your solution to fulfilling multiple regulatory requirements. It can also be used by your practice to meet Merit-based Incentive Payment System (MIPS) reporting requirements and certain Continued on page 37 u
Members are encouraged to attend the AAN’s 2019 Business Meeting being held today at 3:00 p.m. in Room 204 AB of the Philadelphia Convention Center, to participate in this election of the slate of nominees for AAN officer and director positions for the 2019–2021 term. The meeting will include reports from officers on the accomplishments of the AAN during 2018 and a review of the organizations’ fiscal health. Continued on page 22 u
Inside
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2019 AAN Award Winners Announced
Calls for 31 AAN Uniformity of Brain
Death Determination
Inspiring and 33 Today’s Innovative New Talk to Explore Bionics
for These 33 Look Opportunities for ‘Continuing the Conversation’ All Week Long
In Multiple
Sclerosis—
GREY MATTERS, TOO
FIND OUT WHY
Booth 2300
© 2019 Celgene Corporation All rights reserved. 03/19 US-CLG-19-0291
Saturday, May 4 Cover Latest Translational Research Unveiled in Today’s Hot Topics Plenary
Axon Registry Experts on Hand to Answer Your Questions in Philly
Vote on Board Nominees at Today’s Business Meeting
4 6
Welcome to the Annual Meeting! 2019 AAN Award Winners Announced
28 Visit the Networking and Innovation
The Vision of the AAN is to be indispensable to our members.
28 New Academic Neurology Room
The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction.
Space to Discover the AAN’s Robust eLearning Opportunities Offers Hub for Resources, Team Building, More
29 What Excited You Today at #AANAM? 31 AAN Calls for Uniformity of Brain Death Determination
33 Today’s Inspiring and Innovative New Talk to Explore Bionics
16 Today’s Experiential Learning
33 Look for These Opportunities
17 Mobile App Makes Planning Your
37 See What the Synapse Buzz Is About
23 DeAngelis to Receive President’s Award
38 What Are Your Colleagues Saying? 40 Boxed Lunch Menu 46 Learn About Job Openings, Career
Area Highlights
Week in Philly Easy
24 Build and Expand Your Leadership Potential Throughout the Week
26 Spanish-language Programs Cover Wide Range of Topics
for ‘Continuing the Conversation’ All Week Long at Experience the AAN Area
Center Resources—and Receive a Free Gift!
Daily Reminders Education Program Syllabi and Slides Available Online Only
Contact Information: 201 Chicago Avenue Minneapolis, MN 55415 USA Phone: (800) 879-1960 (Toll Free) or (612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com AAN Chief Executive Officer: Catherine M. Rydell, CAE Managing Editor: Angela M. Babb, CAE, APR Editor: Tim Streeter Writers: Ryan Knoke, Sarah Parsons Designers: Siu Lee, Andrew Imholte Photography: Will Evans Printing: Phoenix Lithographing Corporation Email: aannews@aan.com AANextra is published by the American Academy of Neurology. 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.
Education Program syllabi and slides are available online only at AAN.com/view/syllabi or through the AAN Conferences Mobile App at AAN.com/view/MobileApp.
May 20 Is Deadline to Submit Online Evaluations for Annual Meeting CME Complete your evaluations to get your CME hours by using the AAN Conferences Mobile App at AAN.com/view/MobileApp or by visiting AAN.com/view/CME. CME requests may be made until Monday, May 20, 2019. Transcripts will be emailed approximately six weeks after the meeting. AAN members can also access their transcript via NeuroTracker™ at AAN.com/view/NeuroTracker.
SATUrDAY, MAY
4, 2019
ONAL RESEARCH LATEST TRANSLATI ’S HOT TOPICS PLENARY UNVEILED IN TODAY
THE ANNUAL
MEETING NEWS
DAILY
the Terrace Ballroom Make your way to hear 5:30 p.m. today to from 4:15 p.m. to speakers summarize four outstanding translational research their trailblazing of clinical implications and describe the session will be moderated the results. This Eric Committee Member by AAN Science of Massachusetts Klawiter, MD, FAAN, will use Boston, MA, and General Hospital, which allows attendees will Audience Response, that the moderator to submit questions To participate weave into the discussion. AAN.cnf.io or visit in Audience Response, Conferences App. connect via the AAN Continued on page
Klawiter
u 40
Vote on Board Axon Registry Experts Nominees at Today’s Meeting on Hand to Answer Philly Business the Your Questions in
to attend Members are encouraged Meeting being AAN’s 2019 Business p.m. in Room 204AB held today at 3:00 Convention Center, of the Philadelphia this election of the what the to participate in Have you ever wondered ® can do for your for AAN officer and slate of nominees term. AAN’s Axon Registry and get hands on for the 2019–2021 more director positions from practice? To learn for include reports this free AAN product The meeting will ts of the experience with your will help unlock officers on the accomplishmen US members that and a review of the by the Axon Registry AAN during 2018 practice data, stop atrium. health. the Broad Street organizations’ fiscal booth located in test opportunities to u 22 The booth will have talk with Continued on page dashboard, Registry the Axon get all your questions registry staff, and Registry, a qualityanswered. The Axon data qualified clinical improvement and solution to fulfilling registry, is your can requirements. It multiple regulatory meet your practice to also be used by Payment System Merit-based Incentive certain requirements and (MIPS) reporting Continued on page
Inside
6
2019 AAN Award Winners Announced
Inspiring and 30 Today’s to Innovative New Talk Explore Bionics
Philadelphia
for These 30 Look Opportunities for
‘Continuing the Conversation’ All Week Long
Calls for 31 AAN Uniformity of Brain
n Death Determinatio
u 37
The American Academy of Neurology sincerely thanks Phoenix Lithographing Corporation for its outstanding service, steadfast professionalism, and high quality standards, as well as its generous donation of the 2019 Brain Health Fair program guide.
ÑOL EN ESPA SO AL DOR
EVENT PROGRAM
Thursday, May 9, 2019 • 10:00 a.m.–4:00 p.m. Pennsylvania Convention Center
Welcome to the Annual Meeting! Have You Joined Us in Philly Before? Edgar J. Kenton III, MD, FAAN, was amused by the witty Benjamin Franklin. The late Kenton—a former board member and chair of the Practice Committee—will be honored posthumously this Wednesday with the American Brain Foundation Board Chair’s Award at the Commitment to Cures event.
The Mütter Museum at the College of Physicians of Philadelphia hosts a representative doctor’s office and an iron lung.
Don’t be surprised if you see Benjamin Franklin walking the streets of Philadelphia!
Former Presidents Roger S. Rosenberg, MD, FAAN; Sandra F. Olson, MD, FAAN; and Kenneth M. Viste, Jr., MD, FAAN, shared some time together.
Former Attorney General Janet Reno and AAN Chief Executive Officer Catherine M. Rydell, CAE. Rydell is now marking her 20th year as leader of the Academy’s staff.
Former President Lewis P. “Bud” Rowland, MD, FAAN, and his wife, Esther, met former Attorney General Janet Reno.
The AAN’s Annual Meeting has been held in the “City of Brotherly Love” four times: 1958, 1966, 2001, and 2014. While much has changed in the Annual Meeting over the years, the historic nature of Philadelphia celebrates the past as the city looks to the future. Former President Thomas R. Swift, MD, FAAN, led the applause for the 2014 Neurobowl winners.
Jellyroll is back for this year’s opening night party. Be sure to get your selfie
The 2014 Women in Leadership course offered a lively exchange of concerns and viewpoints.
Connecting with colleagues and networking is a mainstay of any Annual Meeting.
This group of attendees traveled from Egypt to partake of the latest in neurology science and education.
Attendees found a wealth of knowledge at the many education courses.
The 2014 Women in Leadership course had strong attendance.
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2019 AAN Award Winners Announced Congratulations to the winners of the 2019 AAN awards. Most of these recipients will be celebrated with presentations of their awards during the Annual Meeting in Philadelphia, and some will present papers at the following noted times. The AAN thanks the American Brain Foundation for its support through philanthropy of the American Academy of Neurology's awards program. A.B. BAKER AWARD FOR LIFETIME ACHIEVEMENT IN NEUROLOGIC EDUCATION Funded by an endowment created by matching funds from the A.B. Baker Family Trust and Novartis Pharmaceuticals. Steven L. Lewis, MD, FAAN / Allentown, PA A.B. BAKER TEACHER RECOGNITION AWARD Jorge J. Asconape, MD / Maywood, IL / Loyola University Chicago James Nicholas Brenton, MD / Charlottesville, VA / University of Virginia Kevin R. Cannard, MD, FAAN / Bethesda, MD / Walter Reed NMMC Miguel Chuquilin Arista, MD / Gainesville, FL / University of Florida Glen A. Cook, Jr., MD / Bethesda, MD / Walter Reed National Military Medical Center Monica B. Dhakar, MBBS / Atlanta, GA / Emory University School of Medicine Vanja C. Douglas, MD / San Francisco, CA / University of California, San Francisco Steven Richard Dunham, Jr., MD / Houston, TX / Baylor College of Medicine Jeffrey E. Dunn, MD, FAAN / Palo Alto, CA / Stanford University Medical Center Benjamin H. Eidelman, MB, FAAN / Jacksonville, FL / Mayo Clinic, Florida Gary Gallagher, MD / Ann Arbor, MI / University of Michigan Tarannum Khan, MD, MBBS / Weston, FL / Cleveland Clinic, Florida Arielle Marisa Kurzweil, MD / New York, NY / New York University Shaheen E. Lakhan, MD, PhD, MEd, FAAN / Somerville, MA / Virginia Tech Kaustubh S. Limaye, MD / Iowa City, IA / University of Iowa
Georgios Manousakis, MD / Minneapolis, MN / University of Minnesota Matthew A. McCoyd, MD / Maywood, IL / Loyola University, Stritch School of Medicine Prachi Mehndiratta, MD / Henrico, VA / Virginia Commonwealth University Nicte I. Mejia, MD, MPH, FAAN / Boston, MA / Massachusetts General Hospital Jeremy Moeller, MD / New Haven, CT / Yale University Jonathan Perk, MD, PhD / Brooklyn, NY / SUNY Downstate University Alejandro A. Rabinstein, MD, FAAN / Rochester, MN / Mayo Clinic Mehmood Rashid, MD / Toledo, OH / University of Toledo, College of Medicine & Life Sciences Yolanda Reyes-Iglesias, MD / Miami, FL / University of Miami, Miller School of Medicine Debra Roberts, MD, PhD / Rochester, NY / University of Rochester Medical Center Julie Roth, MD, FAAN / Providence, RI / Brown University Divya Singhal, MD / Oklahoma City, OK / University of Oklahoma/VAMC Oklahoma City Madhu Soni, MD, FAAN / Chicago, IL / Rush University Medical Center Roy E. Strowd III, MD / Winston Salem, NC / Wake Forest School of Medicine Lisa Sun, MD / Baltimore, MD / Johns Hopkins School of Medicine David F. Tang-Wai, MD, FRCPC / Toronto, ON / Toronto Western Hospital/University Health Network Joanne M. Wojcieszek, MD / Indianapolis, IN / IU Health Neuroscience Center ADVANCED PRACTICE PROVIDER SCHOLARSHIP Sponsored by the AAN Practice Committee. Mary Epperson, RN, BSN, MSN, CPNP / St. Louis, MO Christa S. Cooper, PA-C, MMS, MPH / Chicago, IL ALLIANCE AWARDS Sponsored by the American Academy of Neurology and endowed by the former American Academy of Neurology Alliance.
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Saturday, May 4, 2019 • AANextra
FOUNDERS AWARD Lily Zhou, MD / Ottawa, ON, Canada S40: Stroke Risk Factors and Epidemiology Wednesday, May 8, 3:30 p.m. S. WEIR MITCHELL AWARD Andrew Findlay, MD / St. Louis, MO S23: Genetic Muscle Disorders Monday, May 6, 3:30 p.m. AMERICAN ACADEMY OF NEUROLOGY PRESIDENT’S AWARD This award is given by the American Academy of Neurology president for outstanding service to the American Academy of Neurology and the profession of neurology. Lisa M. DeAngelis, MD, FAAN / New York, NY AMERICAN BRAIN FOUNDATION BOARD CHAIR’S AWARD Sponsored by the American Brain Foundation. Edgar J. Kenton III, MD, FAAN, FAHA (given posthumously) / Philadelphia, PA Commitment to Cures Wednesday, May 8, 6:00 p.m. ASSOCIATION OF INDIAN NEUROLOGISTS IN AMERICA LIFETIME ACHIEVEMENT AWARD Sponsored by the American Brain Foundation. Ram Ayyar, MD, FAAN / Miami, FL AINA Annual Meeting / Monday, May 6, 6:00 p.m. AWARD FOR CREATIVE EXPRESSION OF HUMAN VALUES IN NEUROLOGY This award is sponsored by the Ethics, Law, and Humanities Committee, a joint committee of the American Academy of Neurology, the American Neurological Association, and the Child Neurology Society. Ludwig Gutmann, MD, FAAN / Iowa City, IA The Intolerable Burden BRUCE S. SCHOENBERG INTERNATIONAL AWARD IN NEUROEPIDEMIOLOGY Sponsored by the American Academy of Neurology and endowed by GlaxoSmithKline, Inc. This award was not given for 2019. CHILD NEUROLOGY NEUROSCIENCE RESEARCH PRIZE Sponsored by the American Academy of Neurology and the Child Neurology Society. Shan Lateef / Alexandria, VA Child Neurology Society Meeting October 23–26, 2019 / Charlotte, NC
CLERKSHIP COORDINATOR RECOGNITION AWARD Sponsored by the American Academy of Neurology. Christina Cronin / Coram, New York / NYU Langone Health CLERKSHIP COORDINATOR RECOGNITION AWARD Sponsored by the American Academy of Neurology. Celia Linton / Casselberry, Florida / University of Central Florida CLERKSHIP DIRECTOR INNOVATION AWARD Sponsored by the American Academy of Neurology. Doris Kung, DO / Houston, Texas / Baylor College of Medicine CLERKSHIP DIRECTOR TEACHING AWARD Sponsored by the American Academy of Neurology Diana Barratt, MD, MPH, FAAN / Miami, Florida / Florida International University COMMITMENT TO CURES AWARD Sponsored by the American Brain Foundation. Jeffrey Lurie / Philadelphia, PA Commitment to Cures Wednesday, May 8, 6:00 p.m. CONSORTIUM OF NEUROLOGY RESIDENTS AND FELLOWS ESSAY CONTEST Bryan J. Neth, MD, PhD / Rochester, MN / Mayo Clinic DREIFUSS-PENRY EPILEPSY AWARD Sponsored by the American Academy of Neurology and endowed by members of the American Academy of Neurology Epilepsy Section; Abbott Laboratories, Inc.; Cephalon, Inc.; Cyberonics, Inc.; Elan Pharmaceuticals, Inc.; GlaxoSmithKline; Novartis Neuroscience; Ortho-McNeil Neurologics; Pfizer Inc; Shire US, Inc; and UCB Pharma. Daniel Friedman, MD / New York, NY S36: Epilepsy/Clinical Neurophysiology (EEG) II Wednesday, May 8, 1:00 p.m. ENHANCED RESIDENT LEADERSHIP PROGRAM Supported in part by Greenwich Biosciences, Inc. Rachel Forman, MD / Chicago, IL / Rush University Medical Center
Liana Theroux, MD / Charlottesville, VA / University of Virginia School of Medicine Maureen Handoko, MD, PhD / Houston, TX / Baylor College of Medicine Ezequiel Gleichgerrcht, MD / Charleston, SC / Medical University of South Carolina Neda Zarghami Esfahani, MD / Iowa City, IA / University of Iowa Hospitals and Clinics Vijay Ramanan, MD, PhD / Rochester, MN / Mayo Clinic Long Davalos, MD / Cincinnati, OH / University of Cincinnati College of Medicine Margaret Blattner, MD, PhD / Saint Louis, MO / Washington University in St. Louis Elizabeth Duke, MD / Boston, MA / Boston Children's Hospital Sarah Woodson, MD / Bethesda, MD / NCC Walter Reed National Military Medical Center Saima Chaudhry, MD / Maywood, IL / Loyola University Medical Center Darrah Haffner, MD, MHS / Dallas, TX / University of Texas Southwestern Medical School Ashby Turner, MD / Cincinnati, OH / University of Cincinnati College of Medicine Allison Crowell, MD / Charlottesville, VA / University of Virginia Alicia Henriquez, MD / Aurora, CO / University of Colorado School of Medicine FRANK A. RUBINO AWARD FOR EXCELLENCE IN CLINICAL NEUROLOGY TRAINING Funded by Mayo Clinic Frank A. Rubino, MD, Development Fund. Allen J. Aksamit, Jr. MD, FAAN / Rochester, MN / Mayo Clinic H. RICHARD TYLER AWARD Sponsored by the American Academy of Neurology and the American Academy of Neurology History Section. This award was not given in 2019. HAROLD WOLFF-JOHN GRAHAM AWARD: AN AWARD FOR HEADACHE/FACIAL PAIN RESEARCH Sponsored by the American Academy of Neurology and endowed by Endo Pharmaceuticals.
Jelena Pavlovic, MD, PhD / New York, NY S20: Headache Imaging and Physiology and Episodic Syndromes Associated with Migraine Monday, May 6, 3:30 p.m. INTERNATIONAL SCHOLARSHIP AWARD Sponsored by the American Academy of Neurology. Dona-Hui Ao, MD / Beijing, China Babawale Arabambi, MBBS, FWACP / Lagos, Nigeria Marjorie Anne Bagnas, MD / Manila, Philippines Abiodun Bello, MBBS, FWACP / Ilorin, Nigeria Ismael Calandri, MD / Buenos Aires, Argentina Fabricio Castro de Borba, MD / São Paulo, Brazil Filipe Brogueira Rodrigues, MD, MSc / London, United Kingdom Ismael Calandri, MD / Buenos Aires, Argentina Avinash Chandra, MD / Kathmandu, India Marienke de Bruijn, MD / Tilburg, Netherlands Guillermo Delgado-Garcia, MD / Mexico City, Mexico Lingling Ding, MD / Beijing, China Victoria Carla Fernandez, MD / Buenos Aires, Argentina Divyani Garg, MBBS, MD / New Delhi, India Alicia Gonzalez-Martinez, MD / Madrid, Spain Wijoyo Halim, MD / Palu, Indonesia Joyce Jimenez-Zambrano, MD / Guayaquil, Ecuador Marilise Katsurayama, MD / São Paulo, Brazil Ravish Keni, MBBS, MD / Thiruvananthapuramm, India Priyanka Madaan, MD, DM / Chandigarh, India Mark Willy Mondia, MD / Manila, Philippines Tshering Pem, MBBS / Thimphu, Bhutan Chintan Prajapati, MBBS, MD / New Delhi, India Ahmed Effat Saied, MD, MSc / Mansoura, Egypt Lucas Scárdua Silva, MD / Campinas, Brazil Salma Suhana, MBBS, MD / Davanagere, India Satish Wagh, MD / Puducherry, India Sonam Yangzom, MBBS / Thimphu, Bhutan Florencia Yorio, MD / Buenos Aires, Argentina Stanley Zimba, MBChB, MMed / Lusaka, Zambia IRWIN SCHATZ AWARD FOR AUTONOMIC DISORDERS Sponsored by the American Academy of Neurology and endowed by Lundbeck, Inc. Roy Freeman, MD / Boston, MA S18: Autonomic Disorders Monday, May 6, 3:30 p.m. Continued on page 11
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With hereditary transthyretin-mediated (hATTR) amyloidosis...
Patients and their families face a future of functional decline1-3
Important Safety Information Infusion-Related Reactions (IRRs) In a controlled clinical study, 19% of ONPATTROtreated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache. To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and Recommended Supplementation ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness). Adverse Reactions The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%). Please see brief summary of full Prescribing Information following this ad.
References: 1. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013; 8:31. 2. Coutinho P, Martins da Silva A, Lopes Lima JL, et al. Excerpta Medica; 1980:88-98. 3. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119. 4. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018. 5. Adams D, Coelho T, Obici L, et al. Neurology. 2015;85(8):675-682. 6. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21. 7. Center for Drug Evaluation and Research. NDA 210922—patisiran—cross-discipline team leader review. U.S. Department of Health and Human Services, Food and Drug Administration; 2018. ONPATTRO is a registered trademark of Alnylam Pharmaceuticals, Inc. © 2019 Alnylam Pharmaceuticals, Inc. All rights reserved. TTR02-USA-00023-012019
ONPATTRO® (patisiran) can reverse polyneuropathy manifestations of the disease4 A novel RNAi-based approach that may transform the future for your patients1,4-6 ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
At 18 months, ONPATTRO demonstrated: Reversal in neuropathy impairment4
Study Design The efficacy of ONPATTRO was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adults with hATTR amyloidosis with polyneuropathy. Patients were randomized to receive ONPATTRO 0.3 mg/kg (N=148) or placebo (N=77) via intravenous infusion once every 3 weeks for 18 months. Primary endpoint: The modified Neuropathy Impairment Score + 7 (mNIS+7) is an objective 304-point assessment of neuropathy that measures cranial nerve function, muscle strength, reflexes, postural blood pressure, quantitative sensory testing, and peripheral nerve electrophysiology. Key secondary endpoint: The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) scale is a patient-reported assessment that evaluates neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy (score range -4 to 136). Select secondary endpoint: The Composite Autonomic Symptom Score 31 (COMPASS 31) is a patient-reported questionnaire that evaluates 6 autonomic domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor (score range 0 to 100).
• Mean change from baseline in mNIS+7 of -6.0 points vs 28.0 with placebo, a treatment difference of -34 points (95% CI: -39.9, -28.1; p<0.001)
Improvement in quality of life4 • Mean change from baseline in Norfolk QoL-DN score of -6.7 points vs 14.4 with placebo, a treatment difference of -21.1 points (95% CI: -27.2, -15.0; p<0.001)
Reduction in autonomic symptoms6,7 • Mean change from baseline in COMPASS 31 of -5.3 points vs 2.2 with placebo, a treatment difference of -7.5 points (95% CI: -11.9, -3.2; p<0.001) CI=confidence interval; RNA=ribonucleic acid; RNAi=RNA interference.
Visit Booth #2401 to find out more.
2019 AAN Award Winners Announced continued from page 7 JOHN DYSTEL PRIZE FOR MULTIPLE SCLEROSIS RESEARCH Sponsored by the American Academy of Neurology and National Multiple Sclerosis Society and made possible through a special contribution from the John Dystel Multiple Sclerosis Research Fund at the National Multiple Sclerosis Society. Anne Cross, MD, FAAN / St. Louis, MO The Grand Experience—Grand Hall, Stage 1 Wednesday, May 8, 3:30 p.m. JON STOLK AWARD IN MOVEMENT DISORDERS FOR YOUNG INVESTIGATORS Sponsored by the American Academy of Neurology and endowed by Kyowa Pharmaceutical, Inc., Lineberry Research, Quintiles, Dr. Dennis Gillings, and VelaPharma. Sheng-Han Kuo, MD / New York, NY S41: Imaging in Movement Disorders Wednesday, May 8, 3:30 p.m. KENNETH M. VISTE, JR., MD, PATIENT ADVOCATE OF THE YEAR AWARD Sponsored by the American Academy of Neurology and endowed by gifts from Dr. Viste’s colleagues, friends, and patients. Aaron L. Berkowitz, MD, PhD / Boston, MA LAWRENCE C. MCHENRY AWARD: AN AWARD FOR THE HISTORY OF NEUROLOGY Sponsored by the American Academy of Neurology. Stefano Sandrone, PhD / Milan, Italy S44: History of Neurology Thursday, May 9, 1:00 p.m. MEDICAL STUDENT DIVERSITY SCHOLARSHIPS Supported in part by grants from The Allergan Foundation. Laura Hernandez-Miyares / Philadelphia, PA / University of Pennsylvania, Perelman School of Medicine Kelly Boylan / Philadelphia, PA / University of Pennsylvania, Perelman School of Medicine Ganaelle Joseph-Senatus / Valhalla, New York / New York Medical College William Barbosa / New York, New York / New York University School of Medicine Felicia Cooper / Hershey, PA / Pennsylvania State University College of Medicine Joseph Aderemi / Auburn Hills, MI / Oakland University William Beaumont (OUWB) School of Medicine Danielle Kellier / Philadelphia, PA / University of Pennsylvania, Perelman School of Medicine Jonathan Rodriguez / Caguas, Puerto Rico / San Juan Bautista School of Medicine Dayne Martinez / Philadelphia, PA / University of Pennsylvania, Perelman School of Medicine Mahdieh Hosseini / Philadelphia, PA / Lewis Katz School of Medicine at Temple University
MEDICAL STUDENT ESSAY AWARDS Sponsored by the American Academy of Neurology. Extended Neuroscience Award Laura McGarry, PhD / New York, NY Poster Session 2 / Monday, May 6, 11:30 a.m. G. Milton Shy Award in Clinical Neurology Audrey Leasure / New Haven, CT Poster Session 2 / Monday, May 6, 11:30 a.m. Roland P. Mackay Award in Historical Aspects Stephanie Roses / Durham, NC Poster Session 2 / Monday, May 6, 11:30 a.m. Saul R. Korey Award in Experimental Neurology Sona Mistry / Sheffield, United Kingdom Poster Session 2 / Monday, May 6, 11:30 a.m. MICHAEL S. PESSIN STROKE LEADERSHIP PRIZE Sponsored by the American Academy of Neurology and endowed by Dr. Pessin’s family, friends, and colleagues.
Guenther Deuschl, MD, PhD, FAAN / Kiel, Germany S16: Huntington’s Disease: From Bench to Clinical Trials Monday, May 6, 1:00 p.m. MRIDHA SPIRIT OF NEUROLOGY HUMANITARIAN AWARD Sponsored by the American Brain Foundation and funded through the philanthropy of Dr. and Mrs. Mridha. James H. Bower, MD, MSc, FAAN / Rochester, MN Global Health Section Meeting Monday, May 6, 8:15 a.m. NEUROENDOCRINE RESEARCH AWARD Sponsored by the American Academy of Neurology and supported by friends of Dr. Andrew Herzog. Dena Dubal, MD, PhD / San Francisco, CA Neuroendocrinology Section Meeting NEUROLOGY® RESIDENT & FELLOW SECTION WRITING AWARD Nathaniel M. Schuster / University of California, San Diego, MD Jacob R. Hascalovici, MD, PhD / Albert Einstein College of Medicine
Alessandro Biffi, MD / Boston, MA S22: Stroke Genetics, Cellular Responses, and Animal Models Monday, May 6, 3:30 p.m. MITCHELL B. MAX AWARD FOR NEUROPATHIC PAIN Sponsored by the American Academy of Neurology and endowed by the United States Cancer Pain Relief Committee, the Mayday Fund, and friends of Dr. Mitchell Max. Troels Staehelin Jensen, MD, PhD / Aarhus, Denmark S24: L ost Connections: From Functional Connectivity to Needs in Pain and Palliative Care Tuesday, May 7, 1:00 p.m.
NEURO-ONCOLOGY INVESTIGATOR AWARD Sponsored by the American Academy of Neurology and supported by friends of Dr. Jerome Posner. Jorg Dietrich, MD, PhD, FAAN / Boston, MA S14: Translational and Clinical Advances in Neuro-oncology Monday, May 6, 1:00 p.m. NEURO-ONCOLOGY SCIENTIFIC AWARD Sponsored by the American Academy of Neurology and supported by friends of Dr. W.K. Alfred Yung.
MOVEMENT DISORDERS RESEARCH AWARD Sponsored by the American Academy of Neurology, the Parkinson’s Foundation, and the American Academy of Neurology Movement Disorders Section and endowed by the Parkinson’s Foundation.
Andreas von Deimling, MD / Heidelberg, Germany S14: Translational and Clinical Advances in Neuro-oncology Monday, May 6, 1:11 p.m. Continued on page 12
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2019 AAN Award Winners Announced continued from page 11 NEUROSCIENCE RESEARCH PRIZE Funded by the American Academy of Neurology. Rachel Chernoff / Armonk, NY Poster Session 1 / Sunday, May 5, 11:30 a.m. Kevin Zhong / Basking Ridge, NJ Poster Session 1 / Sunday, May 5, 11:30 a.m. Caleb Shi / Hackensack, NJ Poster Session 1 / Sunday, May 5, 11:30 a.m. NORMAN GESCHWIND PRIZE IN BEHAVIORAL NEUROLOGY Sponsored by the American Academy of Neurology and endowed through Dr. Geschwind’s family, friends, and colleagues; Pfizer Inc; and the Society for Behavioral and Cognitive Neurology. Sonja Scholz, MD / Bethesda, MD S13: Behavioral and Cognitive Neurology: Behavioral Neurology, Aging, and Dementia Monday, May 6, 1:00 p.m. POTAMKIN PRIZE FOR RESEARCH IN PICK’S, ALZHEIMER’S, AND RELATED DISEASES Sponsored by the American Academy of Neurology and the American Brain Foundation and funded through the philanthropy of the Potamkin family. Randall Bateman, MD / St. Louis, MO The Grand Experience—Grand Hall, Stage 1 / Monday, May 6, 3:30 p.m. PROGRAM COORDINATOR RECOGNITION AWARD Ann Chowdhury Johnson, BA, C-TAGME / Phoenix, AZ / Barrow Neurological Institute Michelle R. Armstrong, MAEd, C-TAGME / Maywood, IL / Loyola University Medical Center PROGRAM DIRECTOR RECOGNITION AWARD Audrey Foster-Barber, MD, PhD / San Francisco, CA / UCSF Child Neurology Donald Gilbert, MD, FAAN / Cincinnati, OH / Cincinnati Children's Hospital Medical Center PUBLIC LEADERSHIP IN NEUROLOGY AWARD Sponsored by the American Brain Foundation. Ann Romney / Salt Lake City, UT Commitment to Cures Wednesday, May 8, 6:00 p.m. SAFETY AND QUALITY AWARD Sponsored by the American Academy of Neurology. Monisha A. Kumar, MD, and David G. Coughlin, MD / Philadelphia, PA Green Sheet Tool to Limit Unplanned ICU Readmission Danielle Larson, MD / Chicago, IL Development of a Parkinson’s Disease-specific Admission Order Set and Its Impact on Inpatient Medication Administration
Elanagan Nagarajan, MD / Columbia, MO Hematoma Risk After Needle EMG in Patients with Newer Anticoagulation Minh-Thuy Nguyen / Boston, MA Improving Stroke Education in Spanish-speaking Patients SHEILA ESSEY AWARD: AN AWARD FOR ALS RESEARCH Sponsored by the American Academy of Neurology, the American Brain Foundation and the ALS Association and supported through the philanthropy of the Essey Family and the ALS Association. Aaron Gitler, PhD / Stanford, CA The Grand Experience—Grand Hall, Stage 1 / Tuesday, May 7, 3:30 p.m. SLEEP SCIENCE AWARD Sponsored by the American Academy of Neurology and the American Academy of Neurology Sleep Section and endowed by Cephalon, Inc. Clifford Saper, MD, PhD, FAAN / Boston, MA S46: Sleep Science and Therapy Updates Thursday, May 9, 1:00 p.m. WAYNE A. HENING SLEEP MEDICINE INVESTIGATOR AWARD Sponsored by the American Academy of Neurology and endowed by UCB, Inc., Lilly USA, Elite Home Medical & Respiratory, Inc., Raleigh Neurology Associates, and friends of Dr. Wayne A. Hening. Diego Carvalho, MD / Rochester, MN S46: Sleep Science and Therapy Updates Thursday, May 9, 1:22 p.m.
2019 RESEARCH PROGRAM RECIPIENTS
CAREER DEVELOPMENT AWARD Funded by the American Academy of Neurology. Shouri Lahiri, MD / Cedars-Sinai Medical Center Susanna Mierau, MD, PhD / University of Cambridge
CLINICAL RESEARCH TRAINING SCHOLARSHIP Funded by the American Academy of Neurology. Prashanth Ramachandran, MBBS / University of California, San Francisco Karisa Schreck, MD, PhD / Johns Hopkins University Jennifer Kim, MD, PhD / Massachusetts General Hospital, Brigham and Women’s, Harvard CLINICAL RESEARCH TRAINING SCHOLARSHIP IN ALS Funded by The ALS Association and American Brain Foundation in collaboration with the American Academy of Neurology. Jennifer Marsella, MD / University of Rochester CLINICAL RESEARCH TRAINING SCHOLARSHIP IN HEADACHE Funded by the International Headache Society and American Brain Foundation in collaboration with the American Academy of Neurology. Faisal Amin, MD, PhD / Rigshospitalet CLINICAL RESEARCH TRAINING SCHOLARSHIP IN MULTIPLE SCLEROSIS Funded by the Consortium of Multiple Sclerosis Centers, Biogen, in collaboration with the American Brain Foundation. Ulrike Kaunzner, MD / New York Presbyterian Hospital, Weill Cornell Medical Center CLINICAL RESEARCH TRAINING SCHOLARSHIP IN MUSCULAR DYSTROPHY Funded by the Muscular Dystrophy Association and American Brain Foundation in collaboration with the American Academy of Neurology. This award was not given for 2019. CLINICAL RESEARCH TRAINING SCHOLARSHIP IN NEUROMUSCULAR DISEASE Funded by the Muscle Study Group and American Brain Foundation in collaboration with the American Academy of Neurology. Continued on page 14
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What’s the key to breakthrough Neuro research and treatments? Collaboration. At NewYork-Presbyterian Hospital, we partner with specialists
from Columbia University Vagelos College of Physicians and Surgeons and Weill Cornell Medicine to provide care to thousands of neurology and neurosurgery patients. Faculty from both medical schools are at the forefront of conducting research and clinical studies for a wide range of conditions. Recent advances include: Alzheimer’s • A study that uncovered large-scale changes throughout the epigenome of the human Alzheimer’s disease brain, revealing that tau-induced alterations of chromatin structure are more profound than changes attributable to amyloid pathology. • The launch of our new Alzheimer’s Prevention Clinic that combines evidence-based, low-risk interventions with lifestyle modifications that may help to delay, or in some cases possibly prevent, the progression towards dementia. Brain Tumors • The first-ever dose escalation study using convection-enhanced delivery for diffuse intrinsic pontine glioma to bypass the blood-brain barrier and administer a drug directly to the brain stem tumor site. Stroke • Participated in the DEFUSE trial which has shown the benefit of late thrombectomy from 6 to 24 hours past onset of a large vessel occlusive stroke. Because of these innovations and more, our Neurology and Neurosurgery program is ranked #1 in New York and #5 in the nation by U.S. News & World Report.
Learn more at nyp.org/neuroinnovations
New York’s #1 hospital for a reason. Source: New York’s #1 hospital as ranked by U.S. News & World Report 2018-19
2019 AAN Award Winners Announced continued from page 12 Reza Sadjadi, MD / Massachusetts General Hospital, Brigham and Women’s, Harvard Medical School CLINICAL RESEARCH TRAINING SCHOLARSHIP IN PARKINSON’S DISEASE Funded by the Parkinson’s Foundation and American Brain Foundation in collaboration with the American Academy of Neurology. David Coughlin, MD / University of Pennsylvania CLINICAL RESEARCH TRAINING SCHOLARSHIP IN PARKINSON’S DISEASE Funded by the Parkinson’s Foundation and American Brain Foundation in collaboration with the American Academy of Neurology, supported in part by a grant from AbbVie. Anna Goodheart, MD / Massachusetts General Hospital, Brigham and Women’s, Harvard Medical School CLINICAL RESEARCH TRAINING SCHOLARSHIP IN TOURETTE SYNDROME Funded by the Tourette Association of America and American Brain Foundation in collaboration with the American Academy of Neurology. Jennifer Vermilion, MD / University of Rochester CLINICIAN SCIENTIST DEVELOPMENT AWARD IN INTERVENTIONAL NEUROLOGY Funded by the Society of Vascular and Interventional Neurology and American Brain Foundation in collaboration with the American Academy of Neurology. Kevin Keenan, MD / University of California, Davis in Davis, CA CLINICIAN SCIENTIST DEVELOPMENT AWARD IN MULTIPLE SCLEROSIS Funded by the National Multiple Sclerosis Society and American Brain Foundation. Omar Al-Louzi, MD / National Institutes of Health CLINICIAN SCIENTIST DEVELOPMENT AWARD IN MYASTHENIA GRAVIS Funded by the Myasthenia Gravis Foundation of America and American Brain Foundation in collaboration with the American Academy of Neurology. Shruti Raja, MD / Duke University Medical Center LAWRENCE M. BRASS STROKE RESEARCH AWARD Funded by the American Heart Association and American Stroke Association and the American Brain Foundation. Juneyoung Lee, PhD / Houston, TX / University of Texas Health
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MCKNIGHT CLINICAL TRANSLATIONAL RESEARCH SCHOLARSHIP IN COGNITIVE AGING AND AGE-RELATED MEMORY LOSS Funded by the McKnight Brain Research Foundation through the American Brain Foundation, and the American Academy of Neurology. Sanaz Sedaghat, PhD / Feinberg School of Medicine, Northwestern University Christian Camargo, MD / University of Miami School of Medicine NEUROSCIENCE RESEARCH TRAINING SCHOLARSHIP Funded by the American Academy of Neurology. Isabel Lam, PhD / Boston, MA / Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School Victoria Ho, MD, PhD / UCLA Kellen Winden, MD, PhD / Children’s Hospital Boston
Join Us in Celebrating Awards in a New Way! Join us at The Grand Experience— Grand Hall, Stage 1 for three special award presentations, each followed by a panel Q&A discussion with past award recipients.
PRACTICE RESEARCH TRAINING SCHOLARSHIP Funded by the American Academy of Neurology.
Monday, May 6 at 3:30 p.m. Recipient: Randall Bateman, MD Panelists: David M. Holtzman, MD, FAAN; Virginia Lee, PhD; and Reisa A. Sperling, MD
Elan Guterman, MD / University of California, San Francisco RICHARD OLNEY CLINICIAN SCIENTIST DEVELOPMENT AWARD IN ALS Funded by The ALS Association and American Brain Foundation in collaboration with the American Academy of Neurology.
Suma Babu, MBBS / Massachusetts General Hospital, Brigham and Women’s, Harvard Medical School ROBERT W. KATZMAN, MD, CLINICAL RESEARCH TRAINING SCHOLARSHIP IN ALZHEIMER’S AND DEMENTIA RESEARCH Funded by the Alzheimer’s Association and American Brain Foundation in collaboration with the American Academy of Neurology. William G. Mantyh, MD / University of California, San Francisco SUSAN SPENCER, MD CLINICAL RESEARCH TRAINING SCHOLARSHIP IN EPILEPSY Funded by the American Epilepsy Society, Epilepsy Foundation, and American Brain Foundation in collaboration with the American Academy of Neurology. Lisseth Burbano, MD / Florey Institute of Neuroscience and Mental Health
Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Diseases
Sheila Essey Award: An Award for ALS Research Tuesday, May 7 at 3:30 p.m. Recipient: Aaron Gitler, PhD Panelists: Merit Cudkowicz, MD, MSc; Serge Przedborski, MD, PhD; and Jeremy Shefner, MD, PhD, FAAN
John Dystel Prize for Multiple Sclerosis Research Wednesday, May 8 at 3:30 p.m. Recipient: Anne Cross, MD Panelists: Cedric S. Raine, PhD, DSc; Lawrence Steinman, MD, FAAN; Jack P. Antel, MD, FAAN; and Howard L. Weiner, MD
Come visit us at Booth 1341 or online at www.spinraza-hcp.com/congress to learn more
Š2019 Biogen. All rights reserved. SPZ-US-2226 03/19
Today’s Experiential Learning Area Highlights HeadTalks
Maximize Your Value and Advocacy to Action Opioids: What Is Your State Doing to Confront this Epidemic? 4:00 p.m.–4:45 p.m.
Bickel
Choe
Pazdan
Santini
Women in Neurology 3:45 p.m.–4:45 p.m. Successful women in neurology will share their leadership journeys and discuss their challenges and successes throughout their careers: Jennifer Bickel, MD, FAAN; Meeryo Choe, MD; Renee M. Pazdan, MD, FAAN; and Veronica E. Santini, MD.
Live Well: Taking Care of Your Patients Starts with Taking Care of You Laughter Yoga 8:00 a.m.–8:45 a.m. Participants will learn about the Laughter Yoga global movement for well-being. A typical session includes laughter, movement, singing, dancing, breathing exercises, playfulness, and stillness. It will be an uplifting, energizing, and joyful experience.
Dancing with Parkinson’s 2:30 p.m.–3:15 p.m. A brief summary of why dance helps and what it improves for people with Parkinson's disease, followed by a video and live demonstration with audience participation.
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Saturday, May 4, 2019 • AANextra
Donn Dexter, MD, FAAN, discusses how opioid overuse has prompted individual states to address this crisis. What does this mean for you and your practice?
Dexter
Research Corner How to Successfully Publish Quality Improvement Projects 9:00 a.m.–9:30 a.m. Anup Patel, MD, FAAN, will share information about how to structure your QI project for publication, the SQUIRE 2.0 guidelines for publishing QI, and also which journals in neurology are good places to submit the QI manuscript.
Patel
Navigating Your Career A Career in Neuroimaging 2:00 p.m.–2:45 p.m. Michael Hutchinson, MD, PhD, states: “Neuroimaging is central to all neurological subspecialties, yet most readers are general Hutchinson radiologists. Yet, neuroimaging fellowships are growing and UCNS certification is accepted by most insurance companies. We estimate that 800 neurologists, mostly in the southeast US, provide official reports on their patients. Soon, an MRI scan will take seconds and will be capable of imaging thoracic and abdominal organs. Neurologists must get more involved or be left behind.”
Experience the AAN Find out how the AAN supports and works for you. Congratulate your deserving colleagues featured on the recognition walls!
Mobile App Makes Planning Your Week in Philly Easy Looking for an easy way to plan your schedule this week? Look no further than the AAN Conference App! Visit AAN.com/view/MobileApp to download it to your iPhone, iPad, or Android, then:
iew the most up-to-date information on speakers and V talk topics uild your personalized program schedule, including B taking advantage of our specially curated program tracks Discover Annual Meeting highlights and can’t-miss events
Locate your favorite programs and vendors ap into information about Philadelphia, including T the hotel map and local attractions ead what’s being said at the Annual Meeting and R join the conversation using #AANAM on Facebook, Twitter, and Instagram Live stream select courses and sessions ccess program materials, submit your program A evaluations, and claim CME post-Annual Meeting
Be sure to check out these new features! Live stream select programs and courses from anywhere in
the Pennsylvania Convention Center
Use improved filters to search for courses by topics or
by tracks, including the new Academic Medicine, Career Essentials, and Futures in Neurological Research Tracks
The AAN Conferences App is sponsored by EMD Serono, Inc.
Saturday, May 4, 2019 • AANextra
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APPROVED FOR USE IN PEDIATRIC PATIENTS WITH EPILEPSY
4 YEARS OF AGE AND OLDER WITH PARTIAL-ONSET SEIZURES
FYCOMPA® (perampanel) is indicated in patients with epilepsy aged 4 years and older for partial-onset seizures (POS) with or without secondarily generalized seizures and adjunctive therapy for patients aged 12 years and older for primary generalized tonic-clonic (PGTC) seizures.
RETHINK YOUR APPROACH
TO CONVULSIVE SEIZURE FREEDOM
FIND OUT MORE AT BOOTH 2017 OR VISIT FYCOMPA.COM/HCP
Please see Important Safety Information, including a Boxed WARNING for Serious Psychiatric and Behavioral Reactions, on adjacent page. Please see Brief Summary of Prescribing Information on following pages.
IMPORTANT SAFETY INFORMATION WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS • Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA® • These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression • Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA • Closely monitor patients particularly during the titration period and at higher doses • FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening
SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.
SUICIDAL BEHAVIOR AND IDEATION Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
DIZZINESS AND GAIT DISTURBANCE FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35% and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.
SOMNOLENCE AND FATIGUE FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo-treated patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known.
FALLS Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement. If signs or symptoms are present, immediately evaluate the patient and discontinue FYCOMPA if an alternative etiology for signs or symptoms cannot be established.
WITHDRAWAL OF AEDs A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.
MOST COMMON ADVERSE REACTIONS The most common adverse reactions in patients aged 12 years and older receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety. Adverse reactions in patients aged 4 to <12 years were generally similar to patients aged 12 years and older.
DRUG INTERACTIONS FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of perampanel were decreased when administered with known moderate and strong CYP3A4 inducers, including, carbamazepine, phenytoin, or oxcarbazepine. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.
PREGNANCY AND LACTATION Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.
HEPATIC AND RENAL IMPAIRMENT Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.
DRUG ABUSE AND DEPENDENCE FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence and withdrawal symptoms including anxiety, nervousness, irritability, fatigue, asthenia, mood swings, and insomnia.
Please see Brief Summary of Prescribing Information on following pages. FYCOMPA® is a registered trademark of Eisai R&D Management Co., Ltd., licensed to Eisai Inc. ©2019 Eisai Inc. FYCO-US2654 February 2019
FYCOMPA® (perampanel) tablets, for oral use, CIII FYCOMPA® (perampanel) oral suspension, CIII Initial U.S. Approval: 2012 Brief Summary of Full Prescribing Information dated September 2018 WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS • Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA. • These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. • Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA. • Closely monitor patients particularly during the titration period and at higher doses • FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening. WARNINGS AND PRECAUTIONS Serious Psychiatric and Behavioral Reactions In the controlled partial-onset seizure clinical trials, hostilityand aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. FYCOMPA-treated patients experienced more hostility- and aggression-related adverse reactions that were serious, severe, and led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. In general, in placebo-controlled partial-onset seizure clinical trials, neuropsychiatric events were reported more frequently in patients being treated with FYCOMPA than in patients taking placebo. These events included irritability, aggression, anger, and anxiety, which occurred in 2% or greater of FYCOMPA-treated patients and twice as frequently as in placebo-treated patients. Other symptoms that occurred with FYCOMPA and were more common than with placebo included belligerence, affect lability, agitation, and physical assault. Some of these events were reported as serious and life-threatening. Homicidal ideation and/or threat were exhibited in 0.1% of 4,368 FYCOMPA-treated patients in controlled and open label trials, including non-epilepsy trials. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. In the partial-onset seizure clinical trials, these events occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. Some patients experienced worsening of their pre-existing psychiatric conditions. Patients with active psychotic disorders and unstable recurrent affective disorders were excluded from the clinical trials. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic seizure clinical trial. In healthy volunteers taking FYCOMPA, observed psychiatric events included paranoia, euphoric mood, agitation, anger, mental status changes, and disorientation/confusional state. In the non-epilepsy trials, psychiatric events that occurred in perampanel-treated patients more often than placebo-treated patients included disorientation, delusion, and paranoia. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least 1 month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Dose of FYCOMPA should be reduced if these symptoms occur. Permanently discontinue FYCOMPA for persistent severe or worsening psychiatric symptoms or behaviors and refer for psychiatric evaluation. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1. Risk by indication for antiepileptic drugs in the pooled analysis Indication
Placebo Patients with Events per 1000 Patients
Drug Patients with Events per 1000 Patients
Epilepsy Psychiatric Other Total
1.0 5.7 1.0 2.4
3.4 8.5 1.8 4.3
Relative Risk: Incidence of Events in Drug Patients/ Incidence in Placebo Patients 3.5 1.5 1.9 1.8
Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4 2.9 0.9 1.9
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Neurologic Effects Dizziness and Gait Disturbance FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. In the controlled partial-onset seizure clinical trials, dizziness and vertigo were reported in 35% and 47% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. The gait disturbance related events (including ataxia, gait disturbance, balance disorder, and abnormal coordination) were reported in 12% and 16% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. Elderly patients had an increased risk of these adverse reactions compared to younger adults and pediatric patients. These adverse reactions occurred mostly during the titration phase and led to discontinuation in 3% of FYCOMPA-treated patients compared to 1% of placebo-treated patients. These
adverse reactions were also observed in the primary generalized tonic-clonic seizure clinical trial. Somnolence and Fatigue FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events (including fatigue, asthenia, and lethargy). In the controlled partial-onset seizure clinical trials, 16% and 18% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, reported somnolence compared to 7% of placebo patients. In the controlled partial-onset seizure clinical trials, 12% and 15% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, reported fatigue-related events compared to 5% of placebo patients. Somnolence or fatiguerelated events led to discontinuation in 2% of FYCOMPA-treated patients and 0.5% of placebo-treated patients. Elderly patients had an increased risk of these adverse reactions compared to younger adults and pediatric patients. In the controlled partial-onset seizure clinical trials, these adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the primary generalized tonic-clonic seizure clinical trial. Risk Amelioration Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known. Falls An increased risk of falls, in some cases leading to serious injuries including head injuries and bone fracture, occurred in patients being treated with FYCOMPA (with and without concurrent seizures). In the controlled partial-onset seizure clinical trials, falls were reported in 5% and 10% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients. Falls were reported as serious and led to discontinuation more frequently in FYCOMPA-treated patients than placebo-treated patients. Elderly patients had an increased risk of falls compared to younger adults and pediatric patients. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including FYCOMPA. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. FYCOMPA should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Withdrawal of Antiepileptic Drugs There is the potential of increased seizure frequency in patients with seizure disorders when antiepileptic drugs are withdrawn abruptly. FYCOMPA has a half-life of approximately 105 hours so that even after abrupt cessation, blood levels fall gradually. In epilepsy clinical trials FYCOMPA was withdrawn without down-titration. Although a small number of patients exhibited seizures following discontinuation, the data were not sufficient to allow any recommendations regarding appropriate withdrawal regimens. A gradual withdrawal is generally recommended with antiepileptic drugs, but if withdrawal is a response to adverse events, prompt withdrawal can be considered. ADVERSE REACTIONS 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 clinical practice. Partial-Onset Seizures Adult and Adolescent Patients (≥12 years) A total of 1,038 patients receiving FYCOMPA (2, 4, 8, or 12 mg once daily) constituted the safety population in the pooled analysis of the placebo-controlled trials (Studies 1, 2, and 3) in patients with partial-onset seizures. Approximately 51% of patients were female, and the mean age was 35 years. Adverse Reactions Leading to Discontinuation In controlled clinical trials (Studies 1, 2, and 3), the rate of discontinuation as a result of an adverse reaction was 3%, 8%, and 19% in patients randomized to receive FYCOMPA at the recommended doses of 4 mg, 8 mg, and 12 mg per day, respectively, and 5% in patients randomized to receive placebo. The adverse reactions most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg FYCOMPA group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria. Most Common Adverse Reactions Table 2 gives the incidence in the controlled clinical trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in the FYCOMPA 12 mg dose group and more frequent than placebo (in order of decreasing frequency for the 12 mg dose group). The most common dose-related adverse reactions in patients receiving FYCOMPA at doses of 8 mg or 12 mg (≥4% and occurring at least 1% higher than the placebo group) included dizziness (36%), somnolence (16%), fatigue (10%), irritability (9%), falls (7%), nausea (7%), ataxia (5%), balance disorder (4%), gait disturbance (4%), vertigo (4%), and weight gain (4%). For almost every adverse reaction, rates were higher on 12 mg and more often led to dose reduction or discontinuation. Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in Adult and Adolescent Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent than Placebo) Placebo n=442 % Dizziness Somnolence Headache Irritability Fatigue Falls Ataxia Nausea Vertigo Back pain Dysarthria Anxiety Blurred vision Gait disturbance Weight gain Cough Upper respiratory tract infection Vomiting Hypersomnia Anger Aggression Balance disorder Diplopia Head injury Hypoaesthesia Pain in extremity Constipation Myalgia Coordination abnormal Euphoric mood Confusional state Hyponatremia
9 7 11 3 5 3 0 5 1 2 0 1 1 1 1 3 3 3 0 <1 1 1 1 1 1 1 2 2 0 0 <1 <1
4 mg n=172 % 16 9 11 4 8 2 1 3 4 2 1 2 1 1 4 1 3 2 1 0 1 0 1 1 0 0 2 1 1 0 1 0
FYCOMPA 8 mg n=431 % 32 16 11 7 8 5 3 6 3 2 3 3 3 4 4 1 3 3 2 1 2 5 1 1 0 2 2 1 <1 <1 1 0
12 mg n=255 % 43 18 13 12 12 10 8 8 5 5 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 3 3 3 2 2 2 2
Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in Adult and Adolescent Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent than Placebo) (cont.) Limb injury Mood altered Arthralgia Asthenia Contusion Memory impairment Musculoskeletal pain Oropharyngeal pain Paraesthesia Peripheral edema Skin laceration
<1 <1 1 1 1 1 1 1 1 1 1
1 1 0 1 0 0 1 2 0 1 0
1 <1 3 2 2 1 1 2 1 1 2
2 2 2 2 2 2 2 2 2 2 2
Pediatric Patients (4 to <12 years) In two studies in pediatric patients 4 to <12 years with epilepsy, a total of 225 patients received FYCOMPA, with 110 patients exposed for at least 6 months, and 21 patients for at least 1 year. Adverse reactions in pediatric patients 4 to <12 years were similar to those seen in patients ≥12 years Primary Generalized Tonic-Clonic Seizures A total of 81 patients receiving FYCOMPA 8 mg once daily constituted the safety population in the placebo-controlled trial in patients with primary generalized tonicclonic seizures (Study 4). Approximately 57% of patients were female, and the mean age was 27 years. In the controlled primary generalized tonic-clonic seizure clinical trial (Study 4), the adverse reaction profile was similar to that noted for the controlled partial-onset seizure clinical trials (Studies 1, 2, and 3). Table 3 gives the incidence of adverse reactions in patients receiving FYCOMPA 8 mg (≥4% and higher than in the placebo group) in Study 4. The most common adverse reactions in patients receiving FYCOMPA (≥10% and greater than placebo) were dizziness (32%), fatigue (15%), headache (12%), somnolence (11%), and irritability (11%). The adverse reactions most commonly leading to discontinuation in patients receiving FYCOMPA 8 mg (≥2% and greater than placebo) were vomiting (2%) and dizziness (2%). Table 3. Adverse Reactions in a Placebo-Controlled Trial in Patients with Primary Generalized Tonic-Clonic Seizures (Study 4) (Reactions ≥ 4% of Patients in FYCOMPA Group and More Frequent than Placebo)
Dizziness Fatigue Headache Somnolence Irritability Vertigo Vomiting Weight gain Contusion Nausea Abdominal pain Anxiety Urinary tract infection Ligament sprain Balance disorder Rash
Placebo n=82 % 6 6 10 4 2 2 2 4 4 5 1 4 1 0 1 1
FYCOMPA 8 mg n=81 % 32 15 12 11 11 9 9 7 6 6 5 5 4 4 4 4
Weight Gain Weight gain has occurred with FYCOMPA. In controlled partial-onset seizure clinical trials, FYCOMPA-treated adults gained an average of 1.1 kg (2.5 lbs) compared to an average of 0.3 kg (0.7 lbs) in placebo-treated adults with a median exposure of 19 weeks. The percentages of adults who gained at least 7% and 15% of their baseline body weight in FYCOMPA-treated patients were 9.1% and 0.9%, respectively, as compared to 4.5% and 0.2% of placebo-treated patients, respectively. Clinical monitoring of weight is recommended. Similar increases in weight were also observed in adult and adolescent patients treated with FYCOMPA in the primary generalized tonic-clonic seizure clinical trial. Elevated triglycerides Increases in triglycerides have occurred with FYCOMPA use. Comparison of Sex and Race No significant sex differences were noted in the incidence of adverse reactions. Although there were few non-Caucasian patients, no differences in the incidence of adverse reactions compared to Caucasian patients were observed. Postmarketing Experience The following adverse reactions have been identified during post approval use of FYCOMPA. 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. Dermatologic: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Psychiatric: Acute psychosis, hallucinations, delusions, paranoia, delirium, confusional state, disorientation, memory impairment. DRUG INTERACTIONS Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40%. Use of FYCOMPA with contraceptives containing levonorgestrel may render them less effective. Additional non-hormonal forms of contraception are recommended. Moderate and Strong CYP3A4 Inducers The concomitant use of known moderate and strong CYP3A4 inducers including carbamazepine, phenytoin, or oxcarbazepine with FYCOMPA decreased the plasma levels of perampanel by approximately 50-67%. The starting doses for FYCOMPA should be increased in the presence of moderate or strong CYP3A4 inducers. When these moderate or strong CYP3A4 inducers are introduced or withdrawn from a patient’s treatment regimen, the patient should be closely monitored for clinical response and tolerability. Dose adjustment of FYCOMPA may be necessary. Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. A pharmacodynamic interaction study in healthy subjects found that the effects of FYCOMPA on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol. Multiple dosing of FYCOMPA 12 mg per day also enhanced the effects of alcohol to interfere with vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. Care should be taken when administering FYCOMPA with these agents. Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). Advise patients not to drive or operate machinery until they have gained sufficient experience on FYCOMPA to gauge whether it adversely affects these activities. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FYCOMPA, during pregnancy. Encourage women who are taking FYCOMPA during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk summary There are no adequate data on the developmental risk associated with use in pregnant women. In animal studies, perampanel induced developmental toxicity in pregnant rat and rabbit at clinically relevant doses. 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. Animal Data Oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in an increase in visceral abnormalities (diverticulum of the intestine) at all doses tested; maternal toxicity was observed at the mid and high doses. In a dose-ranging study at higher oral doses (10, 30, or 60 mg/kg/day), embryo lethality and reduced fetal body weight were observed at the mid and high doses tested.The lowes tdose tested (1mg/kg/day) is similar to a human dose of 8 mg/day based on body surface area (mg/m2). Upon oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rabbits throughout organogenesis, embryo lethality and maternal toxicity were observed at the mid and high doses tested; the no-effect dose for embryo-fetal developmental toxicity in rabbit (1mg/kg/day) is approximately 2 times a human dose of 8mg/day based on body surface area (mg/m2). Oral administration of perampanel (1, 3, or 10 mg/kg/day) to rats throughout gestation and lactation resulted in fetal and pup deaths at the mid and high doses (associated with maternal toxicity) and delayed sexual maturation in males and females at the highest dose tested. No effects were observed on measures of neurobehavioral or reproductive function in the offspring. The no-effect dose for pre- and postnatal developmental toxicity in rat (1 mg/kg/day) is similar to a human dose of 8 mg per day based on body surface area (mg/m2). Lactation Risk summary There are no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Perampanel and/or its metabolites are excreted in rat milk, and are detected at concentrations higher than that in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FYCOMPA and any potential adverse effects on the breastfed child from FYCOMPA or from the underlying maternal condition. Females and Males of Reproductive Potential Contraception Use of FYCOMPA may reduce the efficacy of hormonal contraceptives containing levonorgestrel. Advise women taking FYCOMPA who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form of contraception while using FYCOMPA and for a month after discontinuation. Pediatric Use Safety and effectiveness of FYCOMPA for the treatment of partial-onset seizures have been established in pediatric patients ≥4 years. The safety and effectiveness of FYCOMPA in patients ≥12 years was established by three randomized double-blind, placebo-controlled, multicenter studies, which included 72 pediatric patients between 12 and 16 years exposed to FYCOMPA. Use of FYCOMPA for the treatment of partial-onset seizures in pediatric patients 4 to <12 years is supported by evidence from adequate and well-controlled studies of FYCOMPA in patients aged ≥12 years with partial onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 225 pediatric patients 4 to <12 years treated with FYCOMPA. The safety and efficacy of FYCOMPA for the adjunctive therapy of primary generalized tonic-clonic seizures in pediatric patients ≥12 years was established in a single randomized double-blind, placebo-controlled, multicenter trial (n=164), which included 11 pediatric patients 12 to 16 years exposed to FYCOMPA; an additional 6 patients were treated with FYCOMPA in the open label extension of the study. The safety and effectiveness of FYCOMPA for the treatment of partial-onset seizures in pediatric patients <4 years or for the treatment of primary generalized tonicclonic seizures in pediatric patients <12 years have not been established. Juvenile Animal Data Oral administration of perampanel (1, 3, 3/10/30 mg/kg/day; high dose increased on postnatal days [PND] 28 and 56) to young rats for 12 weeks starting on PND 7 resulted in reduced body weight, reduced growth, neurobehavioral impairment (water maze performance and auditory startle habituation) at the mid and high doses, and delayed sexual maturation at the high doses. CNS signs (reduced activity, incoordination, excessive grooming/scratching), pup death, decreased hindlimb splay, and decreased hindlimb grip strength were observed at all doses. Effects on pup body weight, pup growth, hindlimb splay, impairment in the water maze performance, and auditory startle persisted after dosing was stopped. A no-effect dose for postnatal developmental toxicity was not identified in this study. Oral administration of perampanel (1, 5,5/10 mg/kg/day; high dose increased on PND 56) to juvenile dogs for 33 weeks, starting on PND 42, resulted in CNS signs (incoordination, excessive grooming/licking/scratching, spatial disorientation, and/or ataxic gait) at all doses tested. Geriatric Use Clinical studies of FYCOMPA did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of FYCOMPA in the elderly population. Because of increased likelihood for adverse reactions in the elderly, dosing titration should proceed slowly in patients aged 65 years and older. Hepatic Impairment Use of FYCOMPA in patients with severe hepatic impairment is not recommended, and dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Renal Impairment Dose adjustment is not required in patients with mild renal impairment. FYCOMPA should be used with caution in patients with moderate renal impairment, and slower titration may be considered. Use in patients with severe renal impairment or patients undergoing hemodialysis is not recommended. DRUG ABUSE AND DEPENDENCE Controlled Substance FYCOMPA contains perampanel and is listed as a Schedule III controlled substance. Abuse Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, for its rewarding psychological or physiological effects. Drug addiction, which develops after repeated drug abuse, is characterized by a strong desire to take a drug despite harmful consequences, difficulty in controlling its use, giving a higher priority to drug use than to obligations, increased tolerance, and sometimes physical withdrawal. Drug abuse and drug addiction are separate and distinct from physical dependence (for example, abuse may not be accompanied by physical dependence). Studies of human abuse potential were performed to evaluate the abuse potential of FYCOMPA (8 mg, 24 mg, and 36 mg) as compared to alprazolam C-IV (1.5 mg and 3 mg), and oral ketamine C-III (100 mg) in recreational polydrug users. Supra-therapeutic doses of FYCOMPA 24 and 36 mg produced responses for “Euphoria” that were similar to ketamine 100 mg and alprazolam 3 mg. For “High,” FYCOMPA 24 mg and 36 mg produced responses comparable to ketamine 100 mg and significantly higher than both doses of alprazolam on a visual analog scale (VAS). “Drug Liking,” “Overall Drug Liking,” and “Take Drug Again” for FYCOMPA were each statistically lower than ketamine 100 mg. In addition, for “Bad Drug Effects,” FYCOMPA 24 mg and 36 mg produced responses significantly higher than ketamine 100 mg. For “Sedation,” FYCOMPA 24 and 36 mg produced responses similar to alprazolam 3 mg and higher than ketamine 100 mg. Additionally, on VAS measures related to dissociative phenomena such as “Floating,” “Spaced Out,” and “Detached,” FYCOMPA at supra-therapeutic doses produced responses similar to ketamine 100 mg and greater than both doses of alprazolam tested. Of note, due to somnolence a number of subjects had missing data around Tmax of FYCOMPA. The above described data might represent an underestimate of FYCOMPA’s effects. The duration of effects of higher doses of FYCOMPA on the majority of measures was much greater than alprazolam 3 mg and ketamine 100 mg. In this study, the incidence of euphoria following FYCOMPA administration 8 mg, 24 mg, and 36 mg was 37%, 46%, 46%, respectively, which was higher than alprazolam 3 mg (13%) but lower than ketamine 100 mg (89%). Dependence Physical dependence is characterized by withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. A nonclinical dependence study in rats demonstrated withdrawal symptoms, including hyperreactivity to handling, muscle rigidity, and decreases in food consumption and body weights. FYCOMPA may cause dependence and withdrawal symptoms that may include anxiety, nervousness, irritability, fatigue, lethargy, asthenia, mood swings, and insomnia. OVERDOSAGE There is limited clinical experience with FYCOMPA overdose. The highest reported overdose (approximately 264 mg) was intentional. This patient experienced serious adverse reactions of altered mental status, agitation, and aggressive behavior and recovered without sequelae. In general, the adverse reactions associated with overdoses were similar to the reactions at therapeutic doses with dizziness reported most frequently. There were no reported sequelae. There is no available specific antidote to the overdose reactions of FYCOMPA. In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with FYCOMPA. Due to its long half-life, the reactions caused by FYCOMPA could be prolonged.
FYCOMPA® is a registered trademark of Eisai R&D Management CO., Ltd., licensed to Eisai Inc. ©2018 Eisai Inc. FYCO-US2484 October 2018
Vote on Board Nominees at Today’s Business Meeting Continued from cover The current President Elect, James C. Stevens, MD, FAAN, will begin his term as President on May 11, 2019. The current President, Ralph L. Sacco, MD, MS, FAHA, FAAN, will then serve on the Board of Directors as Immediate Past President.
OFFICERS: President Elect
Vice President
Secretary
Treasurer
Brenda Banwell, MD, FAAN
Sarah M. Benish, MD, FAAN
Charlene Gamaldo, MD, FAAN
James N. Goldenberg, MD, FAAN
Elaine C. Jones, MD, FAAN
Shannon M. Kilgore, MD, FAAN
Brett M. Kissela, MD, MS, FAAN
Thomas R. Vidic, MD, FAAN
Orly Avitzur, MD, MBA, FAAN
Ann H. Tilton, MD, FAAN
Carlayne E. Jackson, MD, FAAN
Janis M. Miyasaki, MD, MEd, FRCPC, FAAN
DIRECTORS:
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Jonathan P. Hosey, MD, FAAN
The following additional directors will serve ex officio beginning beginning on May 11: Nicholas E. Johnson, MD, FAAN, Chair, Advocacy Committee (ex officio)
Brad C. Klein, MD, MBA, FAAN, Chair, Medical Economics and Practice Committee (ex officio)
Gregory D. Cascino, MD, FAAN, Chair, Member Engagement Committee (ex officio)
Robert A. Gross, MD, PhD, FAAN, Editor-in-Chief of Neurology ® (ex officio]
Catherine M. Rydell, CAE, Chief Executive Officer (ex officio, non-voting)
The Academy is comprised of two legal entities, the AAN and the AAN Institute. Most of the elected members of the AAN Board of Directors also serve ex officio on the Board of Directors of the AAN Institute, which includes an independent secretary-treasurer and additional members who serve in ex officio capacities. The AAN Institute Board of Directors includes the following additional members: Charles C. Flippen II, MD, FAAN, AAN Institute Secretary-Treasurer
Natalia S. Rost, MD, MPH, FAAN, FAHA, Chair, Science Committee (ex officio)
Lyell K. Jones, Jr., MD, FAAN, Chair, Quality Committee (ex officio)
A. Gordon Smith, MD, FAAN, Chair, Education Committee (ex officio)
Visit AAN.com/view/BOD to see the full slate of candidates and their bios.
DeAngelis to Receive President’s Award Lisa M. DeAngelis, MD, FAAN, has been selected by President Ralph L. Sacco, MD, MA, FAHA, FAAN, to receive the President’s Award for 2019.
and twice on the AAN Board of Directors. She has strengthened the AAN’s efforts for science by advancing our engagement with the NIH and other organizations. She also led the AAN’s Diversity Leadership Task Force. Given these multiple major contributions to advancing the AAN mission, Lisa is an exemplary leader and role model, and fully deserving of the 2019 President’s Award for her outstanding service to the AAN.”
Citing a few of her many accomplishments, Sacco said, “Dr. DeAngelis is chair of the department of neurology at Memorial Sloan DeAngelis Kettering Cancer Center, where she holds the Lillian Rojtman Berkman Chair in honor of Dr. Jerome Posner and is currently acting physician DeAngelis will receive the award during the Presidential in chief. She has published extensively on a wide variety Plenary Session on May 5. of topics in neuro-oncology and is particularly known for developing the current standard regimen to treat primary CNS lymphoma, the first brain tumor to be treated with chemotherapy exclusively. Lisa’s efforts have forever changed the strategic direction of our organization. She has served on numerous subcommittees and committees
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Build and Expand Your Leadership Potential Throughout the Week No matter what your career stage, you’ll find unique opportunities throughout the week that are designed to help you take your career to the next level. Each program is based in a leadership fundamental and led by a world-renowned consultant and/or physician leader in the field of neurology. Look for courses tailored specifically for women or those focused on leadership challenges in practice, as well as for anyone who simply wants to gain a deeper understanding of their strengths and how to use them to work more effectively. Note that some of these courses require advance registration. Visit AAN.com/view/LeadershipUniversity to learn more.
Women in Leadership: Empowering the Leader Within You Saturday, May 4 7:00 a.m.–3:30 p.m. Directors: Janice M. Massey, MD, FAAN; Orly Avitzur, MD, MBA, FAAN; and Keri Bischoff and Julie Anderson, Gallup-certified Strengths Consultants
Avitzur
Bischoff
Leadership Challenges in Practice
Chief Resident Leadership Program
Saturday, May 4 12:00 p.m.–4:00 p.m.
Sunday, May 5 12:00 p.m.–4:00 p.m.
Director: Brad C. Klein, MD, MBA, FAAN This program will discuss several critical leadership skills, including Klein understanding and implementing varying communication approaches to effect change internally within an organization, addressing internal practice challenges, and discussing practical approaches to improve personal growth, professional fulfillment, and physician well-being while still improving the bottom line. Included with meeting registration.
Massey
Anderson
This session will begin by revealing participants' unique leadership style. Through conversations and guided exercises, participants will create a customized Strengths-based Leadership Statement: your guide to be the best leader you can be. Presenters will also address common experiences, challenges and leadership issues such as negotiation skills and burnout, using the personal stories of women in neurology. Advance registration required. Visit the Registration desk to check availability.
Educators' Leadership Program Saturday, May 4 / 1:30 p.m.–4:00 p.m. Director: Rana R. Said, MD Neurology clerkship and program directors are among the most important gatekeepers of our pipeline Said to careers in neurology. In many cases, these education leaders are responsible for the first contact with potential candidates for the future neurology workforce. This program is designed to optimize the skill set of program/clerkship directors and associate program/clerkship directors who have been in their roles three to 10 years. Advance application required.
Director: Maisha T. Robinson, MD, MS In this program, current and future neurology chief residents will explore their Robinson own leadership potential, learn skills to enhance their success in their leadership role, and develop critical skills for use in this and future leadership roles. Included with meeting registration.
Women in Leadership: 2019, Why Are We Still Talking About This? Sunday, May 5 1:00 p.m.–4:00 p.m. Director: Laraine Kaminsky, CEO, Global LK While the rates of women in medicine have grown steadily over the last Kaminsky century, they tend to be concentrated in specialties such as pediatrics and OB/GYN and are underrepresented in other disciplines, including neurology. Evidence shows that gender diversity contributes to improved performance and effectiveness within organizations, yet there remain many systemic, organizational, and cultural barriers to women's participation and inclusion in the workplace. This presentation will draw on current and relevant research and examples to explore opportunities for women in leadership in the global workplace and marketplace. Included with meeting registration.
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Leadership in the Era of Burnout: A Practical Approach to Becoming a True Physician Leader Monday, May 6 1:00 p.m.–4:00 p.m. Director: Terrence L. Cascino, MD, FAAN
Cascino
The challenge of being a leader is complicated by a high rate of burnout. This course will examine how to lead effectively while promoting wellness.
Included with meeting registration.
Mitigating the Impact of Unconscious Bias Tuesday, May 7 1:00 p.m.–4:00 p.m. Director: Laraine Kaminsky, CEO, Global LK During this informative, participatory, and engaging workshop, faculty will explore the science of unconscious bias, with a specific focus on the impact of bias and resulting disparities in the health care sector.
Strengths Spotting: Using Strengths to Help Improve Communication with Patients, Colleagues, and Leaders Tuesday, May 1:00 p.m.–5:00 p.m. Directors: Keri Bischoff and Julie Anderson, Gallup-certified Strengths Consultants An awareness of what is right about others, a practice known as Strengths Spotting, is one of the best ways to deepen your understanding of your strengths and the strengths of others. Through interactive and guided discussions, the presenters will share tools to improve relationships and increase productivity, ultimately improving patient care by maximizing their experience. Advance registration required. Visit the Registration desk to check availability.
The Doctors’ Lounge Helping Physicians in Mid-career Renew and Repurpose Their Work/Lives Tuesday, May 7 1:00 p.m.–4:00 p.m.
This workshop is designed to help physicians at midlife answer the question "What's next?" It will provide the seasoned guidance and map plus peer network to help physicians figure out what they want to happen in the next phase of their work/ lives. Richard Leider is one of America’s preeminent executive-life coaches. Advance registration required. Visit the Registration desk to check availability.
Team Building in Medicine: How to Incorporate Strengths Training into Medical Teams Wednesday, May 8 1:00 p.m.–5:00 p.m. Directors: Keri Bischoff and Julie Anderson, Gallup-certified Strengths Consultants During this workshop attendees will learn a step-by-step approach to building a strengths-based team by understanding, appreciating, and investing in the unique talents of everyone involved. Advance registration required. Visit the Registration desk to check availability.
Directors: Terrence L. Cascino, MD, FAAN, and Richard Leider, founder of Inventure—The Purpose Company
Included with meeting registration.
Leider
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Spanish-language Programs Cover Wide Range of Topics Look for education courses, scientific updates, and experiential learning area talks throughout the week that will be presented entirely in Spanish and cover a wide range of topics including MS, teleneurology, transnational research opportunities, and the challenges and opportunities of different career paths in neurology. New this year, the Almuerzo con Colegas provide opportunities for Spanishspeaking attendees from around the world to discuss common issues over lunch. Encontrará cursos educativos, actualizaciones científicas y charlas en el área de aprendizaje empírico sobre una amplia variedad de temas, que incluyen la EM, teleneurología, oportunidades transnacionales de investigación y retos y posibilidades de distintas trayectorias profesionales en la rama de la neurología. Nuevo este año, durante Almuerzo con Colegas, nos reuniremos a comer con colegas hispanoparlantes para charlar sobre temas de interés común.
Saturday Teleneurología (Teleneurology) / 1:30 p.m.–3:30 p.m.
Sunday C46: Actualización en dolor de cabeza y trastornos neuro
musculares (Update: Headache and Neuromuscular Disorder) / 7:00 a.m.–9:00 a.m.
Almuerzo con Colegas: Perlas clínicas / Solicitando
una residencia o subespecialidad en neurología (Lunch with Colleagues: Clinical Pearls / Finding a Residency or Fellowship in Neurology) / 12:00 p.m.–12:45 p.m.
C59: Cuidados neurocríticos (Neurocritical Care) /
1:00 p.m.–3:00 p.m.
Monday Almuerzo con Colegas: Neurología general /
Investigaciones clínicas (Lunch with Colleagues: General Neurology / Clinical Trials) / 12:00 p.m.–12:45 p.m.
C100: Esclerosis múltiple y otras enfermedades
inflamatorias desmielinizantes y autoinmunes del sistema nervioso central (MS and Other Demyelinating Inflammatory and Autoimmune Central Nervous System Disorders) / 1:00 p.m.–3:00 p.m.
Lost in Translation: Acknowledging and Respecting
Cultural Differences with Your Patients (Presented in English) / 3:00 p.m.–3:45 p.m.
C119: Actualización en lesión cerebral traumática e ictus
isquémico (Update: TBI and Stroke) / 3:30 p.m.–5:30 p.m.
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Tuesday Almuerzo con Colegas: Trombectomía en ictus / Consejos
para obtener empleo en USA: opciones clínicas y extraclínicas (Lunch with Colleagues: Stroke / Job search in the USA: Clinical and non-clinical) / 12:00 p.m.–12:45 p.m.
C144: Actualización científica I (Scientific Update I—Spanish) /
1:00 p.m.–3:00 p.m.
Oportunidades de colaboración internacional para
realizar proyectos de investigación en enfermedades neurodegenerativas (Opportunities for International Collaborations to Conduct Research on Neurodegenerative Diseases) / 3:00 p.m.–3:45 p.m.
Wednesday Consejos prácticos para educadores médicos
(Practical Advice for Medical Educators) / 8:00 a.m.–8:45 p.m.
C185: Actualización en trastornos del movimiento
(Update in Movement Disorders) / 1:00 p.m.–3:00 p.m.
Perspectivas profesionales para neurólogos en los Estados
Unidos y América Latina (Professional Perspective for Neurologists in the United States and Latin America) / 5:00 p.m.–5:45 p.m.
Thursday C225: Actualización científica II (Scientific Update II) /
1:00 p.m.–3:00 p.m.
Consejos prácticos para un buen examen neurológico
(Neuro Exam Tips and Tricks) / 3:00 p.m.–4:00 p.m.
INDUSTRY THERAPEUTIC UPDATE FROM AVEXIS A NEW FRONTIER FOR NEUROMUSCULAR DISORDERS: SPOTLIGHT ON GENE THERAPY Wednesday May 8 2019, 7:00 PM for 7:30 PM start* Room: Liberty Ballroom, Philadelphia Marriott Downtown
Faculty:
Perry Shieh, MD, PhD (Chair) Meredith Schultz, MD Christopher Walker, PhD Chris Jenkins, PhD *Dinner to be served at 7:00 PM
The Faculty of experts will explore the latest advances in gene therapy (GT) research and the use of GT in the clinical treatment of neuromuscular diseases, taking the treatment from bench to bedside. Time
Presentation Title
Faculty Member
7:00 – 7:30 PM
Dinner reception
7:30 – 7:35 PM
Welcome and introduction
Perry Shieh, MD, PhD (Chair)
7:35 – 7:55 PM
Gene therapies: a new frontier for neuromuscular disorders
Meredith Schultz, MD
7:55 – 8:15 PM
A focus on adeno-associated virus (AAV) antibodies
Christopher Walker, PhD
8:15 – 8:35 PM
Biosafety considerations for the clinical use of AAVs
Chris Jenkins, PhD
8:35 – 8:45 PM
Panel discussion
All Speakers Facilitated by Chair
8:45 – 8:55 PM
Questions and answers
All Speakers Facilitated by Chair
8:55 – 9:00 PM
Closing remarks
Perry Shieh, MD, PhD (Chair)
In accordance with Federal Law, all food and beverage are reportable. You will have the opportunity to opt-out of food and beverage upon arrival at the Liberty Ballroom, Philadelphia Marriott Downtown This meeting is not part of the AAN Annual Meeting official programming and no CME is given for attendance. This Industry Therapeutic Update is sponsored and organized by AveXis. ©2019 AveXis, Inc. All Rights Reserved.
MED-CON-UNB-00019-US 04/2019
Visit the Networking and Innovation Space to Discover the AAN’s Robust eLearning Opportunities
New Academic Neurology Room Offers Hub for Resources, Team Building, More
Visit the eLearning Networking and Innovation Space in the Arch Street Atrium throughout the week to learn about the AAN’s robust lineup of eLearning products.
As part of its ongoing commitment to support academic neurologists across their professional lifetimes and address the current and future needs of academic neurology departments, the Annual Meeting will offer a special hub designed specifically for academic neurologists. Located in Room Sacco 202 AB of the Pennsylvania Convention Center, the Academic Neurology Room will offer a unique space for academic neurologists across all career roles and stages to come together to experience a variety of opportunities focused on faculty development, leadership, research, team building, career development, communication improvement, and more.
While at this one-stop-shop for all things eLearning, you can purchase your copy of Annual Meeting On Demand and pick up your complimentary earbuds; view the exciting new NeuroBytes educational videos; see demos of NeuroSAE, NeuroLearn, the Neurology MOC Prep Course, and new Neurology Board Prep Course; and more—all available from the AAN’s convenient Online Learning Center. Relax and catch up with colleagues in the comfortable lounge space, provide feedback on the NeuroBytes videos, and be entered into a drawing for a chance to win a portable power bank or Annual Meeting On Demand subscription. Let us know that you’re interested in helping create new programs by serving as a content expert, item writer, or tester. Staff will be on hand to answer all your questions and to listen and ideate on new eLearning program opportunities.
In addition to hosting many of the programs within the official Academic Medicine Track—which can be searched easily by filtering with the words “Academic Medicine Track” within your AAN Conferences App—the room will serve as a weeklong destination for a variety of other programs and opportunities including Division Chief's Round Table: Maximizing Effectiveness and Addressing Challenges; Access: Strategies to Improve Access in Academic Medicine; Creating a Roadmap for a Diverse Workforce in Academic Neurology; Business Efficiencies for Academic Neurology Departments: Business Strategies for Success; Academic Neurology Departments 2020 and Beyond: Succeeding in the Tripartite Mission; and Faculty Development: Enhancing Your Role in Student and Resident Training, and many more. In addition, check out the offerings for academicians all week long in the Grand Experience, located in the Grand Hall of the convention center. “Academic neurology departments face many challenges today, including health care reform, research funding cuts, neurology work force issues, graduate medical education funding cuts, reduced reimbursement for services, and increasing regulatory burden,” said AAN President Ralph L. Sacco, MD, MS, FAHA, FAAN. “Thus, it is imperative to comprehensively examine the needs of academic neurology departments and develop tangible solutions in collaboration with chairs and academic administrators to advance the future of academic neurology, which is critical to the field of neurology, neuroscience, patients, trainees, and the AAN.”
28
Saturday, May 4, 2019 • AANextra
What Excited You Today at #AANAM?
Join the conversation at #AANAM Elissa Fory @ekfory So excited to be packing for #AANAM. I may or may not have gone overboard. #WearYourGreen #ILookLikeANeurologist #GreenBowRedefined #WomenInMedicine @stephanamayer
Ilene Ruhoy, MD, PhD @MdRuhoy
Discussing #physicianburnout , especially #neurologist burnout, all day at the #AANAM . Community is important. Donâ&#x20AC;&#x2122;t hesitate to just reach out. Take a chance on your colleague.
Bert Vargas @BertVargas
Shirts: Shoes: Suits: SPG block demo head: Prop championship belt: How do YOU pack for #AANAM? @aanbrain #NeuroZone
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AAN Calls for Uniformity of Brain Death Determination The AAN is calling for uniform brain death laws, policies, and practices in a new position statement published in the January 2, 2019, online issue of Neurology ® at Neurology.org. The position statement is endorsed by the American Neurological Association and the Child Neurology Society.
life care,” said position statement author James A. Russell, DO, MS, FAAN, of Lahey Hospital and Medical Center in Burlington, MA, and chair of the Ethics, Law and Humanities Committee. “The AAN supports the development of legislation in every state modeled after the Nevada statute, which specifically defers to these current adult and pediatric brain death guidelines and any future updates.”
Brain death is defined as the death of the individual due Russell to irreversible loss of function to the entire brain. It is the The AAN position statement also calls for uniform equivalent of circulatory death, which is due to irreversible policies in medical facilities across the country that would ensure loss of function of the circulatory system, which includes the heart. compliance to the brain death guidelines. The brain death standards for adults and children that are widely “The lack of specificity in most states’ laws, coupled with accepted by the medical profession are these two guidelines: the inconsistency among brain death protocols in medical facilities, AAN’s 2010 Evidence-based Guideline Update: Determining Brain has contributed to differing interpretations by the courts in a few Death in Adults and the 2011 Guidelines for the Determination of high-profile cases,” said Russell. “The AAN wants the general Brain Death in Infants and Children, published by the Pediatric public to know that when these guidelines are followed, the result Section of the Society of Critical Care Medicine, the Sections is an accurate determination of brain death.” of Neurology and Critical Care of the American Academy of Pediatrics, and the Child Neurology Society. The position statement also supports the development of programs that train and credential physicians that determine death by The AAN is not aware of any cases in which following these neurologic criteria and that provide public and professional guidelines led to inaccurate determination of death with return education regarding brain death and its determination. of any brain function, including consciousness, brainstem reflexes, or breathing. Yet only the state of Nevada has adopted Recognizing that each case is unique, the AAN position statement legislation that requires using these widely accepted brain death also provides guidance to medical professionals when a family guidelines as the medical standard, as authorized by the Uniform may not accept a determination of death of their loved one due to Determination of Death Act, for the determination of brain death. religious, moral, or cultural reasons, and requests continued life support. The position statement states that continuing to provide “The AAN believes that a specific, uniform standard for the life support when a person is dead may deprive that person of determination of brain death is critically important to provide dignity or provide false hope to the family. the highest quality patient-centered neurologic and end-of-
LEARN ABOUT A NEW ORAL TREATMENT FOR MULTIPLE SCLEROSIS Visit Booth ©2019 EMD Serono, Inc. All rights reserved. Printed in the USA US/NPR/0319/0198 03/19
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Today’s Inspiring and Innovative New Talk to Explore Bionics The first in a new series of Annual Meeting programming will kick off today at 5:45 p.m. in the Terrace Ballroom with Hugh Herr, PhD, leading a fascinating talk on The New Era of Extreme Bionics. Herr, who heads the Biomechatronics group at the MIT Media Lab, is creating bionic limbs that emulate the function of natural limbs. In 2011, TIME magazine coined him the “Leader of the Bionic Age” because of his revolutionary work in the emerging field of biomechatronics technology that marries human physiology with electromechanics. Free food and beverages will be available immediately following Herr’s talk as part of the Annual Meeting’s Opening Reception. The new Advancing Medicine: Inspiration and Innovation talks are a series of three unique sessions that explore where neuroscience intersects with global themes. In addition to Herr’s talk, there will be a talk on the Flint water crisis at 1:00 p.m. on Monday, and a final talk on social morals at 1:00 p.m. on Wednesday. Be sure and make time in your schedule for these powerful and timely discussions and share what you found most inspiring at #AANAM.
Look for These Opportunities for ‘Continuing the Conversation’ All Week Long In response to last year’s successful pilot “Continuing the Conversation” programs, 2019 Annual Meeting attendees can expect to find even more opportunities to connect one-on-one with faculty, directors, and other attendees via 30-minute, small-group conversations at the conclusion of select courses. Look for the following sessions throughout the week: C34: Evaluating Tremor in the Office
Saturday, May 4 / 3:30 p.m.–4:00 p.m.
C76: Assessment of Rapidly Progressive Dementias II:
Infections and Autoimmune Mediated Conditions Sunday, May 5 / 5:30 p.m.–6:00 p.m.
C120: Clinical EMG II: Case-based Clinical Applications of
Nerve Conduction Studies and Needle Electromyography Monday, May 6 / 5:30 p.m.–6:00 p.m.
C164: Update on Medical Management of Stroke
Tuesday, May 7 / 5:30 p.m.–6:00 p.m.
C203: Comprehensive Migraine Update II: Pharmacologic
and Non-pharmacologic Therapies
C204: Neuro-ophthalmology III: Diplopia, Ocular
Motility Disorders, and Nystagmus Wednesday, May 8 / 5:30 p.m.–6:00 p.m.
C236: Neuro-rheumatology: Neurological Manifestations
of Systemic Inflammatory and Autoimmune Disease II Thursday, May 9 / 5:30 p.m.–6:00 p.m.
In addition, be sure to look for the new “Continuing the Conversation: Coding” program, which will offer similar post-course opportunities to talk one-on-one with a coding expert: Herr
C68: Cerebrovascular Disease IV: Telestroke
Sunday, May 5 / 5:30 p.m.–6:00 p.m.
C155: Deep Brain Stimulation II: Advanced Management
in Movement Disorders and Applications Beyond Movement Disorders Tuesday, May 7 / 5:30 p.m.–6:00 p.m.
NEW IN
2019
CONTINUING THE CONVERSATION SATURDAY • SUNDAY MONDAY • TUESDAY WEDNESDAY • THURSDAY
Saturday, May 4, 2019 • AANextra
33
THE FIRST FDA-APPROVED TREATMENT INDICATED FOR ADULTS WITH TARDIVE DYSKINESIA (TD)1
ONE CAPSULE, ONCE DAILY1 Convenient, once-daily dosing without complex titration1
Not actual size
• INGREZZA 80 mg provided rapid and significant reductions in TD severity by 6 weeks1,2 —with continued reductions in TD severity through 48 weeks1,3 • Generally well tolerated in clinical trials across a broad range of adult TD patients1,2 • Selectively inhibits VMAT2, with no appreciable binding affinity for serotonergic or dopaminergic receptors1 • Offers convenient, once-daily dosing without complex titration1 VMAT2, vesicular monoamine transporter 2.
Not an actual patient
I S I T T D O R A C U T E E P S ? | TA K E T H E T D C H A L L E N G E AT B O OT H # 9 0 0 EPS, extrapyramidal symptoms.
W W W. I N G R E Z Z A H C P. C O M
Important Information INDICATION & USAGE
INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.
IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.
WARNINGS & PRECAUTIONS Somnolence
INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.
QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
ADVERSE REACTIONS
The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see the adjacent page for brief summary of Prescribing Information and visit www.INGREZZAHCP.com/PI for full Prescribing Information. REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2018. 2. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484. 3. Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: results of the 1-Year KINECT 3 extension study. J Clin Psychiatry. 2017;78(9):1344-1350.
©2019 Neurocrine Biosciences, Inc. All Rights Reserved. CP-VBZ-US-0525v2 5/19
for oral use
Brief Summary: for full Prescribing Information and Patient Information, refer to package insert. INDICATIONS AND USAGE
Endocrine Disorders: blood glucose increased General Disorders: weight increased Infectious Disorders: respiratory infections Neurologic Disorders: drooling, dyskinesia, extrapyramidal symptoms (non-akathisia) Psychiatric Disorders: anxiety, insomnia During controlled trials, there was a dose-related increase in prolactin. Additionally, there was a dose-related increase in alkaline phosphatase and bilirubin, suggesting a potential risk for cholestasis.
Postmarketing Experience
INGREZZA® is indicated for the treatment of adults with tardive dyskinesia.
CONTRAINDICATIONS
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.
WARNINGS AND PRECAUTIONS Somnolence
INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.
QT Prolongation INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA concentrations may be higher and QT prolongation clinically significant. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. For patients taking a strong CYP3A4 inhibitor, reduce the dose of INGREZZA to 40 mg once daily. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
The following adverse reactions have been identified during post-approval use of INGREZZA that are not included in other sections of labeling. 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. Immune System Disorders: hypersensitivity reactions (including allergic dermatitis, angioedema, pruritis, and urticaria) Skin and Subcutaneous Tissue Disorders: rash
DRUG INTERACTIONS
Drugs Having Clinically Important Interactions with INGREZZA Table 2: Clinically Significant Drug Interactions with INGREZZA Monoamine Oxidase Inhibitors (MAOIs) Clinical Implication: Concomitant use of INGREZZA with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions such as serotonin syndrome, or attenuated treatment effect of INGREZZA. Prevention or Avoid concomitant use of INGREZZA with MAOIs. Management:
ADVERSE REACTIONS
Examples: isocarboxazid, phenelzine, selegiline Strong CYP3A4 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of INGREZZA alone. Increased exposure of valbenazine and its active metabolite may increase the risk of exposure-related adverse reactions. Prevention or Reduce INGREZZA dose when INGREZZA is coadministered with a strong CYP3A4 inhibitor. Management:
The following adverse reactions are discussed in more detail in other sections of the labeling: • Hypersensitivity • Somnolence • QT Prolongation
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. Variable and Fixed Dose Placebo-Controlled Trial Experience The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), including 445 patients. Patients were 26 to 84 years of age with moderate to severe tardive dyskinesia and had concurrent diagnoses of mood disorder (27%) or schizophrenia/ schizoaffective disorder (72%). The mean age was 56 years. Patients were 57% Caucasian, 39% African-American, and 4% other. With respect to ethnicity, 28% were Hispanic or Latino. All subjects continued previous stable regimens of antipsychotics; 85% and 27% of subjects, respectively, were taking atypical and typical antipsychotic medications at study entry. Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of INGREZZA treated patients and 2% of placebo-treated patients discontinued because of adverse reactions. Common Adverse Reactions Adverse reactions that occurred in the 3 placebo-controlled studies at an incidence of ≥2% and greater than placebo are presented in Table 1.
Table 1:
Adverse Reactions in 3 Placebo-Controlled Studies of 6-week Treatment Duration Reported at ≥2% and >Placebo
Adverse Reaction1
Examples: Strong CYP3A4 Inducers Clinical Implication:
paroxetine, fluoxetine, quinidine
Prevention or Management:
Concomitant use of strong CYP3A4 inducers with INGREZZA is not recommended. rifampin, carbamazepine, phenytoin, St. John’s wort1
Digoxin concentrations should be monitored when co-administering INGREZZA with digoxin. Increased digoxin exposure may increase the risk of exposure related adverse reactions. Dosage adjustment of digoxin may be necessary.
INGREZZA (n=262) (%)
Placebo (n=183) (%)
General Disorders Somnolence (somnolence, fatigue, sedation)
10.9%
4.2%
Examples: Digoxin Clinical Implication:
Nervous System Disorders Anticholinergic effects (dry mouth, constipation, disturbance in attention, vision blurred, urinary retention)
5.4%
4.9%
Prevention or Management:
Balance disorders/fall (fall, gait disturbance, dizziness, balance disorder)
4.1%
2.2%
Headache Akathisia (akathisia, restlessness)
3.4% 2.7%
Gastrointestinal Disorders Vomiting Nausea Musculoskeletal Disorders Arthralgia 1
Examples: itraconazole, ketoconazole, clarithromycin Strong CYP2D6 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP2D6 inhibitors may increase the exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of INGREZZA alone. Increased exposure of active metabolite may increase the risk of exposurerelated adverse reactions. Prevention or Consider reducing INGREZZA dose based on tolerability when INGREZZA is coadministered with a strong CYP2D6 inhibitor. Management:
2.7% 0.5%
1
Concomitant use of INGREZZA with a strong CYP3A4 inducer decreased the exposure of valbenazine and its active metabolite compared to the use of INGREZZA alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.
Concomitant use of INGREZZA with digoxin increased digoxin levels because of inhibition of intestinal P-glycoprotein (P-gp).
The induction potency of St. John’s wort may vary widely based on preparation.
Drugs Having No Clinically Important Interactions with INGREZZA Dosage adjustment for INGREZZA is not necessary when used in combination with substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5 based on in vitro study results.
OVERDOSAGE
Human Experience 2.6% 2.3%
0.6% 2.1%
2.3%
0.5%
Within each adverse reaction category, the observed adverse reactions are listed in order of decreasing frequency.
Other Adverse Reactions Observed During the Premarketing Evaluation of INGREZZA
Other adverse reactions of ≥1% incidence and greater than placebo are shown below. The following list does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo.
The pre-marketing clinical trials involving INGREZZA in approximately 850 subjects do not provide information regarding symptoms with overdose.
Management of Overdosage No specific antidotes for INGREZZA are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. If an overdose occurs, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org). For further information on INGREZZA, call 84-INGREZZA (844-647-3992). Distributed by: Neurocrine Biosciences, Inc. San Diego, CA 92130 INGREZZA is a registered trademark of Neurocrine Biosciences, Inc. CP-VBZ-US-0203v3 08/18
Axon Registry Experts on Hand to Answer Your Questions in Philly
See What the Synapse Buzz Is About at Experience the AAN Area
continuing certification (formerly known as MOC) requirements for the American Board of Psychiatry and Neurology (ABPN).
SynapseSM Online Communities, the official communication platform for AAN Sections, continues to experience substantial growth and engagement. You can find out what all the buzz is about by stopping by the Experience the AAN: Make the Most of Your Membership Experiential Learning Area throughout the week.
Continued from cover
Physician experts will be on hand for the entire meeting. Additionally, a representative from registry vendor Jones FIGmd will be available through May 8 to answer technical questions and share information about the process. Stop by to see demonstrations of the dashboard and discover how having registry data at your fingertips can be a valuable resource for your practice. “Now is the time to decide how you will fulfill Quality Payment Program requirements,” said Lyell K. Jones, Jr., MD, FAAN, chair of the Registry Committee. “The Axon Registry will help neurologists satisfy three out of four MIPS components. Also, the Axon Registry participation is approved by the ABPN as an continuing certification Part IV PIP Clinical Module activity and can be used to waive eight credits of Part II self-assessment.” If you’re looking for how Axon Registry participation will help your practice save time and be more efficient in handling reporting requirements and implement quality improvement initiatives, stop by the booth and get all your questions answered. Don’t miss this opportunity to learn how to successfully track the quality of care in your practice.
As an exclusive benefit of AAN membership, Synapse
now includes 40 open communities, comprised of sections and member-interest communities, as well as 16 private communities, all to serve more than 19,000 member neurologists and neuroscience professionals, residents and fellows, researchers, advanced practice providers, and businesses administrators from around the world who use the platform to exchange insights on professional-related topics and issues
Share expertise, find answers to tough questions, and
strengthen the care they provide
Discuss timely news and science affecting the field of
neurology
Offer real-world solutions to practice, patient care,
academia, and other areas of the neurology profession— across all career levels
Quickly and easily provide feedback on section-relevant
AAN programs and services
Download and share documents and images through the
Synapse digital library
Visit AAN.com/Synapse to join and get connected.
Saturday, May 4, 2019 • AANextra
37
What Are Your Colleagues Saying? Share your thoughts at #AANAM. Join the conversation!
#AANAM Diana M. Barratt, MD, MPH, FAAN Miami, FL Clerkship Director Teaching Award recipient, incoming chair of the Ethics Section, platform and poster session presenter “What advice do you have for first-time attendees?” “There are lots of sessions for trainees. Try to get involved in as many as you can. The meeting is a great way to network with people who may give you a job later—in a less formal setting.”
Hal Tobias, MD, FAAN Palm City, FL “Why are you attending the Annual Meeting?” “Just the education, the great courses and getting the newest information. That’s what your patients expect and that’s what they’re paying you for. I’m attending all of the Neurology Update courses—you get a little of everything with the updates—and a little extra on stroke. I’ve been doing traumatic brain injury evaluations for the VA, going all around the country.”
Babawale Arabambi, MBBS, FWACP Ikeja, Nigeria International Scholarship Award recipient “What are you looking forward to at this Annual Meeting?” “Everything. This is my first time to attend. I had a chance to go through the app before I got here, and there’s everything here. It took me a while to go through and decide what to go to. Apart from all of the regular courses, I was excited to see that there are lots of games, like Neuro Jeopardy.”
Fatima Abrantes-Pais, MD Oklahoma City, OK “Why do you come to the Annual Meeting?” “Networking. Updating. Fun. I always enjoy intellectual stimulation. All the new things giving you ideas, thoughts on how to spruce things up on my service, and networking and getting ideas from other people. The most fun I had at an Annual Meeting was last year in Los Angeles—my daughter received an AAN scholarship to attend as a second-year medical student. We shared a room and I got to attend with her!”
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©2019 Greenwich Biosciences Inc. All rights reserved. EPX-04965-0319
Latest Translational Research Unveiled in Today’s Hot Topics Plenary Continued from cover
Speakers and topics include:
Immunotherapies in Movement Disorders Virginia Lee, PhD University of Pennsylvania, Philadelphia, PA
SATURDAY, MAY 4 11:30 A.M.–1:00 P.M.
Solving Neurological Mysteries with Lesion Network Mapping
Locations: Exhibit Hall E (limited quantities available at Broad Street Atrium)
Michael D. Fox, MD, PhD Beth Israel Deaconess Medical School, Boston, MA
Evolution of AAVs for Widespread Gene Delivery to the Central Nervous System Sripriya Ravindra Kumar Gradinaru Lab, California Institute of Technology, Pasadena, CA
Patient-Customized Oligonucleotide Therapy for an Ultra-Rare Neurogenetic Disease Timothy W. Yu, MD, PhD Boston Children’s Hospital, Boston, MA
What is your aha moment from the Hot Topics Plenary Session? Join the conversation at #AANAM.
#AANAM 40
Saturday, May 4, 2019 • AANextra
Boxed Lunch Menu Lunch Options Option I:
Red Kale & Millet Salad/Lime Vinaigrette
Chilled Chimichurri Chicken
Cilantro Vinaigrette Potato Salad
Citrus Roasted Carrots
Flourless Chocolate Cake
Option II Vegan/Vegetarian/ Gluten Free:
Red Kale & Millet Salad/Lime Vinaigrette
Chilled Chimichurri Portobello Mushroom
Cilantro Vinaigrette Potato Salad
Citrus Roasted Carrots
Flourless Chocolate Cake
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INDICATION Oxtellar XR® is indicated for the treatment of partial-onset seizures in patients 6 years of age and older. CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, or to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. *Terms and conditions apply. Not actual patient. Fictionalized for illustrative purposes. References: 1. Oxtellar XR [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc.; December 2018. 2. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21(8):904-919. 3. French JA, Baroldi P, Brittain ST, Johnson JK; for PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014;129:143-153.
Please refer to the brief summary of full Prescribing Information on adjacent pages, or visit www.OxtellarXR.com. Oxtellar XR is a registered trademark of Supernus Pharmaceuticals, Inc. ©2019 Supernus Pharmaceuticals, Inc. All rights reserved. SPN.OXT.2019-0023
Powerfully evident choice
OXTELLAR XR® (oxcarbazepine) extended-release tablets, for oral use Brief Summary of Prescribing Information For full prescribing information, see Package Insert. CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. WARNINGS AND PRECAUTIONS Hyponatremia Clinically significant hyponatremia (sodium <125 mmol/L) may develop during Oxtellar XR® use. Serum sodium levels less than 125 mmol/L have occurred in immediate-release oxcarbazepine-treated patients generally in the first three months of treatment. However, clinically significant hyponatremia may develop more than a year after initiating therapy. Most immediate-release oxcarbazepine-treated patients who developed hyponatremia were asymptomatic in clinical trials. However, some of these patients had their dosage reduced, discontinued, or had their fluid intake restricted for hyponatremia. Serum sodium levels returned toward normal when the dosage was reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction). Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during post-marketing use of immediate-release oxcarbazepine. Among treated patients in a controlled trial of adjunctive therapy with Oxtellar XR® in 366 adults with complex partial seizures, 1 patient receiving 2400 mg experienced a severe reduction in serum sodium (117 mEq/L), requiring discontinuation from treatment, while 2 other patients receiving 1200 mg experienced serum sodium concentrations low enough (125 and 126 mEq/L) to require discontinuation from treatment. The overall incidence of clinically significant hyponatremia in patients treated with Oxtellar XR® was 1.2%, although slight shifts in serum sodium concentrations from Normal to Low (<135 mEq/L) were observed for the 2400 mg (6.5%) and 1200 mg (9.8%) groups compared to placebo (1.7%). Measure serum sodium concentrations if patients develop symptoms of hyponatremia (e.g., nausea, malaise, headache, lethargy, confusion, obtunded consciousness, or increase in seizure frequency or severity). Consider measurement of serum sodium concentrations during treatment with Oxtellar XR®, particularly if the patient receives concomitant medications known to decrease serum sodium levels (for example, drugs associated with inappropriate ADH secretion). Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of immediate-release oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with Oxtellar XR®, discontinue the drug and initiate an alternative treatment. Do not rechallenge these patients with Oxtellar XR®. Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with Oxtellar XR®. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with Oxtellar XR® only if the potential benefit justifies the potential risk. Discontinue Oxtellar XR® immediately if signs or symptoms of hypersensitivity develop. Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in both children and adults treated with immediate-release oxcarbazepine use. The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following rechallenge with immediate-release oxcarbazepine has also been reported. The reporting rate of TEN and SJS associated with immediaterelease oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking Oxtellar XR®, consider discontinuing Oxtellar XR® use and prescribing another AED. Association with HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with Oxtellar XR® treatment. Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structures of immediate-release oxcarbazepine and Oxtellar XR® are similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between immediate-release oxcarbazepine and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with Oxtellar XR®. The frequency of HLA-B*1502 allele ranges from 2 to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively. The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (<1%). Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with Oxtellar XR®. The use of Oxtellar XR® should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLA-B*1502 is low, or in current Oxtellar XR® users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status. The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dosage, compliance, concomitant medications, comorbidities, and the level of
dermatologic monitoring have not been well characterized. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including Oxtellar XR®, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Epilepsy: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 3.4. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 3.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4. Psychiatric: Placebo Patients with Events per 1000 Patients 5.7. Drug Patients with Events per 1000 patients 8.5. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.9. Other: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 1.8. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.9. Risk Difference: Additional Drug Patients with Events per 1000 Patients 0.9. Total: Placebo Patients with Events per 1000 Patients 2.4. Drug Patients with Events per 1000 patients 4.3. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.8. Risk Difference: Additional Drug Patients with Events per 1000 Patients 1.9. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing Oxtellar XR® or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during Oxtellar XR® treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Withdrawal of AEDs As with most AEDs, Oxtellar XR® should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with immediate-release oxcarbazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocaraditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. Oxtellar XR® should be discontinued if an alternative etiology for the signs and symptoms cannot be established. Hematologic Reactions Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with immediate-release oxcarbazepine during post-marketing experience. Discontinuation of Oxtellar XR® should be considered if any evidence of these hematologic reactions develops. Risk of Seizures in the Pregnant Patient Due to physiological changes during pregnancy, plasma concentrations of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may gradually decrease throughout pregnancy. Monitor patients carefully during pregnancy and through the postpartum period because MHD concentrations may increase after delivery. Risk of Seizure Aggravation Exacerbation of or new onset primary generalized seizures has been reported with immediate-release oxcarbazepine. The risk of aggravation of primary generalized seizures is seen especially in children but may also occur in adults. In case of seizure aggravation, Oxtellar XR® should be discontinued. ADVERSE REACTIONS 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 clinical practice. The safety data presented below are from 384 patients with partial-onset seizures who received Oxtellar XR® (366 adults and 18 pediatric patients) with concomitant AEDs. In addition, safety data presented below are from a total of 2288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1832 were adults and 456 were pediatric patients.
Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxtellar XR® Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with Oxtellar XR® or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of Oxtellar XR® than in patients receiving placebo. The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period. The most commonly observed (≥5%) adverse reactions seen in association with Oxtellar XR® and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia. Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxtellar XR® with Concomitant AEDs in Adults* Oxtellar XR® 2400 mg/day (N=123); Oxtellar XR® 1200 mg/day (N=122). Placebo (N=121). Any System/Any Term: 69%, 57%, 55%. Nervous System Disorders: Dizziness: 41%, 20%, 15%; Somnolence: 14%, 12% 9%; Headache: 15% 8%, 7%; Balance Disorder: 7%, 5% 5%; Tremor: 1%, 5%, 2%; Nystagmus: 3%, 3%, 1%; Ataxia 1%, 3%, 1%. Gastrointestinal Disorders: Vomiting: 15% 6%, 9%; Abdominal Pain Upper: 0%, 3% 1%; Dyspepsia: 0% 3% 1%; Gastritis: 0%, 3% 2%. Eye Disorders: Diplopia: 13%, 10% 4%; Vision Blurred: 1%, 4%, 3%; Visual Impairment: 1%, 3%, 0%. General Disorders and Administration Site Conditions: Asthenia: 7% 3%, 1%; Fatigue: 3%, 6%, 1%; Gait Disturbance: 0%, 3%, 1%; Drug Intolerance: 2%, 0%, 0%. Infections and Infestations: Nasopharyngitis: 0% 3%, 0%; Sinusitis: 0%, 3%, 2%. *Reported by ≥2% of patients treated with Oxtellar XR® and numerically more frequent than in the placebo group. Adverse Reactions Associated with Discontinuation of Oxtellar XR® Treatment: Approximately 23.3% of the 366 adult patients receiving Oxtellar XR® in clinical studies discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation of Oxtellar XR® (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%). Adjunctive Therapy with Oxtellar XR® in Pediatric Patients 6 to Less Than 17 Years of Age Previously Treated with Other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of Oxtellar XR®, the observed adverse reactions seen in association with Oxtellar XR® were similar to those seen in adults. Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with Other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo. As immediate-release oxcarbazepine and Oxtellar XR® were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations. Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day): OXC 600 (N=163); OXC1200 (N=171); OXC2400 (N=126); Placebo (N=166). Body as a Whole: Fatigue: 15%, 12%, 15%, 7%; Asthenia: 6% 3%, 6%, 5%; Edema Legs: 2%, 1%, 2%, 1%; Weight Increase: 1%, 2%, 2%, 1%; Feeling Abnormal: 0%, 1%, 2%, 0%. Cardiovascular System: Hypotension: 0%, 1%, 2%, 0%. Digestive System: Nausea: 15%, 25%, 29% 10%; Vomiting: 13%, 25%, 36%, 5%; Pain Abdominal: 10%, 13%, 11%, 5%; Diarrhea: 5%, 6%, 7%, 6%; Dyspepsia: 5%, 5%, 6%, 2%; Constipation: 2%, 2%, 6%, 4%; Gastritis: 2%, 1%,2%,1%. Metabolic and Nutritional Disorders: Hyponatremia: 3%, 1%, 2%,1%. Musculoskeletal System: Muscle Weakness: 1%, 2%, 2%, 0%; Sprains and Strains: 0%, 2%, 2%, 1%. Nervous System: Headache: 32%, 28% 26%, 23%; Dizziness: 36%, 32%, 49%, 13%; Somnolence: 20%, 28%, 36%, 12%; Ataxia: 9%, 17%, 31%, 5%; Nystagmus: 7% 20%, 26% 5%; Gait Abnormal: 5%, 10%, 17%, 1%; Insomnia: 4%, 2%, 3%, 1%; Tremor: 3% 8%, 16%, 5%; Nervousness: 2%, 4%, 2%, 1%; Agitation: 1%,1%, 2%, 1%; Coordination Abnormal: 1%, 3%, 2%, 1%; EEG Abnormal: 0%, 0%, 2%, 0%; Speech Disorder: 1%, 1%, 3%, 0%; Confusion: 1%, 1%, 2%, 1%; Cranial Injury NOS: 1%, 0%, 2% 1%; Dysmetria: 1%, 2%, 3%, 0%; Thinking Abnormal: 0%, 2%, 4%, 0%. Respiratory System: Rhinitis: 2%, 4%, 5%, 4%; Skin and Appendages: Acne: 1%, 2%, 2%, 0%; Special Senses: Diplopia: 14%, 30%, 40%, 5%; Vertigo: 6%, 12%, 15%, 2%; Vision Abnormal: 6%, 14%, 13%, 4%; Accommodation Abnormal: 0%, 0%, 2%, 0%. *Events in at least 2% of patients treated with 2400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group. Other Reactions Observed in Association with the Administration of Immediate-Release Oxcarbazepine In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to immediate-release oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor. They are listed in order of decreasing frequency. Because the reports cite reactions observed in open-label and uncontrolled trials, the role of immediate-release oxcarbazepine in their causation cannot be reliably determined. Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease. Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia. Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative. Hematologic and Lymphatic System: thrombocytopenia. Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased. Musculoskeletal System: hypertonia muscle. Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria,
extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany. Respiratory System: asthma, bronchitis, coughing, dyspnea, epistaxis, laryngismus, pleurisy. Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria. Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia. Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection. Other: Systemic lupus erythematosus. Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine. Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction). Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH. Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or Oxtellar XR®. 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. Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia, and arthralgia Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia Immune System Disorders: anaphylaxis Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH) Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Acute Generalized Exanthematous Pustulosis (AGEP) Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis and fractures in patients on long-term therapy with immediate-release oxcarbazepine. DRUG INTERACTIONS Effect of Oxtellar XR on Other Drugs It is recommended that the plasma levels of phenytoin be monitored during the period of Oxtellar XR titration and dosage modification. A decrease in the dosage of phenytoin may be required. Effect of Other Drugs on Oxtellar XR If Oxtellar XR and strong CYP3A4 inducers or UGT inducers (e.g., rifampin, carbamazepine, phenytoin, and phenobarbital) are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of Oxtellar XR titration. Dosage adjustment of Oxtellar XR may be required after initiation, dosage modification, or discontinuation of such inducers. Hormonal Contraceptives Concurrent use of immediate-release oxcarbazepine with hormonal contraceptives may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been conducted. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Oxtellar XR, during pregnancy. Encourage women who are taking Oxtellar XR during pregnancy to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate data on the developmental risks associated with the use of Oxtellar XR® in pregnant women; however, Oxtellar XR® is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD). 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. Clinical Considerations An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period. Data Human Data Data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure. Animal Data When pregnant rats were given oxcarbazepine (30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥300 mg/kg were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects. In a study in which pregnant rabbits were orally administered MHD (20,
100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m2 basis). This dose produced only minimal maternal toxicity. In a study in which female rats were dosed orally with oxcarbazepine (25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (0.6 times the MRHD on a mg/m2 basis). Oral administration of MHD (25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m2 basis). Lactation Risk Summary Oxcarbazepine and its active metabolite (MHD) are present in human milk after oxcarbazepine administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Oxtellar XR and any potential adverse effects on the breastfed infant from Oxtellar XR or from the underlying maternal condition. Females and Males of Reproductive Potential Contraception Use of Oxtellar XR with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. Advise women of reproductive potential taking Oxtellar XR who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control. Pediatric Use The safety and effectiveness of Oxtellar XR® in pediatric patients 6 years of age and older for the treatment of partial-onset seizures is supported by: 1) An adequate and well-controlled safety and efficacy study of Oxtellar XR® in adults that included pharmacokinetic sampling, 2) A pharmacokinetic study of Oxtellar XR® in pediatric patients, which included patients 6 to less than 17 years of age, 3) Safety and efficacy studies with the immediate-release formulation in adults and pediatric patients. Oxtellar XR® is not approved for pediatric patients less than 6 years of age because the size of the tablets are inappropriate for younger children. Geriatric Use Following administration of single (300 mg) and multiple (600 mg/day) doses of immediate-release oxcarbazepine to elderly volunteers (60-82 years of age), the maximum plasma concentrations and AUC values of MHD were 30%-60% higher than in younger volunteers (18-32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Consider starting at a lower dosage and lower titration. Close monitoring of sodium levels is required in elderly patients at risk for hyponatremia. Renal Impairment There is a linear correlation between creatinine clearance and the renal clearance of MHD. The pharmacokinetics of Oxtellar XR® has not been evaluated in patients with renal impairment. In patients with severe renal impairment (creatinine clearance <30 mL/min) given immediate-release oxcarbazepine, the elimination half-life of MHD was prolonged with a corresponding two-fold increase in AUC. In these patients initiate Oxtellar XR® at a lower starting dosage and increase, if necessary, at a slower than usual rate until the desired clinical response is achieved. In patients with end-stage renal disease on dialysis, it is recommended that immediate-release oxcarbazepine be used instead of Oxtellar XR®. Hepatic Impairment The pharmacokinetics of oxcarbazepine and MHD has not been evaluated in severe hepatic impairment, and therefore is not recommended in these patients. DRUG ABUSE AND DEPENDENCE Abuse The abuse potential of Oxtellar XR® has not been evaluated in human studies. Oxtellar XR® is not habit forming, and is not expected to encourage abuse. Dependence Intragastric injections of oxcarbazepine to four cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity. OVERDOSAGE Human Overdose Experience Isolated cases of overdose with immediate-release oxcarbazepine have been reported. The maximum dose taken was approximately 48,000 mg. All patients recovered with symptomatic treatment. Nausea, vomiting, somnolence, aggression, agitation, hypotension, and tremor each occurred in more than one patient. Coma, confusional state, convulsion, dyscoordination, depressed level of consciousness, diplopia, dizziness, dyskinesia, dyspnea, QT prolongation, headache, miosis, nystagmus, overdose, decreased urine output, and blurred vision also occurred. Treatment and Management There is no specific antidote for Oxtellar XR® overdose. Administer symptomatic and supportive treatment as appropriate. Options include removal of the drug by gastric lavage and/or inactivation by administering activated charcoal. CLINICAL PHARMACOLOGY Patients with Renal or Hepatic Impairment The effects of renal or hepatic impairment have not been studied for Oxtellar XR®. Based on investigations with immediate-release oxcarbazepine, there is a linear correlation between creatinine clearance and the renal clearance of MHD. When immediate-release oxcarbazepine is administered as a single 300 mg dose in renally-impaired patients (creatinine clearance <30 mL/min), the elimination half-life of MHD is prolonged to 19 hours, with a two-fold increase in AUC. Dosage adjustment is recommended in these patients. The pharmacokinetics and metabolism of immediate-release oxcarbazepine and MHD were evaluated in healthy volunteers and hepatically impaired subjects after a single 900 mg oral dose. Mild-to-moderate hepatic impairment did not affect the pharmacokinetics of immediate-release oxcarbazepine and MHD. The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment, and therefore it is not recommended in these patients. Pregnant Women Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy. Drug Interaction Studies
In Vitro: Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9, and CYP4A11) with the exception of CYP2C19 and CYP3A4/5. Although inhibition of CYP3A4/5 by oxcarbazepine and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP2C19 by oxcarbazepine and MHD, is clinically relevant. In vitro, the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine). In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives and cyclosporine resulting in a lower plasma concentration of these drugs. Several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. No autoinduction has been observed with immediate-release oxcarbazepine. As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely. In Vivo: Other Antiepileptic Drugs Potential interactions between immediate-release oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 5. Table 5: AED Drug Interactions with Immediate-Release (IR) Oxcarbazepine AED Coadministered (daily dosage); IR-Oxcarbazepine (daily dosage); Influence of IR-Oxcarbazepine on AED Concentration Mean Change (90% Confidence Interval); Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval). Carbamazepine (400-2000 mg): 900 mg, nc1, 40 % decrease [Cl: 17% decrease, 57% decrease]; Phenobarbital (100-150 mg): 600-1800 mg, 14% increase [Cl: 2% increase, 24% increase]; 25% decrease [Cl: 12% decrease, 51% decrease]. Phenytoin (250-500 mg): 600-1800 >1200-2400, nc1,2 up to 40% increase3 [Cl: 12% increase, 60% increase], 30% decrease [Cl: 3% decrease, 48% decrease]. Valproic Acid (400-2800 mg): 600-1800, nc1, 18% decrease [Cl: 13% decrease, 40% decrease]. Lamotrigine (200 mg): 1200, nc1, nc1. 1 nc denotes a mean change of less than 10%; 2Pediatrics; 3 Mean increase in adults at high doses of immediate-release oxcarbazepine Hormonal Contraceptives Coadministration of immediate-release oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of two components of hormonal contraceptives, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study. Other Drug Interactions Calcium Antagonists: After repeated coadministration of immediate-release oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20-33]. Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD after coadministration with immediate-release oxcarbazepine. Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD after coadministration with immediate-release oxcarbazepine. Results with warfarin show no evidence of interaction with either single or repeated doses of immediate-release oxcarbazepine. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In two-year carcinogenicity studies, oxcarbazepine was administered in the diet at doses of up to 100 mg/kg/day to mice and by gavage at doses of up to 250 mg/kg/day to rats, and the pharmacologically active 10-hydroxy metabolite (MHD) was administered orally at doses of up to 600 mg/kg/day to rats. In mice, a dose-related increase in the incidence of hepatocellular adenomas was observed at oxcarbazepine doses ≥70 mg/kg/day or approximately 0.1 times the maximum recommended human dose (MRHD) on a mg/m2 basis. In rats, the incidence of hepatocellular carcinomas was increased in females treated with oxcarbazepine at doses ≥25 mg/kg/day (0.1 times the MRHD on a mg/m2 basis), and incidences of hepatocellular adenomas and/or carcinomas were increased in males and females treated with MHD at doses of 600 mg/kg/day (2.4 times the MRHD on a mg/m2 basis) and ≥250 mg/kg/day (equivalent to the MRHD on a mg/m2 basis), respectively. There was an increase in the incidence of benign testicular interstitial cell tumors in rats at 250 mg oxcarbazepine/kg/day and at ≥250 mg MHD/kg/day, and an increase in the incidence of granular cell tumors in the cervix and vagina in rats at 600 mg MHD/kg/day. Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in one of five bacterial strains. Both oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. MHD was negative in the Ames test, and no mutagenic or clastogenic activity was found with either oxcarbazepine or MHD in V79 Chinese hamster cells in vitro. Oxcarbazepine and MHD were both negative for clastogenic or aneugenic effects (micronucleus formation) in an in vivo rat bone marrow assay. Impairment of Fertility In a fertility study in which rats were administered MHD (50, 150, or 450 mg/kg) orally prior to and during mating and early gestation, estrous cyclicity was disrupted and numbers of corpora lutea, implantations, and live embryos were reduced in females receiving the highest dose (approximately two times the MRHD on a mg/m2 basis). RA-OXT-BS-PV2
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DISCOVER EMERGING SCIENCE IN NEUROLOGY FROM GENENTECH Sunday, May 5th 12:15 pm and 3:15 pm
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Associate Professor of Neurology The University of Chicago Chicago, Illinois
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Professor of Neurology and Pediatrics Division of Pediatric Neurology Columbia University Medical Center New York, New York
Dr Mark Cascione, MD Tampa Neurology Associates South Tampa Multiple Sclerosis Center Tampa, Florida
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