VOLUME 31 · ISSUE 8 · AUGUST 2017
Y O U R M O N T H LY A A N M E M B E R S H I P M A G A Z I N E
2018 AAN Award Applications Opening This Month Have you or someone you know been conducting research that may be advancing the field of neurology? If so, now is the time to start thinking about applying—or nominating a colleague— for one of over 20 AAN scientific awards to be presented at the 2018 AAN Annual Meeting in Los Angeles, CA, April 21 through 27. Online applications will be available later this month at AAN.com/view/18Awards, and the application deadline is October 25, 2017. Prestigious AAN awards honor the best research and achievements by neurologists and neuroscientists around the globe with prizes and other compensation, such as complimentary travel expenses and registration for the Annual Meeting. AAN awards recognize scientists at all stages of their careers for a variety of activities.
2018 AAN Annual Meeting Abstract Deadline: October 23 Watch for submission details in September!
Upcoming Webinar Helps You Engage with Your Patients Patient engagement is a factor in many online reviews of physicians. If you would like to improve your engagement with your patients and are looking for help to do so, register for this new practice management webinar from the AAN.
Open Your Heart, Open Your Notes: A Guide to Patient Engagement September 12, 2017 12:00 p.m.–1:00 p.m. ET Deadline to Register: September 11 Director: Allison L. Weathers, MD, FAAN Continued on page 8
September 8 Is Last Chance to Save $200 on Fall Conference Registration
THIS ISSUE 7
Participating in MIPS: Who Should and How to Do It
High-quality Service with Axon Registry
12 Don’t miss your chance to save as much as $200 off the on-site registration rate when you secure your spot for the 2017 AAN Fall Conference before the September 8 early registration and hotel reservation deadline. Continued on page 22
Report Examines Work-life Balance Issues for Residents and Fellows Task Force Recommends Book on Implicit Bias
SUPER-REFRACTORY STATUS EPILEPTICUS (SRSE) IS
A CRITICAL PUZZLE OF CLINICAL COMPLEXITY 1-3 SRSE is a life-threatening form of status epilepticus (SE) that continues or recurs for >24 hours despite multiple therapeutic interventions (first-, second-, and third-line agents).3,4
Ad Page THE BURDEN OF SRSE IS HIGH5 Approximately 65% to 70% of patients with refractory SE or SRSE will die or be left with neurological deficits1,6 Outcomes of refractory seizures worsen with longer duration of uncontrolled seizure activity,7 including risk of neuronal death,7-9 neuronal injury,7-9 and alteration of neuronal networks3,4 Limited evidence exists to guide treatment decisions for patients with SRSE after third-line treatment failure3,4,10
Visit SRSE.com to learn more. References: 1. Delaj L, Novy J, Ryvlin P, Marchi NA, Rossetti AO. Refractory and super-refractory status epilepticus in adults: a 9-year cohort study. Acta Neurol Scand. 2017;135(1):92-99. 2. As reviewed in Bayrlee A, Ganeshalingam N, Kurczewski L, Brophy GM. Treatment of super-refractory status epilepticus. Curr Neurol Neurosci Rep. 2015;15(10):66. 3. As reviewed in Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134(Pt 10):2802-2818. 4. As reviewed in Hocker S, Tatum WO, LaRoche S, Freeman WD. Refractory and super-refractory status epilepticus â€“ an update. Curr Neurol Neurosci Rep. 2014;14(6):452. 5. Beg JM, Anderson TD, Francis K, et al. Burden of illness for super-refractory status epilepticus patients. J Med Econ. 2017;20(1):45-53. 6. As reviewed in Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314-2328. 7. Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia. 1994;35(5):1104-1112. 8. As reviewed in Payne TA, Bleck TP. Status epilepticus. Crit Care Clin. 1997;13(1):17-38. 9. As reviewed in Meldrum B. Excitotoxicity and epileptic brain damage. Epilepsy Res. 1991;10(1):55-61. 10. Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61.
ÂŠ 2017 Sage Therapeutics, Inc.
Official Publication of the American Academy of Neurology
PUBLICATION The Vision of the AAN is to be indispensable to our members. The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction. Contact Information American Academy of Neurology 201 Chicago Avenue Minneapolis, MN 55415 Phone: (800) 879-1960 (toll free) (612) 928-6000 (international) Email:
Website: AAN.com For advertising rates, contact: Eileen R. Henry Wolters Kluwer Health | Medical Research Lippincott, Williams & Wilkins Phone:
Table of Contents
COVER 2018 AAN Award Applications Opening This Month Upcoming Webinar Helps You Engage with Your Patients September 8 Is Last Chance to Save $200 on Fall Conference Registration
4 AAN Fights for Research Funding, Provides Support to Researchers
MEET YOUR LEADER
6 Charlene E. Gamaldo, MD, FAAN, FAASM
Editor-in-Chief: John D. Hixson, MD
10 Capitol Hill Report
11 Bike Helmet Giveaway Protects
Thousands of Twin Cities Brains
12 Report Examines Work-life
Balance Issues for Residents and Fellows
12 Task Force Recommends Book on Implicit Bias
20 Sleep Neurology Is Focus of August Continuum
20 Accreditation Granted to 12 New Programs
21 Practice Track Eligibility Extended
7 Participating in MIPS: Who
for Headache Medicine and Neuroimaging Certifications
8 Demonstrating High-quality
AMERICAN BRAIN FOUNDATION
Should and How to Do It
Service with Axon Registry
9 Enjoy Fresh Perspectives in AAN Executive Director Catherine M. Rydell, CAE
Neurology Now, Neurology: Clinical Practice
9 Podcast Central
24 Donor Spotlight: Meet Isabella:
Young Donor Bakes Cookies for Concussions
CAREERS | 26 DATES AND DEADLINES | 27
Managing Editor: Angela Babb, CAE Editor: Tim Streeter Writers: Ryan Knoke and Sarah Parsons Designers: Siu Lee and Jim Hopwood Email: aannews@AAN.com AANnews is published monthly by the American Academy of Neurology for its 32,000 members worldwide. Access this magazine and other AAN publications online at AAN.com/go/elibrary. 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.
NEWS BRIEFS The NeuroSAE Child Neurology Edition is now available. The free course offers 8 Self-assessment CME credits and features 100 questions based on the ABPN content outline for the child neurology exam. The free NeuroLearn: Recurrent Ischemic Stroke Prevention (Second Edition) course can be accessed by members. The new course offers 2 CME credits and provides up-to-date ischemic stroke guidance information and its application in practice, as well as new study information that may impact future recurrent stroke prevention. The Academy’s Instagram @AANBrain account won the Silver Award in the Social Media–Instagram category for the Spring 2017 Digital Health Awards. This was the highest-level award given for this category and the highest the AAN has received from the Digital Health Awards. The AAN’s Education Committee and Science Committee recently held a joint meeting that focused on developing a strong AAN-sponsored academic support system to demonstrate that the AAN is indispensable to all levels of academic medicine. •
AANnews • August 2017
AAN Fights for Research Funding, Provides Support to Researchers Promoting neurology and neuroscience research and training is fundamental to the AAN mission and a key part of our 2017 goals. Our patients are depending on us to accelerate cures for neurological conditions and translate the breakthroughs in neuroscience research to the clinic. As we move closer to the October 1 application deadline for a host of AAN Research Program awards and scholarships provided by your Academy and its partners, I’d like to share some concerns and opportunities regarding neurologic research. We have fought hard to preserve and improve funding for the National Institutes of Health (NIH) and the BRAIN Initiative. NIH funding was among our key asks in the 2017 Neurology on the Hill and we continued to push our advocacy messages throughout the budget process. We worked across party lines for two years to ensure the inclusion of strong research funding in last year’s 21st Century Cures Act, which included an increase of $4.8 billion for NIH, a 6.1-percent increase for NIH. Besides increasing the overall NIH budget, NINDS funding increased by 5.3 percent to $1.78 billion and NIA to a little over $2 billion, with $400 million more in funding for Alzheimer’s disease and related dementias, which we know have a major toll on our patients and their families. We also were successful in getting a $110 million increase for the BRAIN Initiative in 2017. This represents a 73-percent increase to $260 million, which was the largest bump for any NIH program. But those successes are now in danger of being undone. You’ve likely heard that President Trump has proposed a draconian $5.9 billion cut to the 2018 budget for NIH, a 21-percent reduction from 2017 funding levels. The president’s budget threatens millions in funding for the BRAIN Initiative that was authorized by the 21st Century Cures Act. These cuts could be crippling. Many of us remember the havoc that researchers and their valuable work endured when Congress enacted the budget “sequester” several years ago and NIH funds were cut back. Moreover, our patients and their families are the ones most threatened by this potential downward spiral in NIH funding as their hopes for faster cures are obliterated.
AANnews • August 2017
We cannot and will not let this occur! Both Republicans and Democrats have voiced their opposition to the president’s proposed budget, and with the urging of AAN advocates, 64 representatives and 10 senators have signed letters of support for the BRAIN Initiative. Our Government Relations Committee and advocacy staff are hard at work to defend against this devastating cut. The AAN will continue to strongly Ralph L. Sacco, MD, MS, FAHA, FAAN oppose the research cuts in the Trump budget proposal and will include research in our requests during Neurology “off” the Hill visits during the August congressional recess. Fortunately, what is proposed by the president can be changed or ignored by Congress—where we have the strongest influence due to the AAN’s acceptance as THE experts when it comes to neurology. Our political action committee, BrainPAC, has enabled us to educate members of Congress and helped us elect lawmakers who are allies in our work. While some congressional leaders have voiced support for research funding and opposition to the president’s budget, we can’t take it for granted we will win this round. I strongly urge you to stay fully engaged, read the Capitol Hill Report, and watch your email inbox over the coming weeks for action alert emails from the AAN. We will need all of our members to help in countering this assault on research funding. If we ask you to contact your representative and senators to preserve federal funding for scientific research—and brain research in particular—I hope you will respond swiftly. Grassroots advocacy across interest groups throughout the country helped stymie the administration’s initial American Health Care Act last spring, and we need that same passion applied to any research funding cuts. In this uncertain time, you can be very proud of the leadership your Academy is providing regarding research funding, not only in Washington, DC, but directly within the neurology
community. We are expanding our own commitments to fund the best and brightest and increase the future translational workforce for neurology research. The AAN has again teamed with the American Brain Foundation and five new partners— the McKnight Brain Research Foundation, Society of Vascular and Interventional Neurology, International Headache Society, Muscle Study Group, and The Mary E. Groff Charitable Trust— to add new scholarship awards to the 2018 AAN Research Program. Working with these and other organizations, the AAN is making good on its commitment to help support young researchers who will grow to shape the future of neurology and neuroscience, just as many of you have in your careers. And the AAN has gone further by establishing two larger-scale career development awards that fulfill its pledge to support all types of research across all career levels and discovery stages. These three-year awards will support junior investigators interested in an academic career in neurology and provide support of $150,000 per year for a total of $450,000. For more information about the 2018 AAN Research Program and to apply for scholarships by October 1, please visit AAN.com/view/ResearchProgram. We are also delighted to celebrate the 25th anniversary of the American Brain Foundation that we have helped develop, support, and expand. Over that time, it has distributed more than $24 million in funding to 233 recipients. The overwhelming majority of these young researchers have gone on to secure NIH grants and academic positions, and I firmly believe the endorsement of the Academy and Foundation of their skills and potential was a valuable boost to their success. The new energized American Brain Foundation Board, with more public, high-profile members, is taking bold steps to bring researchers and donors together to defeat brain disease.
ARE YOU READY? The MACRA’s new QUALITY PAYMENT PROGRAM is now in effect. Learn about your payment and reporting options and what you need to do now to ensure your highest reimbursement in 2019.
Power your practice with AAN resources.
The Foundation recently launched a crowdfunding platform to raise up to $100,000 for individual researcher campaigns. This platform is available to the public, and we are eager to see how we can connect people who have a passionate desire for a cure with those who have a passionate desire to discover the cure. You can learn more—and donate or apply for inclusion as a researcher—at AmericanBrainFoundation.org. The AAN is working at all angles to expand research that is so vital to the future brain health of our population. We need to fight together to halt any cuts to NIH and, if anything, expand funding for neurological research. While the government is at odds as to how much support it should provide to medical research, the AAN and the American Brain Foundation are doing everything we can to ensure that we continue to accelerate our progress toward discoveries, treatments, and cures for neurological conditions. I urge our members to join us and make the future much brighter for our patients and families.
Ralph L. Sacco, MD, MS, FAHA, FAAN President, AAN email@example.com
AANnews • August 2017
Meet Your Leader
Charlene E. Gamaldo, MD, FAAN, FAASM Charlene E. Gamaldo, MD, FAAN, FAASM, is associate professor for neurology, psychiatry, nursing, anesthesia, and public health at Johns Hopkins University. She is also the neurology department’s vice chair of faculty development and medical director at the Johns Hopkins Center for Sleep. She is a recipient of the AAN’s 2015 Clerkship Director Innovation Award. How did you first get involved as a volunteer on committees/ subcommittees and what moved you to participate? I have been a member of the AAN since 2002. In 2012, I had the honor of being selected to develop a NeuroLearn module on “Sleep and the Practicing Neurologist,” which afforded me the opportunity to visit the headquarters in Minneapolis and interact with fellow medical educators along with the AAN staff and leadership. This was my first exposure to the interworkings of the Academy and I left filled with pride at being a member of an organization that is not only housed within a beautiful, state-of-the-art building, but more importantly a building filled with incredibly loyal staff and leadership devoted to serving the mission and the members. It was at that point that I expressed my interest in becoming more active in the Academy, and from that time on I have willingly served on several committees— the Undergraduate Education Subcommittee, Conrad N. Hilton Foundation Medical Student Pipeline Work Group project, Sleep Section executive committee, Minority Scholars Subcommittee, and as an AAN abstract reviewer, to name a few. Why did you wish to serve on the Board of Directors? I was enthusiastic about the opportunity to serve as a representative on the AAN Board of Directors and lend effort in addressing many of the challenges identified by the AAN which are currently confronting our members. In the face of a rapidly changing health care landscape, I know incredible effort, resources, and expertise are warranted to tackle the reality facing our field. That includes addressing burnout, improving diversity, and increasing member engagement. At the same time, we must work together to continue to
AANnews • August 2017
pursue excellence in clinical care, education, and research investigation. I was honored and humbled to be chosen to serve the board and to do my part in fulfilling the mission. What experiences and viewpoints do you bring to this role? I have been moved by the concerted efforts of the Academy to increase diversity within the organization and leadership. I hope to add my perspective as an academic medical educator, clinical program builder in the subspecialty of sleep, that epitomizes interprofessional and interdisciplinary collaboration. As a member of the inaugural AAN Transforming Leaders Program, I hope to apply the skills learned there to effectively communicate my perspective in hope that I can help the AAN with the ongoing efforts to serve the membership. From your experiences as an AAN leader, what is one of the more common misperceptions members may have about the Academy? From my academic colleagues, I have sometimes heard that the AAN’s efforts are primarily focused on the clinical and private practice neurologist—yet my private practice colleagues feel that the AAN primarily focuses on the needs of the academic community. As I have become involved in the Academy, I have become more enlightened on the multipronged efforts of the AAN to represent the diverse needs of our membership to include a strong commitment to building upon the platform of the scientific program at the meeting, providing opportunity for early career funding in this challenging climate, and lobbying for the muchneeded appropriations of governmental spending in neuroscience research. At the same time, I have become more aware of the Academy’s efforts to
provide support to the clinical and private practice neurologist who face ongoing pressure to adjust to the changes in the medical landscape by providing resources and infrastructural support like the Axon Registry ® and prioritizing political action advocacy to lobby for equitable reimbursement for neurological services. In your view, how does the AAN benefit the field of neurology most? The Academy benefits the field the most by staying true to its fundamental tenet, which is to be an indispensable resource to its membership. To that end, I see the AAN benefiting neurology most by constantly looking for optimal ways to solicit members’ needs, utilizing its resources to help represent those needs to our members’ stakeholders (i.e., patients, community, and policy makers), and then effectively communicating the AAN’s progress in meeting those needs back to our membership. How should members evaluate the success of the AAN and the Board of Directors in supporting their careers and in neurology in general? I think this can be assessed in very simple ways. First of all, as individual members, they should ask on a periodic basis whether the AAN’s efforts and achievements have served in some way to be a valuable and indispensable resource to their career development and sustainability. Periodically track membership and volunteer numbers. People are less likely to maintain membership (and pay dues) or volunteer for an organization that they do not feel has their best interests at hand. •
Participating in MIPS: Who Should and How to Do It The passage of MACRA led to the creation of a new payment structure, the Quality Payment Program (QPP), which created two pathways by which Medicare Part B payment will be based: the Merit-based Incentive Payment Systems (MIPS) and Alternative Payment Models (APMs). Most neurologists, particularly those in solo or small practices, will participate in MIPS.
Not all physicians are required to participate in MIPS in 2017. You will be considered participating in MIPS unless:
You may still consider reporting in 2017 even if you’re exempt from MIPS to help you prepare for future years. Given the low threshold for participation, the Pick Your Pace program provides an opportunity for you to test MIPS reporting capabilities before 2018 when payment adjustments become more significant. If it’s possible you’d be required to participate in MIPS in 2018 (for example, if you’ll no longer be new to Medicare), take this opportunity to practice reporting and work through problems.
nn You participate in an APM and your participation is
sufficient to meet CMS thresholds. nn You are new to Medicare. If 2017 is your first year as
a Medicare participating provider, then you are exempt from participation. nn You meet the low-volume threshold. You would
meet this requirement if you see fewer than 100 Medicare beneficiaries or receive less than $30,000 in Part B fee-for-service payments. Visit https://qpp.cms.gov to enter your NPI and confirm whether you are exempt from participation.
Individual vs. Group Reporting You may be exempt as an individual, but you will still be required to participate in MIPS if your group (TIN) exceeds the low-volume threshold and decides to participate as a group. In other words, if some individuals in a group are exempt and some are not, and the group chooses to report as a group, everyone must participate in MIPS. MIPS assessment will be based on all individuals in the group, and any payment adjustment will still impact clinicians who do not exceed the low-volume threshold as individuals.
Pick Your Pace Clinicians can “pick the pace” of their participation, and the threshold to participate is fairly low for the first performance year. There are three participation options under the Pick Your Pace program: nn Test: Submit one quality measure, one improvement
activity, or the four required advancing care information (ACI) measures to avoid a penalty up to four percent. nn Partial Participation: Submit at least 90 days of data
for more than one quality measure or improvement activity OR more than the four required ACI measures to earn a neutral or small bonus. nn Full-year Participation: Submit at least 90 days of
data for all required quality measures and improvement activities, and more than the four required ACI measures to earn a moderate bonus.
Additionally, it will be relatively easy for many neurologists to participate in MIPS and, for some, to even collect bonuses. You likely already have experience reporting quality measures to CMS via PQRS and/or ACI measures through participation in the Medicare EHR Incentive Program. You can maximize your quality score by reporting via a quality clinical data registry like the AAN’s Axon Registry ®. Visit AAN.com/practice/mips for more information about how MIPS impacts your practice or contact firstname.lastname@example.org for answers to your questions. •
Problems with Your NPI? If you find that the information associated with your NPI is outdated or incorrect, the AAN recommends that you: 1. Verify your information through PECOS. Some data sent from PECOS to the CMS database could be incorrect. In this case, make sure the correct information has been entered into PECOS. 2. Contact QPP staff at email@example.com or (866) 288-8292 (Monday through Friday, 8:00 a.m. to 8:00 p.m.) if, after updating your information on PECOS, you still see incorrect information on the CMS database. 3. Take a screenshot of the information presented to keep for your records. •
AANnews • August 2017
Demonstrating High-quality Service with Axon Registry The Axon Registry®, a qualified clinical data registry (QCDR), has been a valuable resource for practices to initiate quality improvement, prove value to payers, and meet government reporting requirements. Since the completion of the pilot phases in January 2017, the registry has enrolled more than 140 practices with about 1,000 providers. Practices that were early adopters of the registry have found it to be a valuable resource for their practice.
our care among a wide range of subspecialist physicians, APPs, and levels of experience. We are finding that reducing variance in how we manage our patients, strategically focusing on scores falling below expectations, and tracking meaningful outcomes drives each provider to practice at a higher standard of care.”
Fritz’s practice submits government requirements through a different method than via the registry but he says they recognize the opportunity Dent Neurologic Institute in Buffalo, NY, joined the this provides them for the future. “Often our Joseph V. Fritz, PhD registry in 2015. The practice has 64 providers and physicians are judged on measures that have little uses the pull data extraction method from their relevance to their everyday practices. As a QCDR server-based eClinicalWorks EHR system. Dent with neurology-specific quality measures, the uses many of the measures in the registry, including those Axon Registry is a huge advantage for neurologists looking to meet requirements with minimal burden on their practice.” related to dementia, headache, epilepsy, diabetic sensorimotor polyneuropathy, Parkinson’s, and multiple sclerosis. Dent Neurologic Institute is just one example demonstrating how the Axon Registry can have a positive impact on a Joseph V. Fritz, PhD, is the chief executive officer and practice’s patient care. It has minimal burden on the provider’s technology director at Dent Neurologic Institute, and the practice and it calculates comprehensive performance rates current vice chair of the Registry Committee. Fritz has found from notes and discrete fields. Providers can view a userthe registry to be beneficial for his practice to demonstrate the friendly dashboard to see their performances and compare it value of their care and to continually implement improvement. to providers nationally. “The registry is, frankly, more than Other early adopters also have shared their experiences an opportunity to merely with the Axon Registry and more information is available in demonstrate that we the case study document found with other related articles offer a high-quality at AAN.com/view/Axon. Enrollment information is also on service,” he said. this site. As practices sign up, they will be placed on a wait “It is truly helping list and contacted when their number is reached. For more us improve our information or questions about enrolling your practice, contact quality by driving firstname.lastname@example.org. • a consistency in
Upcoming Webinar Helps You Engage with Your Patients
Continued from cover
Upon completion, you should be able to: nn Familiarize yourself with current patient engagement technology nn Employ tactics to enhance patient engagement nn Explore the OpenNotes concept of sharing medical information AAN practice management webinars provide the valuable insights and tools you need to navigate through the ever-changing health care landscape. Single webinars are $99 but AAN members get the greatest value with the $189 subscription to all 10 live one-hour webinars. All webinars include access to presentation slides and recordings if you miss the live event. Physicians receive 1 AMA PRA Category 1 Credit ™ per webinar; non-physicians receive a certificate of completion. Visit AAN.com/view/pmw17 to learn more and register. • Allison L. Weathers, MD, FAAN
AANnews • August 2017
Enjoy Fresh Perspectives in Neurology Now, Neurology: Clinical Practice The cover story of the August/September 2017 issue of Neurology Now ® features actor Chris Jackson, star of Broadway’s Hamilton and television’s Bull, and his wife Veronica-Vazquez Jackson, who share the story of their son CJ, who was diagnosed with autism 10 years ago.
Short profiles of working artists who have neurologic conditions are featured in “How My Brain Affects My Art,” including artist Paula Hayes, who has epilepsy; jazz musician John McNeil, who has Charcot-Marie-Tooth disease; sculptor Rebecca Kaman, who has dyslexia; and Emmy Award-winning filmmaker Jason DaSilva, who has primary progressive MS. AAN members may elect to receive multiple copies of Neurology Now to distribute to their patients, who also can subscribe for free. Visit NeurologyNow.com to learn more or access your AAN member profile to adjust the number of copies you receive.
Volume 7, Number 4
YOUR TRUSTED RESOURCE FOR BRAIN HEALTH
AUGUST / SEPTEMBER 2017
“OUR SON ” HAS AUTISM Practice Current:
Bull’s Christopher Jackson and How DoWife You TreatVasquez-Jackson Epilepsy in Pregnancy? Veronica Rise to the Challenge
Review: Wearable biosensors My Illness, My Art to monitor disability in MS Four Artists Describe How Brain Disease Shapes Their Art
Research: Perspectives on marijuana use and effectiveness
In the latest issue of Neurology ® Clinical Practice, concerns about anticoagulants and mild brain injury is the subject of an article and editorial. Other articles review online tools for individuals with depression and neurological conditions and examine a survey of NARCOMS participants for perspectives on marijuana use and effectiveness.
Research: Mild brain injury and anticoagulants
How to Lessen the Cost of Medical Care Myasthenia Gravis Diagnosis, Treatment, Research
Neurology: Clinical Practice, published six times a year, is available in print (for US members only), online, and for the iPad and Android. Visit Neurology.org/cp for more information. •
13 mi lli Ov an on d er d g ow row nlo ing ads ... !
Your Guide to New and Recent AAN Podcasts
Neurology ® Podcasts Visit Neurology.org to listen to Neurology podcasts and earn 0.5 AMA PRA Category 1 CME Credits™ by answering the multiple-choice questions in the online podcast quiz. Interviews based on articles from Neurology ® Clinical Practice, Neurology ® Genetics, and Neurology ® Neuroimmunology & Neuroinflammation are excluded from the CME program.
Available by August 1 nn Neurology: On Being Sick: Musings About Kindness, Side Effects, and Slowing Down Ted M. Burns, MD, and Alberto J. Espay, MD, MSc nn Neurology: Quality Improvement in Neurology: Inpatient and Emergency Care Quality Measure Set Executive Summary Jason Crowell, MD, and Paul Marino Vespa, MD nn Neurology: Oral Fluoroquinolones and Risk of Secondary Pseudotumor Cerebri Syndrome Beau Benjamin Bruce, MD, PhD, and Mahyar Michael Etminan, PharmD, MSc (Epi) nn Neurology: Prognostic Relevance of MOG Antibodies in Children with an Acquired Demyelinating Syndrome? J. Nicholas Brenton, MD, and Kevin Rostásy, MD, PhD nn Neurology: Clinical Practice: Barriers and Facilitators to ER Physician Use of the Test and Treatment for BPPV James E. Siegler, MD; Kevin Anthony Kerber, MD; and William J. Meurer, MD, MS
AANnews • August 2017
Capitol Hill Report Capitol Hill Report presents regular updates on legislative and regulatory actions and how the Academy ensures that the voice of neurology is heard on Capitol Hill. It is emailed to US members twice monthly and is posted at AAN.com/view/HillReport. Below are some recent highlights.
AAN to Congress: Repeal IPAB Congress took a break for the Fourth of July. So, nothing moved on either side of the Capitol, but deadlines are looming. One is implementation of the Independent Payment Advisory Board (IPAB) that passed as part of the Affordable Care Act in 2010. nn The AAN joined more than 700 organizations and sent a letter to all
members of Congress calling on them to repeal IPAB. nn Although the board has not been appointed, IPAB will be charged with
making recommendations to cut Medicare expenditures if spending growth reaches an arbitrary level. The AAN believes those levels will be hit soon. nn If the IPAB has not been appointed, the Secretary of Health and Human
Services (HHS) is required to implement cuts in physician payments that are not subject to administrative or judicial review. Congress can overturn the action, but only by passing equal cuts in other federal spending.
FAST Act Update Since the last Capitol Hill Report update, the Senate version of the Furthering Access to Stroke Telemedicine (FAST) Act, S. 431, by Sen. John Thune (R-SD) gained Sen. Chris Coons (D-DE) as a cosponsor, bringing the total to 10. The House version of FAST, H.R. 1148, by Rep. Morgan Griffith (R-VA) gained 21 cosponsors, bringing the total to 111 with the addition of: Rep. Bruce Poliquin (R-ME) Rep. Stephen Knight (R-CA) Rep. Steve Stivers (R-OH) Rep. Adam Kinzinger (R-IL) Rep. Tom Rice (R-SC) Rep. Diana DeGette (D-CO) Rep. Alan Lowenthal (D-CA) Rep. David Cicilline (D-RI) Rep. Chris Stewart (R-UT) Rep. Christopher Smith (R-NJ) Rep. Judy Chu (D-CA) Rep. Jody Hice (R-GA) Rep. Jamie Raskin (D-MD) Rep. Elizabeth Esty (D-CT)
Rep. David Young (R-IA) Rep. Paul Cook (R-CA) Rep. Henry Cuellar (D-TX) Rep. Steve King (R-IA) Rep. Steve Cohen (D-TN) Rep. Raul Ruiz (D-CA) Rep. Bob Goodlatte (R-VA)
nn The FAST Act has passed the Senate Finance Committee as part of the CHRONIC Care Act. nn House Energy and Commerce Committee staff have indicated that the FAST Act is on the list for a
potential hearing in the future. nn In the 115th Congress, 4,564 bills have been introduced as of July 7. The FAST Act is one of just 83 (1.8%)
that have more than 100 cosponsors.
News and Notes nn AAN member David Irwin, MD, of the University of Pennsylvania, provided an overview of his aging
and neuroscience research at a Capitol Hill briefing last week entitled “Advancing the Health of an Aging Population: Groundbreaking Research Supported by the NIA.” nn The AAN joined over 100 organizations in signing on to a letter supporting S. 794, the Local Coverage
Determination Clarification Act of 2017, a bill that improves transparency and accountability when Medicare contractors set local coverage determination policies. •
AANnews • August 2017
Bike Helmet Giveaway Protects Thousands of Twin Cities Brains Twin Cities cyclists came spinning by the AAN’s Minneapolis headquarters for the sixth annual bike helmet giveaway in June. Academy volunteer staff fitted and distributed 1,000 brain buckets to bikers of all ages—and head sizes. At times, the line of polite pedalers perambulated nearly two blocks around the Academy’s building as people waited patiently for their free helmet. AAN President Ralph L. Sacco, MD, MS, FAHA, FAAN, who was on-site for the summer meeting of the AAN Board of Directors, spoke to a reporter from local CBS affiliate WCCO-TV about the importance of protecting the brain from concussion, whether while participating in a sports activity or wheeling through the streets. The public also had the opportunity to play on the AAN-hosted piano from Pianos on Parade, a Minneapolis Downtown Council program to promote interaction with the city in creative ways. Visitors took pictures with their helmets in a photo booth for posting to friends on social media. And,
in honor of the event, Minneapolis Mayor Betsy Hodges proclaimed Brain Health Awareness Day in the city to raise awareness about brain health. To extend its impact on Minnesotans’ brain health, the AAN has donated an additional 1,100 helmets to local non-profit organizations including the Minneapolis Police Department Bike Cops for Kids, SPOKES/Cycles for Change, St. PaulRamsey County Public Health, Extended Learning Summer School/Minneapolis Public Schools, Brain Injury Alliance Minnesota and Hennepin County Health Care for the Homeless. •
Report Examines Work-life Balance Issues for Residents and Fellows Seven out of 10 neurology residents and five of 10 neurology fellows have one or more symptoms of burnout, according to a large study by the AAN that was published online in Neurology ® on July 5 and in print in the August 1, 2017, issue of the journal. “This study provides important insights into factors associated with increased burnout for neurology Kerry H. Levin, MD, FAAN trainees and is an important tool as the AAN continues to be a leader in identifying and creating mitigation strategies to reduce burnout,” said Kerry H. Levin, MD, FAAN, of the Cleveland Clinic in Ohio. The study found that burnout is common, with 73 percent of residents and 55 percent of fellows having at least one symptom. A previous examination of data from practicing neurologists found that overall, 60 percent of neurologists experience burnout.
Some key findings include: nn Residents worked 68 hours a week compared to 59
hours for fellows. nn Residents spent 83 percent of their time on patient care
compared to 67 percent for fellows. nn Residents devoted four percent of their time to research
compared to 19 percent for fellows. nn Residents cared for an average of 10 inpatients on
hospital days compared to one for fellows. nn Residents also spent an average of 23 weekends per year
rounding in the hospital compared to four for fellows. nn 58 percent of residents had a high score for emotional
exhaustion compared with 46 percent for fellows. For residents, greater satisfaction with work-life balance and meaning in work were associated with a lower risk of burnout. For fellows, it was greater satisfaction with work-life balance and effective support staff. The finding that residents experienced significantly more burnout was mainly attributable to increased depersonalization. Greater career satisfaction was also more likely for those working in the Midwest compared with the Northeast regions. Also of note, study participants were surveyed after the implementation of work hour restrictions so despite those restrictions, the rate of trainee burnout is still high. To learn more about tips, tools and strategies to help mitigate burnout, visit AAN.com/LiveWell. •
Task Force Recommends Book on Implicit Bias As part of its efforts to educate members on implicit bias and strategies to combat it, the AAN’s Gender Disparity Task Force is recommending to members the book Blindspot: Hidden Biases of Good People by Mahzarin R. Banaji and Anthony G. Greenwald. “This book focuses on the perceptions that we all have that affect our judgments without our awareness, including people with good intentions who are not consciously intending to show bias or favoritism,” said Charles C. Flippen II, MD, FAAN, secretary-treasurer of the AAN Institute, who recommended the book to the AAN and AAN Institute Boards of Directors. “I wholeheartedly recommend this book to any member seeking to examine how hidden biases may be at play in their practices and their everyday lives.”
Charles C. Flippen II,
Elaine C. Jones,
MD, FAAN MD, FAAN Elaine C. Jones, MD, FAAN, chair of the Gender Disparity Task Force, said, “With the alarming news that the salary disparity between men and women in academic medicine is largest in neurology, we have realized that we need to work collectively and individually to address this issue. As the AAN works to implement the recommendations of the task force, I invite all of you to take action as well, and this book is a great first step.”
The Blindspot book and website include the Implicit Association Test that allows people to recognize their own biases. For more information, visit Blindspot.fas.harvard.edu. •
AANnews • August 2017
QUIETING MS Quietly
for your patients with relapsing MS
*AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Overall discontinuation rates due to adverse events were 12.5% with AUBAGIO 14 mg, 11.2% with AUBAGIO 7 mg, and 7.5% with placebo, and treatment discontinuation rates due to common adverse events were ≤3.3% in the pooled clinical trials.1,2
INDICATION AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis. IMPORTANT SAFETY INFORMATION WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY • Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. • Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug-induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or activated charcoal. AUBAGIO is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO. • AUBAGIO is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposure lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant. Please see additional Important Safety Information and Brief Summary of Full Prescribing Information, including boxed WARNING, on the following pages.
THINK BEYOND RELAPSES IN THE MANAGEMENT OF RMS
MAKE AN IMPACT ON DISABILITY PROGRESSION NOW TRE
IMPORTANT SAFETY INFORMATION (continued) CONTRAINDICATIONS • Patients with severe hepatic impairment. • Pregnant women and females of reproductive potential not using effective contraception. • Patients with a history of hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO. • Co-administration with leflunomide. WARNINGS AND PRECAUTIONS • Hepatotoxicity: Patients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine). • Teratogenicity: AUBAGIO may cause fetal harm when administered in pregnant women. Teratogenicity and embryo-fetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum human recommended dose of 14 mg/day. AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2. • Procedure for Accelerated Elimination of Teriflunomide: Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or activated charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.
Please see additional Important Safety Information and Brief Summary of Full Prescribing Information, including boxed WARNING regarding hepatotoxicity and use in pregnancy, on the following pages.
Start or switch to AUBAGIO (teriflunomide) 14 mg—the only oral DMT with a proven impact on disability progression in 2 Phase III trials ®
The majority of patients remained free from disability progression* with AUBAGIO 14 mg1
80 84 AN ESTIMATED
OVER 108 WEEKS (P =0.03)1†
OVER 108 WEEKS (P <0.05)1†
DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; RMS=relapsing forms of MS. *Disability progression was a secondary endpoint in TEMSO and TOWER.6,7 † Based on Kaplan-Meier estimates.1 TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.6 TOWER: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1169). Patients were randomized to receive AUBAGIO 14 mg (n=372), AUBAGIO 7 mg (n=408), or placebo (n=389) once daily with results for up to 40 months of treatment.7
• The estimated proportion of patients with sustained disability progression: —TEMSO: 20.2%, 21.7%, and 27.3% with AUBAGIO 14 mg, AUBAGIO 7 mg, and placebo, respectively1 —TOWER: 15.8%, 21.1%, and 19.7% with AUBAGIO 14 mg, AUBAGIO 7 mg, and placebo, respectively1 • AUBAGIO 7 mg did not achieve a statistically significant reduction in risk of sustained disability progression versus placebo in either trial1 • Sustained disability progression was defined as at least a 1-point increase from baseline EDSS score ≤5.5 (or at least a 0.5-point increase for those with a baseline EDSS score >5.5) sustained for at least 12 weeks1 • AUBAGIO 14 mg and 7 mg achieved a significant relative reduction in risk of relapse in TEMSO (31% for both doses; P<0.05) and TOWER (36% and 22%, respectively; P<0.05)1
• Bone Marrow Effects/Immunosuppression Potential/Infections: Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Thrombocytopenia, including rare cases with platelet counts less than 50,000/mm3, has been reported in the postmarketing setting. Obtain a complete blood cell count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide. • Hypersensitivity and Serious Skin Reactions: AUBAGIO can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue. Cases of serious skin reactions, including Stevens-Johnson syndrome and a fatal case of toxic epidermal necrolysis, have been reported with AUBAGIO. Very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms have also been reported with leflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and begin accelerated elimination. In such cases, patients should not be re-exposed to teriflunomide. • Peripheral Neuropathy: Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination. • Increased Blood Pressure: Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment. • Respiratory Effects: Interstitial lung disease (ILD), including acute interstitial pneumonitis, has been reported with AUBAGIO. ILD may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. If discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure. (continued on back)
MAKE AN IMPACT ON DISABILITY PROGRESSION—START OR SWITCH TO AUBAGIO 1
The only oral DMT with a proven impact on disability progression in 2 Phase III trials1,4,5 • An estimated 80% of patients in TEMSO and 84% of patients in TOWER remained free from disability progression over 108 weeks with AUBAGIO® (teriflunomide) 14 mg1 • AUBAGIO 7 mg did not achieve a statistically significant reduction in risk of sustained disability progression versus placebo in either trial1 • Sustained disability progression was defined as at least a 1-point increase from baseline EDSS score ≤5.5 (or at least a 0.5-point increase for those with a baseline EDSS score >5.5) sustained for at least 12 weeks1
AUBAGIO kept a range of RMS patients free from relapse1 • AUBAGIO 14 mg and 7 mg achieved a significant relative reduction in risk of relapse in TEMSO (31% for both doses; P<0.05) and TOWER (36% and 22%, respectively; P<0.05)
One pill, once a day, taken with or without food1
• Health care professionals should run certain tests before prescribing AUBAGIO and should monitor patient liver enzyme levels monthly for the first 6 months
AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Overall discontinuation rates due to adverse events were 12.5% with AUBAGIO 14 mg, 11.2% with AUBAGIO 7 mg, and 7.5% with placebo, and treatment discontinuation rates due to common adverse events were ≤3.3% in the pooled clinical trials.1,2
IMPORTANT SAFETY INFORMATION (continued) Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%). Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters. Use in Specific Populations: Women who wish to become pregnant should discontinue AUBAGIO and undergo an accelerated elimination procedure. Use of effective contraception should be continued until plasma concentrations of teriflunomide are <0.02 mcg/mL. Nursing mothers should not use AUBAGIO. AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue therapy and either undergo accelerated elimination or verify plasma teriflunomide concentration is <0.02 mcg/mL. Please see additional Important Safety Information on the previous pages and Brief Summary of Full Prescribing Information, including boxed WARNING regarding hepatotoxicity and use in pregnancy, on the following pages. References: 1. AUBAGIO (teriflunomide) [package insert]. Cambridge, MA: Genzyme Corporation; November 2016. 2. Data on file, Sanofi/Genzyme. Summary of safety HMR1726teriflunomide. December 5, 2013. 3. Ziemssen T, De Stefano N, Pia Sormani M, Van Wijmeersch B, Wiendl H, Kieseier BC. Optimizing therapy early in multiple sclerosis: An evidence-based view. Mult Scler Relat Disord. 2015;4(5):460-469. 4. Tecfidera (dimethyl fumarate) [package insert]. Cambridge, MA: Biogen Inc.; February 2016. 5. Gilenya (fingolimod) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2016. 6. O’Connor P, Wolinsky JS, Confavreux C, et al; for the TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293-1303. 7. Confavreux C, O’Connor P, Comi G, et al; for the TOWER Trial Group. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(3):247-256.
©2017 Genzyme Corporation. All rights reserved. AUBAGIO, Sanofi, and Genzyme registered in U.S. Patent and Trademark Office. GZUS.AUBA.15.01.0246(4) February 2017
AUBAGIO® (teriflunomide) tablets, for oral use
Brief Summary of Prescribing Information WARNING: HEPATOTOXICITY and RISK OF TERATOGENICITY • Hepatotoxicity Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for six months after starting AUBAGIO [see Warnings and Precautions (5.1)]. If drug induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or charcoal [see Warnings and Precautions (5.3)]. AUBAGIO is contraindicated in patients with severe hepatic impairment [see Contraindications (4)]. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO. • Risk of Teratogenicity AUBAGIO is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant [see Contraindications (4), Warnings and Precautions (5.2, 5.3), Use in Specific Populations (8.1), and Clinical Pharmacology (12.3) in the full prescribing information].
1 INDICATIONS AND USAGE AUBAGIO® is indicated for the treatment of patients with relapsing forms of multiple sclerosis. 2 DOSAGE AND ADMINISTRATION The recommended dose of AUBAGIO is 7 mg or 14 mg orally once daily. AUBAGIO can be taken with or without food. Monitoring to assess safety • Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for six months after starting AUBAGIO [see Warnings and Precautions (5.1)]. • Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with AUBAGIO. Further monitoring should be based on signs and symptoms of infection [see Warnings and Precautions (5.4)]. • Prior to initiating AUBAGIO, screen patients for latent tuberculosis infection with a tuberculin skin test or blood test for mycobacterium tuberculosis infection [see Warnings and Precautions (5.4)]. • Exclude pregnancy prior to initiation of treatment with AUBAGIO in females of reproductive potential [see Warnings and Precautions (5.2)]. • Check blood pressure before start of AUBAGIO treatment and periodically thereafter [see Warnings and Precautions (5.7)]. 4 CONTRAINDICATIONS AUBAGIO is contraindicated in/with: • Patients with severe hepatic impairment [see Warnings and Precautions (5.1)]. • Pregnant women and females of reproductive potential not using effective contraception. AUBAGIO may cause fetal harm [see Warnings and Precautions (5.2 and 5.3) and Use in Specific Populations (8.1)]. • Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions (5.5)]. • Coadministration with leflunomide [see Clinical Pharmacology (12.3) in the full prescribing information]. 5 WARNINGS AND PRECAUTIONS 5.1 Hepatotoxicity Severe liver injury including fatal liver failure and dysfunction has been reported in some patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. AUBAGIO is contraindicated in patients with severe hepatic impairment [see Contraindications (4)]. In placebo-controlled trials, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving AUBAGIO 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment. Half of the cases returned to normal without drug discontinuation. In clinical trials, if ALT elevation was greater than three times the ULN on two consecutive tests, AUBAGIO was discontinued and patients underwent an accelerated elimi-
nation procedure [see Warnings and Precautions (5.3)]. Of the patients who underwent discontinuation and accelerated elimination in controlled trials, half returned to normal or near normal values within 2 months. One patient in the controlled trials developed ALT 32 times the ULN and jaundice 5 months after initiation of AUBAGIO 14 mg treatment. The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure. AUBAGIO-induced liver injury in this patient could not be ruled out. Obtain serum transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for six months after starting AUBAGIO. Consider additional monitoring when AUBAGIO is given with other potentially hepatotoxic drugs. Consider discontinuing AUBAGIO if serum transaminase increase (greater than three times the ULN) is confirmed. Monitor serum transaminase and bilirubin on AUBAGIO therapy, particularly in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. If liver injury is suspected to be AUBAGIO-induced, discontinue AUBAGIO and start an accelerated elimination procedure [see Warnings and Precautions (5.3)] and monitor liver tests weekly until normalized. If AUBAGIO-induced liver injury is unlikely because some other probable cause has been found, resumption of AUBAGIO therapy may be considered. 5.2 Teratogenicity AUBAGIO may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-fetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum human recommended dose (MHRD) of 14 mg/day [see Use in Specific Populations (8.1)]. AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception [see Contraindications (4) and Warnings and Precautions (5.3)]. 5.3 Procedure for Accelerated Elimination of Teriflunomide Teriflunomide is eliminated slowly from the plasma [see Clinical Pharmacology (12.3) in the full prescribing information]. Without an accelerated elimination procedure, it takes on average 8 months to reach plasma concentrations less than 0.02 mg/L, although because of individual variations in drug clearance it may take as long as 2 years. An accelerated elimination procedure could be used at any time after discontinuation of AUBAGIO. Elimination can be accelerated by either of the following procedures: • Administration of cholestyramine 8 g every 8 hours for 11 days. If cholestyramine 8 g three times a day is not well tolerated, cholestyramine 4 g three times a day can be used. • Administration of 50 g oral activated charcoal powder every 12 hours for 11 days. If either elimination procedure is poorly tolerated, treatment days do not need to be consecutive unless there is a need to lower teriflunomide plasma concentration rapidly. At the end of 11 days, both regimens successfully accelerated teriflunomide elimination, leading to more than 98% decrease in teriflunomide plasma concentrations. Use of the accelerated elimination procedure may potentially result in return of disease activity if the patient had been responding to AUBAGIO treatment. 5.4 Bone Marrow Effects/Immunosuppression Potential/Infections Bone Marrow Effects A mean decrease compared to baseline in white blood cell (WBC) count of approximately 15% (mainly neutrophils and lymphocytes) and in platelet count of approximately 10% was observed in placebo-controlled trials with 7 mg and 14 mg of AUBAGIO. The decrease in mean WBC count occurred during the first 6 weeks and WBC count remained low during treatment. In placebo-controlled studies, neutrophil count <1.5×109/L was observed in 12% and 16% of patients receiving AUBAGIO 7 mg and 14 mg, respectively, compared with 7% of patients receiving placebo; lymphocyte count <0.8× 109/L was observed in 10% and 12% of patients receiving AUBAGIO 7 mg and 14 mg, respectively, compared with 6% of patients receiving placebo. No cases of serious pancytopenia were reported in premarketing clinical trials of AUBAGIO but rare cases of pancytopenia and agranulocytosis have been reported in the postmarketing setting with leflunomide. A similar risk would be expected for AUBAGIO [see Clinical Pharmacology (12.3) in the full prescribing information]. Cases of thrombocytopenia with AUBAGIO, including rare cases with platelet counts less than 50,000/mm3, have been reported in the postmarketing setting. Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with AUBAGIO. Further monitoring should be based on signs and symptoms suggestive of bone marrow suppression. Risk of Infection / Tuberculosis Screening Patients with active acute or chronic infections should not start treatment until the infection(s) is resolved. If a patient develops a serious infection consider suspending treatment with AUBAGIO and using an accelerated elimination procedure. Reassess the benefits and risks prior to resumption of therapy. Instruct patients receiving AUBAGIO to report symptoms of infections to a physician. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections. Medications like AUBAGIO that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections. In placebo-controlled studies of AUBAGIO, no overall increase in the risk of serious infections was observed with AUBAGIO 7 mg (2.2%) or 14 mg (2.7%) compared to placebo (2.2%). However, one fatal case of klebsiella pneumonia sepsis occurred in a patient taking AUBAGIO 14 mg for 1.7 years. Fatal infections have been reported in the postmarketing setting in patients receiving leflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid disease, may predispose patients to infection. In clinical studies with AUBAGIO, cytomegalovirus hepatitis reactivation has been observed. In clinical studies with AUBAGIO, cases of tuberculosis have been observed. Prior to initiating AUBAGIO, screen patients for latent tuberculosis infection with a tuberculin skin test or with a blood test for mycobacterium tuberculosis infection. AUBAGIO has not been studied in patients with a positive tuberculosis screen, and the safety of AUBAGIO in individuals with latent tuberculosis infection is unknown. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with AUBAGIO.
Vaccination No clinical data are available on the efficacy and safety of live vaccinations in patients taking AUBAGIO. Vaccination with live vaccines is not recommended. The long half-life of AUBAGIO should be considered when contemplating administration of a live vaccine after stopping AUBAGIO. Malignancy The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppressive medications. There is a potential for immunosuppression with AUBAGIO. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the AUBAGIO clinical trials, but larger and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with AUBAGIO. 5.5 Hypersensitivity and Serious Skin Reactions AUBAGIO can cause anaphylaxis and severe allergic reactions [see Contraindications (4)]. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue. Cases of serious skin reactions, including cases of Stevens-Johnson syndrome (SJS) and a fatal case of toxic epidermal necrolysis (TEN), have been reported with AUBAGIO. In patients treated with leflunomide, the parent compound, very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Inform patients of the signs and symptoms of anaphylaxis and angioedema and signs and symptoms that may signal a serious skin reaction. Inform patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, or hepatic dysfunction) may be drug-related. Instruct patients to discontinue AUBAGIO and seek immediate medical care should these signs and symptoms occur. Discontinue AUBAGIO, unless the reactions are clearly not drug-related, and begin an accelerated elimination procedure immediately [see Warnings and Precautions (5.3)]. In such cases, patients should not be re-exposed to teriflunomide [see Contraindications (4)]. 5.6 Peripheral Neuropathy In placebo-controlled studies, peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), occurred more frequently in patients taking AUBAGIO than in patients taking placebo. The incidence of peripheral neuropathy confirmed by nerve conduction studies was 1.4% (13 patients) and 1.9% (17 patients) of patients receiving 7 mg and 14 mg of AUBAGIO, respectively, compared with 0.4% receiving placebo (4 patients). Treatment was discontinued in 0.7% (8 patients) with confirmed peripheral neuropathy (3 patients receiving AUBAGIO 7 mg and 5 patients receiving AUBAGIO 14 mg). Five of them recovered following treatment discontinuation. Not all cases of peripheral neuropathy resolved with continued treatment. Peripheral neuropathy also occurred in patients receiving leflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. If a patient taking AUBAGIO develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing AUBAGIO therapy and performing an accelerated elimination procedure [see Warnings and Precautions (5.3)]. 5.7 Increased Blood Pressure In placebo-controlled studies, the mean change from baseline to the end of study in systolic blood pressure was +2.3 mmHg and +2.7 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.6 mmHg for placebo. The change from baseline in diastolic blood pressure was +1.4 mmHg and +1.9 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.3 mmHg for placebo. Hypertension was an adverse reaction in 3.1% and 4.3% of patients treated with 7 mg or 14 mg of AUBAGIO compared with 1.8% for placebo. Check blood pressure before start of AUBAGIO treatment and periodically thereafter. Elevated blood pressure should be appropriately managed during treatment with AUBAGIO. 5.8 Respiratory Effects Interstitial lung disease, including acute interstitial pneumonitis, has been reported with AUBAGIO in the postmarketing setting. Interstitial lung disease and worsening of pre-existing interstitial lung disease have been reported during treatment with leflunomide. Interstitial lung disease may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and for further investigation as appropriate. If discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure [see Warnings and Precautions (5.3)]. 5.9 Concomitant Use with Immunosuppressive or Immunomodulating Therapies Coadministration with antineoplastic, or immunosuppressive therapies used for treatment of multiple sclerosis has not been evaluated. Safety studies in which AUBAGIO was concomitantly administered with other immune modulating therapies for up to one year (interferon beta, glatiramer acetate) did not reveal any specific safety concerns. The long term safety of these combinations in the treatment of multiple sclerosis has not been established. In any situation in which the decision is made to switch from AUBAGIO to another agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds. Use of an accelerated elimination procedure may decrease this risk, but may also potentially result in return of disease activity if the patient had been responding to AUBAGIO treatment [see Warnings and Precautions (5.3)]. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the prescribing information: • Hepatotoxicity [see Contraindications (4) and Warnings and Precautions (5.1)] • Bone Marrow Effects/Immunosuppression Potential/Infections [see Warnings and Precautions (5.4)] • Hypersensitivity and Serious Skin Reactions [see Contraindications (4) and Warnings and Precautions (5.5)] • Peripheral Neuropathy [see Warnings and Precautions (5.6)] • Increased Blood Pressure [see Warnings and Precautions (5.7)]
AUBAGIO® (teriflunomide) tablets, for oral use • Respiratory Effects [see Warnings and Precautions (5.8)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 2047 patients receiving AUBAGIO (7 mg or 14 mg once daily) constituted the safety population in the pooled analysis of placebo controlled studies in patients with relapsing forms of multiple sclerosis; of these, 71% were female. The average age was 37 years. Table 1 lists adverse reactions in placebo-controlled trials with rates that were at least 2% for AUBAGIO patients and also at least 2% above the rate in placebo patients. The most common were headache, an increase in ALT, diarrhea, alopecia, and nausea. The adverse reaction most commonly associated with discontinuation was an increase in ALT (3.3%, 2.6%, and 2.3% of all patients in the AUBAGIO 7 mg, AUBAGIO 14 mg, and placebo treatment arms, respectively). Table 1. Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Sclerosis AUBAGIO AUBAGIO 7 mg 14 mg Placebo Adverse Reaction (N=1045) (N=1002) (N=997) Headache 18% 16% 15% Increase in Alanine aminotransferase 13% 15% 9% Diarrhea 13% 14% 8% Alopecia 10% 13% 5% Nausea 8% 11% 7% Paresthesia 8% 9% 7% Arthralgia 8% 6% 5% Neutropenia 4% 6% 2% Hypertension 3% 4% 2% Cardiovascular Deaths Four cardiovascular deaths, including three sudden deaths, and one myocardial infarction in a patient with a history of hyperlipidemia and hypertension were reported among approximately 2600 patients exposed to AUBAGIO in the premarketing database. These cardiovascular deaths occurred during uncontrolled extension studies, one to nine years after initiation of treatment. A relationship between AUBAGIO and cardiovascular death has not been established. Acute Renal Failure In placebo-controlled studies, creatinine values increased more than 100% over baseline in 8/1045 (0.8%) patients in the 7 mg AUBAGIO group and 6/1002 (0.6%) patients in the 14 mg AUBAGIO group versus 4/997 (0.4%) patients in the placebo group. These elevations were transient. Some elevations were accompanied by hyperkalemia. AUBAGIO may cause acute uric acid nephropathy with transient acute renal failure because AUBAGIO increases renal uric acid clearance. Hypophosphatemia In clinical trials, 18% of AUBAGIO-treated patients had hypophosphatemia with serum phosphorus levels of at least 0.6 mmol/L, compared to 7% of placebo-treated patients; 4% of AUBAGIO-treated patients had hypophosphatemia with serum phosphorus levels at least 0.3 mmol/L but less than 0.6 mmol/L, compared to 0.8% of placebo-treated patients. No patient in any treatment group had a serum phosphorus below 0.3 mmol/L. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AUBAGIO. 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. • Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema [see Warnings and Precautions (5.5)] • Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome [see Warnings and Precautions (5.5)] • Thrombocytopenia [see Warnings and Precautions (5.4)] • Interstitial lung disease [see Warnings and Precautions (5.8)] • Pancreatitis 7 DRUG INTERACTIONS Effect of AUBAGIO on CYP2C8 substrates Teriflunomide is an inhibitor of CYP2C8 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3) in the full prescribing information]. Effect of AUBAGIO on warfarin Coadministration of AUBAGIO with warfarin requires close monitoring of the international normalized ratio (INR) because AUBAGIO may decrease peak INR by approximately 25%. Effect of AUBAGIO on oral contraceptives AUBAGIO may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with AUBAGIO [see Clinical Pharmacology (12.3) in the full prescribing information]. Effect of AUBAGIO on CYP1A2 substrates Teriflunomide may be a weak inducer of CYP1A2 in vivo. In patients taking AUBAGIO, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3) in the full prescribing information].
Effect of AUBAGIO on organic anion transporter 3 (OAT3) substrates Teriflunomide inhibits the activity of OAT3 in vivo. In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3) in the full prescribing information]. Effect of AUBAGIO on BCRP and organic anion transporting polypeptide B1 and B3 (OATP1B1/ 1B3) substrates Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo. For a patient taking AUBAGIO, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking AUBAGIO [see Clinical Pharmacology (12.3) in the full prescribing information]. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AUBAGIO during pregnancy. Healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2 Risk Summary AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of the potential for fetal harm based on animal data. Human data are not available at this time to inform the presence or absence of drug-associated risk with the use of AUBAGIO during pregnancy. In animal reproduction studies in rat and rabbits, oral administration of teriflunomide during organogenesis caused teratogenicity and embryolethality at plasma exposures (AUC) lower than that at the maximum human recommended dose (MHRD) of 14 mg/day [see Data]. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. Clinical Considerations Women who wish to become pregnant should discontinue use of AUBAGIO and undergo an accelerated elimination procedure to decrease the plasma concentration of teriflunomide to less than 0.02 mg/L (0.02 mcg/mL). Effective contraception should be used until is it verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions (5.3)]. Human plasma concentrations of teriflunomide less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryofetal risk [see Contraindications (4) and Warnings and Precautions (5.3)]. If the patient becomes pregnant while taking this drug, stop treatment with AUBAGIO, inform the patient of the potential risk to the fetus, and perform the accelerated drug elimination procedure to achieve plasma concentrations of less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) in the full prescribing information]. Refer the patient to an obstetrician/gynecologist, preferably experienced in reproductive toxicity, for further evaluation and counseling [see Warnings and Precautions (5.2, 5.3)]. Data Animal Data When teriflunomide (oral doses of 1, 3, or 10 mg/kg/day) was administered to pregnant rats throughout the period of organogenesis, high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and embryofetal death were observed at doses not associated with maternal toxicity. Adverse effects on embryofetal development were observed following dosing at various stages throughout organogenesis. Maternal plasma exposure at the no-effect level (1.0 mg/kg/day) for embryofetal developmental toxicity in rats was less than that in humans at the maximum recommended human dose (MRHD, 14 mg /day). Administration of teriflunomide (oral doses of 1, 3.5, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and embryofetal death at doses associated with minimal maternal toxicity. Maternal plasma exposure at the no-effect dose (1.0 mg/kg/day) for embryofetal developmental toxicity in rabbits was less than that in humans at the MRHD. In studies in which teriflunomide (oral doses of 0.05, 0.1, 0.3, 0.6, or 1.0 mg/kg/day) was administered to rats during gestation and lactation, decreased growth, eye and skin abnormalities, and high incidences of malformation (limb defects) and postnatal death were observed in the offspring at doses not associated with maternal toxicity. Maternal plasma exposure at the no-effect dose for pre- and postnatal developmental toxicity in rats (0.10 mg/kg/day) was less than that in humans at the MRHD. In animal reproduction studies of leflunomide, embryolethality and teratogenic effects were observed in pregnant rat and rabbit at or below clinically relevant plasma teriflunomide exposures (AUC). In published reproduction studies in pregnant mice, leflunomide was embryolethal and increased the incidence of malformations (craniofacial, axial skeletal, heart and great vessel). Supplementation with exogenous uridine reduced the teratogenic effects in pregnant mice, suggesting that the mode of action (inhibition of mitochondrial enzyme dihydroorotate dehydrogenase) is the same for therapeutic efficacy and developmental toxicity. At recommended doses in humans, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. 8.2 Lactation Risk Summary It is not known whether this drug is excreted in human milk. Teriflunomide was detected in rat milk following a single oral dose. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AUBAGIO and any potential adverse effects on the breastfed infant from AUBAGIO or from the underlying maternal condition.
AUBAGIO® (teriflunomide) tablets, for oral use 8.3 Females and Males of Reproductive Potential Pregnancy Testing Exclude pregnancy prior to initiation of treatment with AUBAGIO in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.1)]. Contraception Females Females of reproductive potential should use effective contraception while taking AUBAGIO. If AUBAGIO is discontinued, use of contraception should be continued until is it verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL). Females of reproductive potential who wish to become pregnant should undergo an accelerated elimination procedure. Effective contraception should be used until it is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions (5.3)]. Males AUBAGIO is detected in human semen. Animal studies to specifically evaluate the risk of male-mediated fetal toxicity have not been conducted. To minimize any possible risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue use of AUBAGIO and either undergo an accelerated elimination procedure or wait until verification that the plasma teriflunomide concentration is less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions (5.3)]. Infertility Administration of teriflunomide to male rats resulted in no adverse effects on fertility. However, reduced epididymal sperm count was observed [see Nonclinical Toxicology (13.1) in the full prescribing information]. Effects of AUBAGIO on fertility in humans have not been evaluated. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of AUBAGIO did not include patients over 65 years old. 8.6 Hepatic Impairment No dosage adjustment is necessary for patients with mild and moderate hepatic impairment. The pharmacokinetics of teriflunomide in severe hepatic impairment have not been evaluated. AUBAGIO is contraindicated in patients with severe hepatic impairment [see Contraindications (4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3) in the full prescribing information]. 8.7 Renal Impairment No dosage adjustment is necessary for patients with mild, moderate, and severe renal impairment [see Clinical Pharmacology (12.3) in the full prescribing information]. 10 OVERDOSAGE There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects. In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions (5.3)].
Genzyme Corporation 500 Kendall Street Cambridge, MA 02142 A SANOFI COMPANY November 2016 TER-BPLR-SA-NOV16
CME & MOC
Sleep Neurology Is Focus of August Continuum Sleep neurology is examined in this month’s issue of Continuum: Lifelong Learning in Neurology ®. “Sleep has a crucial homeostatic role for normal brain function. This issue should enable neurologists to effectively recognize and treat commonly encountered sleep disorders in neurologic practice, helping them to provide optimal care toward maximizing patient functioning and quality of life,” said guest editor Erik K. St. Louis, MD, MS, FAAN, FAASM, co-director at the Center for Sleep Medicine, associate professor of neurology, and director of the Sleep and Cognitive Neurophysiology Laboratory at Mayo Clinic College of Medicine and Science in Rochester, MN. Articles include: nn Brain Circuitry Controlling Sleep and Wakefulness, by
Richard L. Horner, PhD, and John H. Peever, PhD
nn Diagnostic Approach and Investigation in Sleep Medicine,
by Michael H. Silber, MBChB, FAAN
nn Narcolepsy and Other Central Hypersomnias, by
Yves Dauvilliers, MD, PhD, and Lucie Barateau, MD
nn Restless Legs Syndrome and Sleep-related Movement
Disorders, by Lynn Marie Trotti, MD, MSc
nn Rapid Eye Movement Sleep Behavior Disorder and
Other Rapid Eye Movement Parasomnias, by Birgit Högl, MD, and Alex Iranzo, MD
nn Non–rapid Eye Movement and Overlap Parasomnias, by
Muna Irfan, MD; Carlos H. Schenck, MD; and Michael J. Howell, MD, FAAN
nn Circadian Rhythm Sleep-wake Disorders, by
Milena Pavlova, MD, FAASM
nn Chronic Insomnia Disorder, by Alon Y. Avidan, MD,
MPH, FAAN, and David N. Neubauer, MD
nn Sleep-disordered Breathing, by Nancy R. Foldvary-
Schaefer, DO, MS, and Tina E. Waters, MD
The issue also includes a section on ethical and medicolegal issues Erik K. St. Louis, MD, MS, focused on shared medical decision FAAN, FAASM making in consideration of opioid therapy in a patient with restless legs syndrome, as well as a section on practice issues related to driving safety and sleep medicine coding and coverage guidelines. Participants can earn up to 14 hours of AMA PRA Category 1 Credit™ (12 of which apply to MOC Self-Assessment credit). Canadian participants can earn up to 14 hours of Self-Assessment CME credits to help fulfill Section 3 MOC requirements of the Royal College of Physicians and Surgeons of Canada. Continuum® is published six times per year. Subscribe to Continuum by contacting Wolters Kluwer at (800) 361-0633, (301) 223-2300 (international), or LWW.com/continuum. Junior members who are transitioning to Neurologist memberships can receive a 50-percent discount on the already low member rate for Continuum subscriptions. •
nn Comorbid Sleep Disturbances in Neurologic Disorders,
by Yo-El S. Ju, MD, MSCI; Aleksandar Videnovic, MD, MSc, FAAN, FAASM; and Bradley V. Vaughn, MD, FAAN, FAASM
nn Sleep-wake Disorders of Childhood, by Suresh Kotagal,
Accreditation Granted to 12 New Programs Twelve new fellowship programs have been accredited through the United Council for Neurologic Subspecialties (UCNS), bringing the current number of accredited programs to 187. The new programs are: nn Geriatric Neurology at St. Joseph’s Hospital and
nn Headache Medicine at the University of Rochester
Medical Center, New York University, Children’s Hospital of Philadelphia, and the University of Arizona
nn Neurocritical Care at the University of Florida, University
of Rochester Medical Center, Boston Medical Center, University of Texas Medical Branch Galveston, and Beth Israel Deaconess Medical Center
AANnews • August 2017
nn Neuro-oncology at the Mayo Clinic Rochester and
University of Pittsburgh Medical Center
The next deadline to apply for fellowship accreditation is December 1, 2017. For more information, visit UCNS.org, or contact Amanda Carpenter at email@example.com or (612) 928-6065. •
Practice Track Eligibility Extended for Headache Medicine and Neuroimaging Certifications The United Council for Neurologic Subspecialties (UCNS) recently approved the request for extension of the practice-track eligibility period for its certifications in Headache Medicine and Neuroimaging. The extension requests were submitted by the American Headache Society, AAN Headache Medicine & Facial Pain Section, and the American Society of Neuroimaging. The practice track, often referred to as “grandfathering,” allows a pathway for physicians who have practiced in the subspecialty to qualify for the certification examination after meeting a defined set of criteria. The track for Headache Medicine has been extended to include the 2018 and 2020 certification examinations, and the Neuroimaging practice track eligibility pathway is available through the 2019 certification examination. Following the expiration of the practice track, only UCNS-fellowship trained physicians and faculty are eligible for certification. Currently, the UCNS has 523 certified diplomates and 36 accredited training programs in the field of Headache Medicine, and 206 certified diplomates and five accredited training programs in the field of Neuroimaging. Applications for the 2018 Headache Medicine certification examination will be available in January with an application deadline of April 2, 2018. The examination will take place at Pearson VUE testing centers October 8 through 12, 2018.
Join Neurology’s Global Conversation! Connect with neurologists and neuroscience professionals in your area of interest. Get started at AAN.com/Synapse
Additional information is available in the Eligibility Requirements and Information for Applicants Handbook at UCNS.org, or by contacting Todd Bulson at firstname.lastname@example.org or (612) 928-6067. •
AANnews • August 2017
September 8 Is Last Chance to Save $200 on Fall Conference Registration Continued from cover
Set for October 20 through 22 at The Cosmopolitan of Las Vegas, the Fall Conference is your year-end best bet for the latest clinical advances in neurology from top experts in the field—plus 15.75 CME—in a convenient three-day format. With its all-inclusive registration rate, the conference offers significant value, allowing you access to almost all programming and the ability to come and go from sessions at your convenience. Programs: nn Eight Neurology Update courses
covering a wide range of disorders
nn Six Practice Management programs nn Continuum ®: Test Your Knowledge:
A Multiple-choice Question Review
Learn to Navigate Today’s Health Care Landscape with Leadership Challenges in Practice Course
nn Maintenance of Certification
With the issues facing today’s practicing neurologist, it is essential to develop the leadership skills needed to navigate these challenges. The Leadership University: nn Leadership University: Leadership Leadership Challenges in Practice course, offered on Saturday, October 21, Challenges in Practice during the AAN Fall Conference, will address concerns in the evolving health care environment and provide solutions to maintain steadfast leadership skills nn NEW! Neuro-ophthalmology/ to keep your practice vibrant and successful. The course will cover relationship Neuro-otology Skills Workshop development and communication techniques to successfully negotiate with (additional registration and fee health care systems, insurers, and regulatory agencies; refining analytical skills to required) properly select and implement an economical and useful EHR system; properly Learn more at AAN.com/view/fall. • implementing work flows and processes to increase new sources of revenue; and increasing patient/provider satisfaction while meeting regulatory demands. Public Policy: 17NeuroCompProd Ad—Half Page Horizontal> AN The course is open to all registered attendees. • Session
Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C
77+23+L 35+65+L 21+79L Need Help Seeing New Ways to Improve Your Practice? The latest online 2017 Neurology Compensation and Productivity Report offers eye-opening information to help you succeed. Use the customizable dashboard to compare your practice data to local and national colleagues. Determine if you are being compensated fairly relative to your peers, and use the data to demonstrate your value to payers and deliver quality patient care.
Get better visibility with the 2017 Neurology Compensation and Productivity Report at AAN.com/view/2017NeuroReport.
AANnews • August 2017
Ad Page Solve the case of his lifetime Identifying the link can lead to a crucial diagnosis1-5 Hereditary ATTR amyloidosis is an inherited, rapidly progressive disease that causes sensory-motor polyneuropathy that may be accompanied by autonomic or cardiac symptoms, eventually robbing patients of function—and even their lives. With increased research and development in hATTR amyloidosis, now it is more critical than ever to be aware of red-flag symptom clusters and investigate potential cases.
See the connections at: InvestigateRedFlagSymptoms.com
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References: 1. Conceição I, González-Duarte A, Obici L, et al. “Red-flag” symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21(1):5-9. 2. Hanna M. Novel drugs targeting transthyretin amyloidosis. Curr Heart Fail Rep. 2014;11(1):50-57. 3. Adams D, Coelho T, Obici L, et al. Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study. Neurology. 2015;85(8):675-682. 4. Damy T, Judge DP, Kristen AV, et al. Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122lle hereditary transthyretin amyloidosis. J Cardiovasc Transl Res. 2015;8(2):117-127. 5. Mohty D, Damy T, Cosnay P, et al. Cardiac amyloidosis: updates in diagnosis and management. Arch Cardiovasc Dis. 2013;106(10):528-540.
© 2017 Alnylam Pharmaceuticals, Inc. All rights reserved. 05.2017
We Support Research Because You Support Us Over the last 25 years, donors like Isabella have helped the American Brain Foundation by providing more than $24 million to fund clinical research for young investigators. So far in 2017, the Foundation has raised $3,086,664 to fund research on brain disease, including for new Clinical Research Training Scholarship and Clinician-Science Development Award opportunities in headache, dementia with Lewy bodies, and cognitive aging and age-related memory loss. At the recent AAN Annual Meeting in Boston, the Foundation unveiled the world’s first and only neuroscience crowdfunding platform dedicated to funding brain disease research. Investigators can now share innovative research projects directly with donors, and donors can get to know and understand the research they are making possible. We believe bringing researchers and donors together is the key to defeating brain disease. To learn more and to make a donation, please visit AmericanBrainFoundation.org. •
I support the American Brain Foundation and thank them for everything they do to educate and support people with brain injuries and for all the research they do so that one day they will find a way to cure brain disease. —Isabella Sementilli
Donor Spotlight: Meet Isabella: Young Donor Bakes Cookies for Concussions American Brain Foundation donors are as diverse as the one in six people that brain disease impacts. Take, for instance, 13-year-old Isabella Sementilli, one of the Foundation’s most recent—and youngest—donors. A classroom prank involving the pulling of her chair out from under her as she was about to sit down, and a subsequent accident involving a basketball striking her head as she sat watching a game from the sideline resulted in Isabella suffering post-concussion symptoms and a diagnosis of daily persistent headache and occipital neuralgia. The concussions transformed Isabella’s life. Suddenly, simple, everyday activities like reading, watching television, using a computer, washing her hair, and even chewing brought about extreme
AANnews • August 2017
pain. And favorite hobbies she’d pursued passionately for 10 years—such as tap dance and tennis—became all but impossible. Rather than give up, Isabella was determined to develop new hobbies that would bring about less pain. She learned how to knit and bake, and found great success at both—especially her cookies, which received rave reviews from friends and family. Isabella decided to put her new talent to even better use by selling her popular cookies, which she named “Iznettes,” and donating the proceeds to organizations— including the Foundation—whose missions are to help people like her who suffer from post-concussion symptoms. •
Letâ€™s All Commit To Outsmarting Brain Disease. The American Brain Foundation is the central driving force behind bringing all neurologists, researchers, patients, and caregivers together to help generate funding for and awareness of brain disease.
By examining the whole brain, we get the whole picture. Because we believe itâ€™s all connected. So a cure for one disease could be a cure for others.
Mission: The American Brain Foundation brings researchers and donors together to defeat brain disease. For more information, visit www.AmericanBrainFoundation.org
AAN.com/careers Visit the AAN’s Neurology Career Center to view hundreds of additional jobs and sign up for customized, confidential notifications when positions of interest are added.
Neurohospitals, Neurocritical Care, Vascular & Stroke Neurologists for our South Florida Advanced Neuroscience Network—Miami, Fort Lauderdale, Palm Beach As a network, our strength lies in the ability to provide a continuum of care across all subspecialties of neuroscience. To further enhance and maintain our ability to provide this type of care, we are seeking additional neurologists interested in critical care, stroke and vascular disease, and neuro-hospitalist opportunities to join our team in Miami, Fort Lauderdale and Palm Beach County, Florida. Tenet Florida’s Advanced Neuroscience Network spans across the Miami-Dade, Broward, and Palm Beach tri-county area. The network has grown to include over 50 neurologists in multiple specialties including but not limited to interventional neurologists, neurophysiology, and neurosurgery. Along with a strong team of physicians, the network is comprised of 10 award winning hospitals, many of which are comprehensive stroke centers, and multiple full service outpatient centers. With an established integrated delivery system comprised of highly skilled physicians and hospitals focused on providing a true continuum of care, we can provide not just quality care, but also a feeling of hope to our patients within our care. We achieve these goals with some of the latest technology and protocols to appropriately diagnose and treat a wide range of neurological and neurosurgical conditions in the tri-county area. Across the network many professionals and programs have come together under the Advanced Neuroscience Network with the same core values in mind. Our philosophy is a patientcentered approach which is exemplified throughout the continuum of care. We are also committed to educating our patients, and tending to not only their needs, but the needs of their families as well. We hope you will consider joining our network and assist us in providing quality patient-centered care. Residents and Fellows are welcome to apply. For further information, please submit CV to: Lane Mitnick, Physician Recruiter, Tenet Health System Lane.Mitnick@tenethealth.com General Neurology Clinical Educator Opportunity in Southern California The Department of Neurology at Loma Linda University has created a new position for one or more board-certified/eligible neurologists who are interested in a Clinical Educator career in neurology. We believe that a broad interest in clinical neurology without a fellowship is of value to our program and that
additional subspecialty interests, if present, can co-exist with and enhance our existing subspecialty programs. Subspecialty interests for this position can include EMG/ neuromuscular (fellowship training preferred), epilepsy, functional disorders, movement disorders, neurooncology, neuro-otology, stroke, headache, multiple sclerosis, or dementia. This position will have a flexible balance of both neurology clinics and attending our general neurology teaching ward service, depending on your interest. We are looking for someone with a passion for teaching our neurology residents, fellowships, and medical students and instilling in them a sense of clinical duty, partnership, and whole-person care. Added faculty development in seminars and conferences dedicated to furthering neurology education and teaching are supported and opportunities for clinical research and educational outcomes are available. Our neurology department serves our main academic hospital and clinical practice as well as two regional hospitals (Riverside University Medical Center and LLUMCMurrieta). We are a highly collegial group that balances fulfilling academic careers with lifestyle and family. Loma Linda is located between Los Angeles and Palm Springs with convenient access to beach cities, skiing, hiking, and a variety of other outdoor activities. This region has excellent private and public school systems and our position offers a competitive salary and benefit package. Professorship is commensurate with experience. This is not a J1 Opportunity. Email email@example.com Mid Coast Medical Group BC/BE Neurologist Mid Coast Medical Group is seeking a full-time BC/BE Neurologist. Bring your own interests to join our four Neurologists specializing in multiple sclerosis, movement disorders, epilepsy and neuromuscular disorders. Call is a reasonable 1:4, with a Telestroke program for after-hours emergency stroke care. New graduates and experienced candidates are encouraged to apply. A department of Mid Coast Hospital, Mid Coast Medical Group provides high quality primary and specialty care with more than 100 providers. One of Maine’s newest full service hospitals, Mid Coast Hospital is a 93-bed modern facility with more than 200 providers on its active medical staff. Mid Coast is accredited by The Joint Commission, and is recognized as a Magnet™ facility by the American Nurses Credentialing Center for exceptional nursing and patient care. The hospital promotes a healing environment through the design, as well as its location
on 150-acres of coastal Maine. Part of the Mid Coast– Parkview health family of services, Mid Coast Medical Group offers competitive benefits and compensation package, along with an excellent work environment. Please send CV to Melanie Crowe, Physician Recruiter, at firstname.lastname@example.org or call (207) 406-7872, for more information. Job Alert: General Neurology Physician needed—Kansas City Metropolitan Area A growing neurology physician group part of a large health system in the Kansas City Metropolitan area seeks an exceptional full time general neurologist to join a midsize group of 5 physicians and 1 advanced practice provider. The practice provides a full range of neurology care specializing in neurology consultations, EMGs, and Botox for chronic migraine management. This exciting growth opportunity is a mix of outpatient and inpatient responsibilities. Physician candidate must be BC/BE and must have completed a neurology residency. Ability to do EMGS is required. 2018 Neurology Residents and candidates who require visa sponsorship are welcome to apply. Opportunity highlights: Competitive base salary in the $240K–$275K range which includes a lucrative sign-on bonus and relocation bonus; Full benefits including medical, dental, vision, child care, and retirement; Work alongside a collegial group of neurology physicians; Minimal call—offering work life balance. Interested candidates please contact: Sandra Chavez, Senior Search Consultant, Office: (314) 236.4570, Email: email@example.com. Please reference Position ID 160901 when responding AANnews ® Classified Advertising T he AAN offers a complete package of print, online, and in-person recruitment advertising opportunities. Visit AAN.com/careers for all AAN options, rates, and deadlines.
d copy for the October 2017 print edition of A AANnews must be submitted by September 1, 2017. The same deadline applies to changes/cancellations. he American Academy of Neurology reserves the T right to decline, withdraw, or edit advertisements at its discretion. Every care is taken to avoid mistakes, but the responsibility for clerical or printer errors does not exceed the cost of the ad.
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AANnews • August 2017
Dates and Deadlines
SAVE THE DATES! OCTOBER 20–22, 2017 FALL CONFERENCE
JANUARY 12–15, 2018 BREAKTHROUGHS IN NEUROLOGY
AAN.com/view/17FC SUN 6
AUGUST 1 Webinar: A Guide to Teleneurology: Use It in Your Practice (Register by July 31) AAN.com/view/pmw17
Early Registration Deadline: Fall Conference AAN.com/view/Fall
Application Deadline: 2018 Research Program Opportunities AAN.com/view/ResearchProgram
SEPTEMBER 12 Webinar: Open Your Heart, Open Your Notes: A Guide to Patient Engagement (Register by September 11) AAN.com/view/pmw17
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OCTOBER 10 Webinar: Using the EHR or Axon Registry® to Drive Quality Improvement (Register by October 9) AAN.com/view/pmw17
OCTOBER 16–22 Neurology Career Week AAN.com/careers
OCTOBER 20–22 2017 AAN Fall Conference Las Vegas, NV AAN.com/view/fall
OCTOBER 23 Deadline: Call for Abstracts
OCTOBER 25 Deadline: Call for Awards
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AANnews • August 2017
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Published on Jul 24, 2017