Last week I posted my slides in favour of the motion that pwMS in wheelchairs should be included in DMT trials. You were asking to learn more about the motion against, and my opponent during the 'burning debate' at ECTRIMS 2016, Patricia Coyle, kindly agreed to share her slides and some key points of her argument for this Guestpost.
Patricia K. Coyle, MD, FAAN, FANA, is Professor and Vice Chair (Clinical Affairs) of Neurology, and Director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, Stony Brook, New York. She received a BS degree with highest honors from Fordham University, Bronx, New York, and an MD degree from the Johns Hopkins School of Medicine, where she was elected to Alpha Omega Alpha. While at the Johns Hopkins School of Medicine, she completed a residency and chief residency in neurology, followed by a two-year fellowship in neuroimmunology and neurovirology. She then went on to establish a successful research laboratory in addition to building a busy clinical practice at the Stony Brook University Medical Center. Dr. Coyle is the author of numerous articles on clinical and basic research aspects of multiple sclerosis (MS) and neurologic infections and she is recognized as a leading expert on MS and neurologic infections. Her areas of expertise include Lyme disease and neurologic infections, cerebrospinal fluid, therapeutics, and neuroimmunology. Her research has been supported by the National Institutes of Health and other organizations. She is currently involved in a number of therapeutic trials testing new immunotherapies for MS, as well as studies addressing neurologic aspects of Lyme disease. In addition to her busy clinical and research careers, she has held active leadership positions in a number of national and international organizations and academic societies, including the American Academy of Neurology, American Neurological Association, National MS Society, and the American Board of Psychiatry and Neurology, and has been a member of the FDA CNS and PNS Drugs Advisory Panel. She lectures widely on MS and neurologic infections to national and international audiences.
- People with MS in wheelchairs can and should participate in many types of clinical trials (testing CNS repair strategies, symptom management, rehabilitation techniques, national history studies)
- People with MS in wheelchairs have been and are currently routinely excluded from pivotal trials testing progressive MS DMTs
- This exclusion is not based on discrimination; it is done to give the pivotal trial the best chance to be successful
- In such pivotal trials you typically enter much more restricted “idealized” populations to avoid bias of failing to see a treatment effect
- The primary outcome in such trials remains a clinical one, which documents that a drug can slow progression over a short (typically two year) period
- People with MS in wheelchairs are not ideal to show such a time-related change for multiple reasons:
- They typically have had bad MS for a long time, have accumulated a lot of CNS damage, and have the least CNS reserve
- They do not have EDSS in the walking part of the scale, which is where changes are most commonly seen quickly; they are in the EDSS ≥7 range, where EDSS changes slowly if at all
- They have more confounding comorbidities, more symptoms that are not as well managed, less physical exercise tolerance, all of which can interfere with their evaluation
- The two current successful phase III PPMS and SPMS progressive trials both excluded people with MS in wheelchairs
- Once approved, progressive MS DMTs should and in fact must be made available to people with MS in wheelchairs
- Bottom line: for the ultimate higher good, to provide the best chance for critical pivotal progressive treatment trials to be positive, people with MS in wheelchairs must continue to be excluded (but not from the right to be treated)
CoI: PKC has served in a consultancy capacity for Accordant, Bayer, Biogen, Genentech/Roche, Mallinckrodt, Novartis, Sanofi Genzyme, Merck Serono and Teva, and has received research support from Actelion, Genentech/Roche, Novartis and Opexa.