Disease-Modifying Therapies for Relapsing Multiple Sclerosis
For over 10 years, the most common treatment practice for patients with multiple sclerosis (MS) has been what is referred to as an escalation approach, which is thought to minimize risk and allow for surveillance of disease activity. This treatment approach begins with a “platform” disease-modifying drug, such as interferon beta or glatiramer acetate, which is used until it becomes ineffective or intolerable. The patient is then treated with a higher-efficacy drug, such as natalizumab. A less commonly used treatment approach in patients with MS is referred to as induction therapy, in which the patient is treated with a highly effective drug for a specific period of time, followed by either observation or a lower-risk maintenance therapy. The benefits of this treatment approach have not yet been established for patients with MS. Results of a small study of patients with relapsing-remitting MS who were treated with a T-lymphocyte–depleting humanized monoclonal antibody (alemtuzumab) showed a significant reduction in the annual relapse rate (P<0.001) and a clinically meaningful (1.2 Expanded Disability Status Score points) reduction in disability at 6 months after treatment, with further improvement in disability seen up to 36 months. The idea was that early treatment led to suppression of a toxic inflammatory environment for neurons and axons, thus preventing demyelination and long-term axonal degeneration. Treating patients with relapsing-remitting MS during this “early window of opportunity” with highly effective therapies may improve the course of their disease. Biomarkers that are predictive of therapeutic response and disease outcomes are needed to identify patients for whom early treatment with highly effective therapy would be most beneficial.
Professor and Chair
We currently have a good number of approved disease-modifying drugs that we can use to treat our patients with MS. Physicians generally follow 1 of the following 2 treatment approaches: escalation therapy and induction therapy. The difference between these approaches is that the former starts with a platform disease-modifying drug and is then switched to a higher-efficacy drug when the platform drug becomes ineffective or intolerable. The less-common induction approach starts treatment with a high-efficacy drug for a specified period of time. One of the most pressing issues right now is the lack of biomarkers or other information to tell us exactly which medication is right for an individual patient. In the meantime, I am influenced by growing data suggesting that there may be a role for the earlier use of so-called highly effective disease-modifying therapies, where the ability to reduce relapses to a greater degree might, in fact, have greater intermediate- and long-term benefits than starting with less-efficacious drugs and then working up from there. So, treating patients with relapsing-remitting MS early—during this early window of opportunity—with highly effective therapies may have a positive impact on the course of their disease.
Coles AJ, Cox A, Le Page E, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253(1):98-108.
Edan G, Le Page E. Induction therapy for patients with multiple sclerosis: why? When? How? CNS Drugs. 2013;27(6):403-409.
Wingerchuk DM, Weinshenker BG. Disease modifying therapies for relapsing multiple sclerosis. BMJ. 2016;354:i3518.
Ziemssen T, Derfuss T, de Stefano N, et al. Optimizing treatment success in multiple sclerosis. J Neurol. 2016;263(6):1053-1065.