Clinical trials of multiple sclerosis therapies: improvements to demonstrate long-term patient benefit

Background The therapeutic goal for multiple sclerosis ( MS) is to achieve a better long-term outcome. However, since available data come from short-term studies, it is important to review the evidence that current therapies provide long-term benefit. Method and results Long-term data from both registry studies and long-term follow-up studies, and efficacy treatment data were reviewed. Registry data show that the course of MS is predictable after a certain level of disability is reached, indicating that short-term efficacy data from randomized, controlled trials provide evidence of long-term benefit. Long-term studies of patients originally enrolled in pivotal randomized, controlled trials consistently show that delayed or discontinued treatment provides less benefit than continuous therapy. The 16-Year Long-Term Follow-Up Study of interferon beta-1b (IFN beta-1b; Betaferon (R)/Betaseron (R)) therapy had the highest ascertainment of long-term follow-up efforts of the pivotal trials, which led to the currently approved therapies. Disability scores at the start of treatment were predictive of their current disability scores. In addition, this 16-year study showed an excellent safety profile with no unexpected side effects to IFN beta-1b and a lower mortality rate after 16 years compared with those receiving placebo treatment during the pivotal study (6 deaths vs 20 deaths). Conclusion This article reviews the key data and provides recommendations for optimizing clinical studies in MS to demonstrate long-term patient benefit. Multiple Sclerosis 2009; 15: 951-958. http://msj.sagepub.com