Multiple Sclerosis (MS) is a disorder of the central nervous system characterized by inflammation, demyelination, and degenerative changes. For chronic conditions requiring a potential lifetime of treatment, treatment discontinuation may result in significant clinical issues, including relapse risk and disease progression. There can be a number of factors contributing to treatment discontinuation, but several studies have demonstrated that adverse events and the lack of efficacy represented by continued disease progression are the leading causes. In MS, patient satisfaction with treatment is essential for sustained persistency and positive long-term health outcomes.
Understanding the long-term safety and efficacy considerations of a potential treatment in a chronic disease such as MS is critical to both patients and providers. The aim of this analysis is to understand the frequency and reason leading to premature treatment discontinuation from the long-term extension for patients on the 20mg of ponesimod.
In the main phase 2 study (B201), a total of 464 subjects were randomized in a 1:1:1:1 ratio to receive ponesimod 10 mg (N=108), ponesimod 20 mg (N=116), ponesimod 40 mg (N=119), or placebo (N=121), resulting in a total of 462/464 (99.6%) treated subjects, of whom 393 completed the 24-week double-blind treatment period. Of the 393 subjects who completed treatment in the core study, subjects were eligible to be enrolled into of the extension study (B202) of three treatment phases (TP1, TP2, and TP3) maintaining the either the same dose or for placebo patients rerandomized to 10, 20 or 40mg (although the 40mg was discontinued after TP1).
As of the 31 March 2019 (8.3 years after initiation), a total of 60.7% of subjects in the 20mg arm had maintained therapy on ponesimod over the course of the study and subsequent extensions. For those patients with premature discontinuations, reasons for discontinuation: 40.4% unknown subject decision, 28.1% tolerability/AE related, 17.5% efficacy related, and 14% other reasons.
Patient satisfaction with treatment is key to ensure adherence in a long-term chronic disease. The retention of over 60% of patients during an 8 year, phase 2 long term extension study suggests a high degree of patient satisfaction with the tolerability, safety and efficacy of ponesimod.