In progressive multiple sclerosis (MS), is the benefit of treatment masked by a delayed onset of effect? This research investigates whether non-significant treatment effects observed in randomized clinical trials (RCTs) for progressive MS could be attributed to a delay in treatment effect, potentially linked to baseline characteristics. Data from two RCTs testing interferon-beta and glatiramer-acetate versus placebo in progressive MS were re-analyzed. A time-dependent Cox model was designed, assuming no treatment effect until time t0 and a constant hazard ratio (HR) after t0. The best-fitting t0 was selected from 0 to 2.5 years. Additionally, the delay was modeled as a function of baseline EDSS and fitted to the merged dataset. The time-dependent Cox model revealed a significant benefit of treatment delayed by t0 = 2.5 years for the SPECTRIMS study (HR = 0.65, p = 0.041) and delayed by t0 = 2 years for the PROMISE study (HR = 0.65, p = 0.044). In the merged dataset, the HR for the EDSS-dependent delayed effect was 0.68 (p < 0.001). These findings will help tailor treatment strategies in progressive MS.
Published in Multiple Sclerosis Journal, this research aligns with the journal's focus on understanding and treating multiple sclerosis. By investigating the potential for delayed treatment effects, the study contributes to improving clinical trial design and treatment strategies for progressive MS, a key topic in the journal's scope of neurological research.