Early use of high-efficacy disease-modifying therapies reduces the risk of progression independent of relapse and MRI activity in patients with relapsing-remitting multiple sclerosis

Abstract

Background: Progression independent of relapse and MRI activity (PIRMA) is a major contributor to long-term disability in relapsing-remitting multiple sclerosis (RRMS). In Latin America, limited access to high-efficacy disease-modifying therapies (DMTs) may influence PIRMA risk, but real-world evidence is scarce. We aimed to estimate the causal effect of DMT efficacy on PIRMA in an Argentine cohort. Methods: We conducted a retrospective observational study including 264 adults with RRMS meeting predefined disability follow-up criteria. Treatment exposure was modeled as a time-varying variable (low-efficacy vs moderate-/high-efficacy), applying a 60-day pharmacological lag after treatment switches. To address time-dependent confounding, we used a marginal structural model with overlap weighting and a weighted Cox proportional hazards model. Results: Median age at treatment initiation was 31.5 years, 62.1% were female, and median baseline EDSS was 1.0. Over a median follow-up of 7 years, 26 PIRMA events occurred. Exposure to low- or moderate-efficacy DMTs was associated with a significantly higher risk of PIRMA compared with high-efficacy therapies (HR 7.05; 95% CI 1.15-43.35). Conclusion: Exposure to low-/moderate-efficacy disease-modifying therapies was associated with a substantially higher risk of PIRMA compared with high-efficacy treatments, supporting the potential benefit of early access to high-efficacy therapies in RRMS.