Effectiveness of escalation versus early high-efficacy therapies on progression independent of relapse activity in multiple sclerosis: a Danish nationwide study
Eliza Varju, Luigi Pontieri, Mie Reith Mahler, Melinda MagyariBackground
The effect of early high-efficacy therapy initiation versus escalation from moderate-efficacy therapy on progression independent of relapse activity (PIRA) in multiple sclerosis remains unclear. This study aimed to compare the treatment strategies on effectiveness against PIRA.
Methods
From the Danish MS Registry, treatment-naïve adult patients with multiple sclerosis started on high-efficacy therapies or moderate-efficacy therapies between 2012 and 2022 were included in this nationwide cohort study. Stabilised inverse probability of treatment weights, derived from propensity scores, were applied to balance confounders and to perform weighted Cox and negative binomial regression models. Patients were followed under an intention-to-treat framework until the latest clinical visit before the data extraction date (2 June 2025). The primary outcome was time to first PIRA; the secondary outcome was annualised relapse rate (ARR).
Results
Among 3316 patients (594 high-efficacy, 2722 moderate-efficacy) with a median follow-up time of 7.4 years (min–max: 1.5–13.4), we found no statistical difference in time to first progression independent of relapse activity with a HR of 0.89, 95% CI 0.59 to 1.36, p=0.60. Early high-efficacy therapy initiation was associated with a 40% reduction in ARR (incidence rate ratio of 0.60, 95% CI 0.46 to 0.77, p<0.001).
Conclusions
In this nationwide cohort study, we found a reduction in relapse activity associated with early initiation of high-efficacy therapies but no statistically significant difference when investigating time to first PIRA. Our findings indicate a therapeutic gap in the current treatment landscape with respect to mitigating PIRA.