Incidence of Progression Independent of Relapse Activity (PIRA) under platform disease-modifying treatment in multiple sclerosis

BACKGROUND: Comparative data on the impact of platform disease-modifying therapies (DMTs) on Progression Independent of Relapse Activity (PIRA) in patients with remitting-relapsing MS (RRMS) are limited. We compared the risk of PIRA among RRMS patients treated with oral (dimethyl fumarate [DMF] versus teriflunomide [TER]) and injectable (interferon beta [IFN] versus glatiramer acetate [GA]) therapies in a real-world setting. METHODS: We conducted a retrospective study including RRMS patients from the Italian MS Registry treated for ≥ 5 years with DMF, TER, IFN, or GA. PIRA was defined as confirmed disability worsening sustained for ≥ 12 months in the absence of relapses. Propensity score 1:1 matching was applied separately for each comparison. Negative binomial regression and Cox models assessed cumulative PIRA events and time to first PIRA event, respectively. RESULTS: Among 1910 eligible patients, 174 matched pairs were obtained for DMF vs TER and 404 matched pairs for IFN vs GA. No significant differences emerged in the cumulative incidence of PIRA (RR:0.82; 95% CI:0.47-1.40), or time to first PIRA (HR:0.81; 95% CI: 0.47-1.37) in TER- versus DMF-treated patients, as well as in GA- versus IFN-treated patients (RR:1.04; 95% CI:0.74-1.45; HR:0.86; 95% CI:0.63-1.17). In pooled comparison between injectable and oral DMTs, no significant differences emerged (RR:0.79; 95% CI:0.52-1.19; HR:1.06; 95% CI:0.71-1.58). CONCLUSIONS: Platform DMTs showed no statistically significant differences on PIRA. Treatment selection within platform DMTs should therefore rely primarily on safety and tolerability considerations rather than expectations of differential protection against relapse-independent progression.