Time-dependent divergence in infection risks among patients with multiple sclerosis treated with fumarates versus anti-CD20 monoclonal antibodies

Background: People with multiple sclerosis (pwMS) treated with anti-CD20 monoclonal antibodies have an elevated infection risk, yet long-term comparative data with oral fumarates are limited. Objective: To compare infection incidence, healthcare resource utilization, and relapse outcomes among pwMS receiving fumarate or anti-CD20 therapy for ⩾2 years. Methods: This retrospective propensity-matched (1:2) analysis used US Komodo Health claims (1 January 2016–31 May 2022) for pwMS aged 18–64 years with ⩾2 years of continuous follow-up. Outcomes were assessed using Poisson generalized linear models. Results: A total of 1956 pwMS were matched (fumarates: n = 652; anti-CD20s: n = 1304), with mean follow-up ~3 years. By year 2, the fumarates group had a lower infection rate than anti-CD20s (rate ratio: 0.84; 95% CI: 0.73–0.97; p = 0.016), but the most substantial difference was observed in years 4+, where fumarate-treated patients had a 30% reduction versus anti-CD20s (rate ratio: 0.70; 95% CI: 0.52–0.95; p = 0.021). Conclusions: Fumarate therapy was associated with a lower infection risk versus anti-CD20s. The infection rate in the fumarates group remained relatively stable over time, but it progressively increased in the anti-CD20 group, with the most prominent differences observed at year 4 and beyond.