Disease Course After Anti‐ CD20 Discontinuation in Secondary Progressive Multiple Sclerosis—A Multicenter Long‐Term Longitudinal Study

OBJECTIVE: To describe long-term outcomes after anti-CD20 discontinuation in selected patients with secondary progressive multiple sclerosis (SPMS) who remained without subsequent disease-modifying therapy (DMT). METHODS: We retrospectively analyzed data from four centers in Austria and Switzerland. Inclusion criteria were SPMS, ≥ 2 anti-CD20 cycles, discontinuation without subsequent DMT, and ≥ 36 months follow-up. The primary endpoint was time to first confirmed Expanded Disability Status Scale (EDSS) worsening, defined as a ≥ 0.5-point increase after discontinuation documented at a subsequent routine visit. Secondary endpoints were relapses, MRI activity, and severe infections. No continuation cohort was available. RESULTS: Fifty-five patients were included (61% female). Mean age at anti-CD20 start was 53.5 ± 6.6 years, disease duration 19.3 ± 10.1 years, treatment duration 32.8 ± 16.1 months, and post-discontinuation follow-up 55.1 ± 14.1 months. Mean EDSS increased from 5.9 ± 1.3 before anti CD20, to 6.3 ± 1.3 at discontinuation and 6.9 ± 1.2 at last follow-up. Confirmed EDSS worsening occurred in 31 patients (56%). Hazard analysis suggested an exploratory late increase between 48 and 60 months (p = 0.043) based on small numbers at risk. Relapses occurred in 6 patients (10.9%), MRI activity in 4/35 (11%), and severe infections in 17 (31%). CONCLUSIONS: In this selected SPMS cohort, focal inflammatory activity was uncommon, whereas confirmed EDSS worsening accumulated over long-term follow-up. Because inclusion required ≥ 36 months untreated follow-up, early disease activity may have been underestimated, and apparent stability may have been overestimated. Findings are descriptive and hypothesis-generating and do not establish safety or optimal timing of anti-CD20 discontinuation.