Long-term outcomes of alemtuzumab in relapsing–remitting multiple sclerosis: a real-world cohort with particular focus on treatment sequencing after natalizumab

Background The role of alemtuzumab (ALEM) after natalizumab (NTZ) discontinuation in relapsing–remitting multiple sclerosis (RRMS) remains to be better defined in real-world settings. Methods We conducted a retrospective, longitudinal, single-centre cohort study including RRMS patients treated with ALEM. Clinical and MRI evaluations were performed every 6 months. Annualized relapse rate (ARR), and radiological activity were assessed longitudinally. NEDA-3 was evaluated both as an annual interval-specific outcome and as sustained NEDA-3 using Kaplan–Meier analysis. Results Eighty-one patients were included, with a mean follow-up after alemtuzumab of 65 months. In this real-world cohort with long-term follow-up, alemtuzumab was associated with sustained control of inflammatory disease activity in relapsing–remitting multiple sclerosis (mean annualized relapse rate of 0.069, mean annual NEDA-3 proportion of 80.7% from years 2 to 7), while and EDSS modest improvement at month 36 versus baseline ( p = 0.04). Kaplan–Meier analysis estimated that approximately 50% of patients maintained uninterrupted NEDA-3 at 60 months. Radiological activity after ALEM completion was associated with higher ARR in the preceding 6 months (HR 1.94, p < 0.05). Notably, among post-NTZ patients with disease onset after 18.5 years, the mean annual NEDA-3 proportion was 93%. Thirty-six adverse events were reported, including early infections and autoimmune thyroiditis (mean onset 28.0 ± 15.1 months). Conclusions In this real-world cohort, alemtuzumab was associated with sustained control of inflammatory disease activity in RRMS, including in patients previously exposed to natalizumab. These findings support a potential role for alemtuzumab within treatment sequencing strategies after NTZ discontinuation.