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.
Background In acetylcholine receptor (AChR) antibody–positive myasthenia gravis (MG), complement activation is a major mechanism underlying impaired neuromuscular transmission and complement inhibitors are used in clinical practice. In the absence of biomarkers predicting responsiveness to complement inhibitors, this study aimed to identify novel predictors. Methods Serum samples from 14 patients with AChR antibody–positive MG and 10 healthy controls (HCs) were incubated with AChR-expressing HEK293 cells. AChR binding IgG and membrane attack complex (MAC) deposition were quantified by flow cytometry. The correlations of these indices with clinical manifestations were analyzed. Results Patients with MG showed higher mean fluorescence intensity (MFI) than HCs for AChR-bound IgG (median: 4614 vs 172; 95% CI 1588–7451, P < 0.001) and MAC deposition (488 vs 227; 95% CI 59–495, P < 0.001). The MFI of AChR-bound IgG correlated with baseline MG Activities of Daily Living (MG-ADL) scores (Spearman rs = 0.58; 95% CI 0.05–0.85, P = 0.033). Improvement in MG-ADL scores correlated with the MFI of AChR-bound IgG, MAC deposition, and the proportion of AChR-bound IgG+/MAC deposition+ double-positive cells. Responders to complement inhibitors had higher proportions of double-positive cells than non-responders (median: 74% vs 0.2%; 95% CI 15–94, P = 0.022). The MFI values of AChR-bound IgG correlated with disease severity, and the proportion of double-positive cells may represent a potential biomarker of therapeutic response to complement inhibition. Prospective validation is needed to assess its predictive value.
