Place of anti-IL6R in the therapeutic strategy in NMOSD-AQP4+, MOGAD, and NMOSD double-seronegative patients

Background: Anti-interleukin-6 receptor (anti-IL6R) therapy has demonstrated efficacy in AQP4 + NMOSD, and emerging evidence suggests a similar benefit in patients with MOGAD. Objectives: This study aimed to evaluate the role of anti-IL6R therapy within the treatment algorithm for both NMOSD and MOGAD. In addition, it investigated whether CSF-IL6 levels could serve as a predictive biomarker for treatment response. Methods: Patients with NMOSD or MOGAD who had received at least one dose of anti-IL6R therapy were identified from the NOMADMUS registry. Relapse incidence and timing were analyzed relative to treatment periods. Survival analyses and correlation assessments were conducted between CSF-IL6 concentrations and relapse occurrence. Results: Among 51 patients, anti-IL6R therapy was mostly employed as a second-line treatment in 51% of cases, with 62.7% of patients having previously received rituximab. Anti-IL6R therapy significantly reduced annualized relapse rate, which was lower during anti-IL6R exposure periods than at 1-year pre-exposure periods for AQP4 + ( n = 25, p = 0.007) and MOGAD ( n = 15, p = 0.003) patients, without a significant effect on EDSS scores. No correlation between CSF-IL6 levels and relapse rates was observed, despite higher CSF-IL6 levels in MOGAD. Conclusions: Anti-IL6R therapy appears effective in reducing disease activity in both NMOSD and MOGAD, particularly in patients previously unresponsive to rituximab.