Moseley, Carson E.

Importance Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures Tocilizumab or satralizumab. Main Outcomes and Measures Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

Background: Epstein–Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. Objectives: POMS participants and controls were recruited from 16 pediatric MS clinics between 1 November 2011 and 1 July 2017. Clinical and demographic information, including history of adenotonsillectomy, EBV serostatus, and HLA-DRB1*15:01:01 status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. Results: The case-control analysis included 359 POMS participants and 560 pediatric controls. Individuals with a history of adenotonsillectomy had a 63% increased odds of MS (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.01–2.64, p = 0.046). Among the 239 POMS participants with available follow-up data, adenotonsillectomy was associated with a twofold increase in annualized relapse rate (adjusted incidence rate ratio (IRR) = 2.00, 95% CI = 1.15–3.48, p = 0.013). Conclusions: Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.