To determine the effectiveness, dose thresholds, and time dependence of maintenance immunotherapies for preventing relapse and confirmed sustained disability (CSD) in Myelin Oligodendrocyte Glycoprotein Antibody-associated Disorder (MOGAD).

Evidence for the efficacy of maintenance immunotherapy in reducing the risk of relapses and disability accrual in MOGAD is limited.

This study was a multicenter observational cohort from Australasia and the UK (n=261; pediatric-onset 72, adult-onset 189; median follow-up 6.1 years). Outcomes were time to next relapse (TTNR; recurrent events) and time to CSD (EDSS ≥2 or permanent visual/sphincter/cognitive deficit). Mixed-effects Andersen–Gill Cox models used time-varying covariates for corticosteroids (≥12.5mg/day), IVIg, B-cell depletion (≥1g/6 months) and steroid-sparing agents, with time-independent covariates for center, age, sex, cohort-enrolment status, onset phenotype, and time-to-treatment strata. Following proportional-hazards diagnostics (Schoenfeld residuals), model-adaptive time interactions were incorporated.

Across 478 relapses (annualized relapse rate 0.26), corticosteroids reduced relapse risk (HR 0.38, p<0.001) with attenuation of efficacy after 6 months. B-cell depletion showed dose-dependent benefit (threshold dosing vs other regimens; HR 0.52, p<0.1). Oral steroid-sparing immunotherapies were not associated with reduced TTNR despite 333 patient-years of on-treatment data. ADEM at onset was associated with lower TTNR risk. For CSD (41% reached the endpoint; median survival time 13.4 years), steroids conferred protection (HR 0.25, p=0.03) with attenuation of efficacy after 4 months. Baseline EDSS≥3 independently predicted CSD (HR 2.30, p=0.04). A no-maintenance subgroup (n=44) had fewer relapses (32% relapsing proportion), lower CSD proportion (24%) and were older and more likely to present with isolated ON, suggesting a more benign course in some individuals.

In MOGAD, corticosteroids prevent relapses and disability, with the strongest effect in the first 3–6 months. Higher cumulative doses of B-cell depleting immunotherapies appear more beneficial, whereas oral steroid-sparing immunotherapies showed no effect. Initial attack severity predicts disability accrual, and a more benign untreated subgroup supports individualized therapy.