Comparative Effectiveness of Treatments for Relapse Prevention in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Why clinicians should know about it

• Picked for Neurology (clinical) (paper of the day, 8 October 2026): IVIG reduces relapse risk in MOGAD

Abstract

BACKGROUND AND OBJECTIVES: The most effective treatment strategy to prevent relapses after a first myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) event remains unclear. Our objective was to evaluate the comparative effectiveness of maintenance therapies in preventing relapses in pediatric-onset MOGAD. METHODS: We analyzed prospectively collected data from November 2011 to August 2023 across 13 US pediatric neuroimmunology centers. Eligible patients had demyelinating disease onset before age 18 years, confirmed MOG-IgG positivity through cell-based assay, and negative aquaporin-4 IgG. Maintenance therapies were defined as ≥90 consecutive days of treatment and included IV immunoglobulin (IVIG), anti-CD20 therapy, oral corticosteroids, and other immunosuppressants. Two complementary approaches were used: (1) a primary full-course analysis using time-varying Cox proportional hazards models, adjusted for a priori-selected confounders, accounting for treatment changes throughout the disease course, and (2) a secondary early-course analysis using 1:1 propensity score-matched Cox models for the first qualifying treatment initiated within 90 days of onset, applying an intention-to-treat framework to minimize immortal time bias. RESULTS: Among 312 patients (58% female; mean age at onset 8.9 ± 4.2 years), 145 (46%) experienced at least 1 relapse during a median follow-up of 2.53 years (interquartile range 0.75-5.26). In the full-course analysis, IVIG was associated with a statistically significant 46% reduction in relapse risk (hazard ratio [HR] 0.54; 95% CI 0.31-0.93; p = 0.028). Anti-CD20 therapy (HR 0.98; 95% CI 0.56-1.72), oral corticosteroids (HR 0.86; 95% CI 0.55-1.35), and other immunosuppressants showed no significant association with relapse risk. In the early-course propensity-matched analysis, directional trends favoring IVIG (n = 23 matched pairs; HR 0.29; 95% CI 0.07-1.14; p = 0.076) and anti-CD20 therapy (n = 6 matched pairs; HR 0.34; 95% CI 0.03-3.82; p = 0.38) were observed but did not reach statistical significance, likely due to limited sample sizes. Oral corticosteroids showed a nonsignificant trend toward increased relapse risk in early-course analysis (HR 2.18; 95% CI 0.79-6.31; p = 0.13). Older age at disease onset independently increased relapse hazard (HR 1.67 per year; 95% CI 1.49-1.87; p < 0.001), and prior relapse count was a strong predictor of future relapse risk. DISCUSSION: In this large, prospective, multicenter pediatric MOGAD cohort, IVIG was the only treatment consistently associated with reduced relapse risk across both analytical approaches, supporting its potential role as first-line maintenance therapy. Anti-CD20 therapy showed directional trends warranting further investigation. Key limitations include potential residual confounding by indication and small sample sizes in certain treatment categories. Randomized controlled trials are needed to confirm these findings.

Abstract as published, via PubMed.