The phase 3 MOGwAI trial (NCT05349006) is underway to determine the efficacy of azathioprine as a first-line treatment for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Led by Romain Marignier, MD, PhD, the multicenter study, spanning 14 institutions, aims to enroll 126 patients and monitor them over a 36-month treatment period.
The study, presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), is a randomized, double-blind, placebo-controlled trial. It addresses a critical gap in MOGAD treatment, as current therapeutic guidelines remain unclear after a single event. The hypothesis is that early intervention with azathioprine post-first attack can prevent further relapses and disability accrual.
Trial Design and Endpoints
The MOGwAI trial's primary endpoint is the time to first relapse, comparing azathioprine against placebo over a 3-year randomized period. Secondary endpoints include assessing safety, changes in Expanded Disability Status Scale (EDSS) score, visual acuity worsening from baseline, and quality of life. Exploratory endpoints will examine the dynamics of MRI and MOG-IgG titers.
Patient Eligibility
Eligible participants include adults who experienced a first attack of documented acute demyelinating syndrome of the central nervous system within the previous 3 months. All patients must test positive for MOG-antibodies, confirmed in a centralized lab. Exclusion criteria include hypersensitivity to azathioprine or steroids, active infections or cancer, and seriously impaired hepatic or bone marrow functions.
Azathioprine in MOGAD: Prior Evidence
Azathioprine, an immunosuppressant, has been investigated in observational studies for MOGAD. A meta-analysis of these studies, presented at the 2021 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, indicated that azathioprine significantly reduced the annualized relapse rate (ARR) in MOGAD patients. The meta-analysis, encompassing 9 studies and 127 patients, revealed a standardized mean difference in pre- and post-treatment ARR of -0.828 (95% CI, -1.198 to -0.459; P < .001). However, over one-third of the cohort continued to relapse.
Relapse Probability and Disability Scores
The meta-analysis also showed that the relapse probability among children treated with azathioprine was 48.8% (95% CI, 31.4% to 66.4%), while in adults, it was 50.9% (95% CI, 33.8% to 67.8%). The change in Expanded Disability Status Scale scores was not significant with azathioprine treatment (SMD, –0.807; 95% CI, –1.078 to 0.464; P = .435).
The MOGwAI trial is expected to complete in the first months of 2026 and will provide crucial randomized controlled trial data to inform therapeutic guidelines for MOGAD after a first event.
