Optimal strategies for treatment discontinuation in MOG antibody-associated disease

The relapse risk following discontinuation of immunomodulatory treatment in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. Evidence suggests that 'at least' 3 months of oral corticosteroids reduces relapse risk after a single attack, and that it may be possible to stop maintenance treatment in relapsing stable disease, but the optimal duration of treatment has yet to be defined. We therefore investigated relapse outcomes following discontinuation of maintenance treatment. We conducted a cohort study of MOGAD patients seen in the Oxford Neuromyelitis Optica Highly Specialised Service between January 2010 and May 2025. Patients with MOGAD who had at least 12 months of follow-up and who commenced and then discontinued maintenance treatment were included. Associations of factors including treatment duration before discontinuation, disease course at discontinuation (after a single attack/monophasic or relapsing course) and MOG IgG1 status on live cell-based assay were investigated. The primary outcome was time-to-relapse following treatment discontinuation. Cox regression was used. We included 190 MOGAD patients with 236 discontinued treatment intervals. There were 150 (63.6%) discontinuations after a single attack and before a first relapse in patients with monophasic disease, and 86 (36.4%) discontinuations in patients with relapsing disease. Most patients used corticosteroids alone [84.7% of immunomodulatory treatment (IT) intervals], and non-steroid ITs were used in 15.2% of IT intervals, either alone or in combination with steroids. Post-discontinuation relapse occurred after 92 (39.0%) discontinuations, at a median time of 5.4 (interquartile range 1.4-20.1) months after treatment cessation. Those who relapsed were more likely to have a relapsing course at the time of discontinuation (50% versus 27.8%, P = 0.001) and a positive/low-positive pre-discontinuation MOG IgG1 result (89.8% versus 71.5%, P = 0.005). In a multivariable analysis, a relapsing course at the time of discontinuation was associated with an elevated relapse risk (hazard ratio 1.95, 95% confidence interval 1.25-3.06, P = 0.003). Overall, prolonged treatment beyond 3 months before discontinuation significantly reduced relapse risk. Optimal treatment durations were estimated to be 10-18 months for patients treated after their first attack and 20-30 months for relapsing patients, after which treatment discontinuation could be considered in patients who were relapse-free on treatment. Identifying the relapse risk when discontinuing maintenance immunomodulatory treatment in MOGAD should aid management decisions in patients presenting with their first attack and also in those on longer-term treatment for relapsing disease. Our findings, from a cohort predominantly treated with steroids, provide evidence to inform joint decision-making for stable patients who are considering treatment cessation.