Key Points
Question What is the impact of maintenance therapy discontinuation on relapse risk in patients with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD)?
Findings In this cohort study of 705 adult patients with MOGAD, 83 discontinuations were analyzed, with a1-year relapse risk of 8.7%. Relapse risk was significantly decreased in patients with a prior treatment duration greater than 1 year and a time since last relapse greater than 2 years.
Meaning The findings suggest that treatment discontinuation may be considered in selected adult patients with MOGAD.
Abstract
Importance Therapeutic deescalation strategies are increasingly considered in demyelinating diseases to mitigate the risks associated with prolonged immunosuppression. The impact of treatment discontinuation in myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is not established.
Objective To assess the relapse risk following treatment discontinuation in adult patients with MOGAD and to evaluate factors associated with disease reactivation.
Design, Setting, and Participants This retrospective cohort study including 41 centers was conducted using the French NOMADMUS database. Adult patients with MOGAD diagnosed between January 2013 and April 2024 were included. Data were extracted on July 1, 2024. A total of 1047 patients with MOGAD were screened, and 705 patients fulfilled the inclusion criteria. Among them, 319 (45.2%) received at least 1 maintenance therapy.
Exposure All instances of treatment discontinuation were collected and categorized according to their underlying reasons. Only discontinuations that were scheduled or related to adverse events were analyzed.
Main Outcomes and Measures Time to first relapse was estimated using Kaplan-Meier survival curves, and differences between groups were assessed using the log-rank test.
Results A total of 83 patients (median [IQR] age, 42.7 [28.9-53.3] years; 52 [63.7%] female) discontinued either oral immunosuppressants (azathioprine or mycophenolate mofetil) or rituximab in 60 (72.1%) and 23 (27.7%) individuals, respectively. Discontinuations were scheduled (n = 54 [65.1%]) or related to adverse events (n = 29 [34.9%]). After discontinuation, 7 patients relapsed, with a median (IQR) time to relapse of 0.5 (0.1-1.4) years. The Kaplan-Meier estimated cumulative incidence of relapse at 1 year after discontinuation was 8.7% (95% CI, 1.0-15.9). Severity of relapses was mild, with a median (IQR) change in the Expanded Disability Status Scale score of 0 (0-1) points. Factors associated with an increased relapse risk were a treatment duration of less than 1 year (7 relapses [19.4%] vs 0 relapses; log-rank P = .002) and a time since last relapse of less than 2 years (7 relapses [15.9%] vs 0 relapses; log-rank P = .01).
Conclusions and Relevance The low risk of disease reactivation found in this study suggests that discontinuing treatment may be considered in selected adult patients with MOGAD. Future clinical trials are necessary to confirm these results and establish guidelines in this situation.
Kang YR, Ju H, Kim KH, Choo SH, Ju W, Kim SM, Kim S, Sohn E, Nam TS, Oh SY, Yoon BA, Kim JK, Kim H, Lee EJ, Lim YM, Kwon YN, Kim SW, Shin HY, Kim JE, Joo IS, Park M, Lee HS, Kim BJ, Park JW, Lee SY, Kim W, Hyun JW, Kim SH, Min JH, Kim HJ. Outcomes of immunosuppressive therapy discontinuation in patients with myelin oligodendrocyte glycoprotein antibody-associated disease. Mult Scler. 2025 Aug;31(9):1102-1109. doi: 10.1177/13524585251320046. Epub 2025 Apr 28. PMID: 40296497.
Abstract
Background: Research on the optimal duration of immunosuppressive therapy (IST) and the outcome upon its discontinuation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains limited.
Objective: To evaluate the outcomes following IST discontinuation in MOGAD.
Methods: This multicenter retrospective study collected data from 333 MOGAD patients in Korea. Among 273 patients who received IST, 41 who discontinued IST were analyzed.
Results: The median age at disease onset was 38.3 years (interquartile range (IQR), 27.6-53.1). Before IST withdrawal, 21 (51%) patients exhibited relapsing courses. Over a median follow-up of 23.5 months (IQR, 12.1-39.5) after discontinuation, 10 patients (24.4%) relapsed after a median of 8.2 months (IQR, 6.3-11.5). All relapses occurred in patients with a prior relapsing course (10/21, 47.6%); none with prior monophasic courses relapsed. Among 21 prior relapsing patients, relapse after discontinuation group had a shorter IST duration than non-relapse group (median, 9.4 vs 50.9 months, p = 0.036). None of the 41 patients had severe disability (Expanded Disability Status Scale (EDSS) score ⩾ 4.0 or Visual Functional System score ⩾ 5) at the last visit.
Conclusion: IST discontinuation did not necessarily lead to relapse and could be considered with an individualized approach based on factors such as disease course and IST duration.
Yeh WZ, Francis A, Cooper S, Rashid W, Martin R, Hobart J, Halfpenny C, Williams V, O'Sullivan E, Hemingway C, Hacohen Y, Dobson R, Waters P, Sharma SM, Butzkueven H, Geraldes R, Ramdas S, Leite MI, Palace J. Optimal strategies for treatment discontinuation in MOG antibody-associated disease. Brain. 2026 Feb 4:awag006. doi: 10.1093/brain/awag006. Epub ahead of print. PMID: 41637110.
Abstract
It is not known what the relapse risk is after immunomodulatory treatment discontinuation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Evidence suggests "at least" 3 months of oral corticosteroids reduces the 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 is unknown. We therefore aimed to investigate relapse outcomes following maintenance treatment discontinuation. 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, at least 12 months follow-up, and who commenced and then discontinued maintenance treatment were included. Associations of factors including treatment duration prior to discontinuation, disease course at discontinuation (after a single attack/monophasic or relapsing course) and MOG IgG1 status on live cell-based assay were investigated. Primary outcome was time-to-relapse following treatment discontinuation. Cox regression was used. We included 190 MOGAD patients with 236 discontinued treatment intervals. 150 (63.6%) discontinuations were after a single attack and before a first relapse when disease course was monophasic, and 86 (36.4%) discontinuations occurred in patients who had a relapsing disease course. Most patients used corticosteroids alone (84.7% IT intervals), and non-steroid IT 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 time of discontinuation (50% vs 27.8%, P=0.001) and a positive/low positive pre-discontinuation MOG IgG1 result (89.8% vs 71.5%, P=0.005). In multivariable analysis, a relapsing course at 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 durations prior to discontinuation beyond 3 months significantly reduced relapse risk. Optimal treatment durations were estimated as at least 10-18 months for patients treated after their onset attack and 20-30 months for relapsing patients, following 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.
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