MOG DISCONTINUATION
(2026)Objective
To investigate relapse outcomes following maintenance immunomodulatory treatment (IT) discontinuation in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and identify predictors of post-discontinuation relapse.
Study Summary
• Relapsing course at time of discontinuation independently doubled relapse risk (adjusted HR 1.95, 95% CI 1.25-3.06, P=0.003)
• Treatment durations beyond 3 months significantly reduced relapse risk; optimal duration estimated at 10-18 months for monophasic patients and 20-30 months for relapsing patients
• 5-year relapse-free survival: 87.7% with 15-month IT vs 47.9% with 3-month IT in monophasic patients; 62.1% with 24-month IT vs 24.3% with 3-month IT in relapsing patients
• Positive/low-positive pre-discontinuation MOG IgG1 was more common in relapsers (89.8% vs 71.5%, P=0.005)
Intervention
Discontinuation of maintenance immunomodulatory treatment (oral corticosteroids, azathioprine, mycophenolate, methotrexate, IVIG, or monoclonal antibodies) after variable durations, analyzed by disease course at discontinuation.
Inclusion Criteria
Patients fulfilling 2023 MOGAD criteria seen at Oxford NMO Highly Specialised Service (Jan 2010 - May 2025); ≥12 months follow-up; commenced and discontinued eligible maintenance IT; consented to Demyelinating Research Tissue Bank.
Study Design
Arms: Monophasic course at discontinuation (n=150 intervals) vs Relapsing course at discontinuation (n=86 intervals)
Patients per Arm: 190 patients contributing 236 discontinued IT intervals (150 monophasic, 86 relapsing)
Outcome
• Relapsing course at discontinuation: adjusted HR 1.95 (95% CI 1.25-3.06, P=0.003)
• Longer IT duration associated with reduced relapse hazard (nonlinear)
• Negative MOG IgG1 (sensitivity analysis within 12 months of discontinuation): HR 0.38 (95% CI 0.15-0.99)
• Timing of onset attack acute treatment did not affect relapse risk
• Optimal IT duration: 10-18 months (monophasic); 20-30 months (relapsing)
Bottom Line
In MOGAD, prolonged maintenance IT beyond 3 months significantly reduces post-discontinuation relapse risk. Treatment durations of 10-18 months (after a single/monophasic attack) and 20-30 months (in relapsing disease) balance relapse reduction against IT-related risks; relapsing disease course at discontinuation nearly doubles relapse risk (HR 1.95).
Major Points
- Largest cohort study to date of MOGAD IT discontinuation: 190 patients, 236 discontinued IT intervals from Oxford NMO Highly Specialised Service (2010-2025).
- 39% of discontinuations were followed by relapse at median 5.4 months.
- Relapsing disease course at time of IT discontinuation independently doubled relapse risk (adjusted HR 1.95, 95% CI 1.25-3.06, P=0.003).
- Longer IT duration prior to discontinuation was significantly protective; effect plateaued at 10-15 months (monophasic) and ~20 months (relapsing).
- Estimated optimal treatment duration: 10-18 months for monophasic patients, 20-30 months for relapsing patients.
- 5-year relapse-free survival for monophasic patients: 87.7% (15-mo IT) vs 47.9% (3-mo IT).
- 5-year relapse-free survival for relapsing patients: 62.1% (24-mo IT) vs 24.3% (3-mo IT).
- Negative pre-discontinuation MOG IgG1 was associated with lower relapse hazard in sensitivity analysis (HR 0.38, 95% CI 0.15-0.99).
- Timing of onset attack acute treatment (early/intermediate/late) did NOT affect subsequent relapse risk after discontinuation.
- Cohort was predominantly steroid-treated (84.7% used corticosteroids alone).
Study Design
- Study Type
- Retrospective single-service cohort study with prospective data collection
- Randomization
- No
- Blinding
- None (observational)
- Sample Size
- 190
- Follow-up
- Median disease duration 4.9 years (IQR 2.5-8.2) at last follow-up; minimum 12 months follow-up required
- Centers
- 1
- Countries
- United Kingdom
Primary Outcome
Definition: Time-to-relapse (new clinical attack >30 days after prior attack) following IT discontinuation
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Monophasic at discontinuation: 27.8% relapsed | Relapsing at discontinuation: 50% relapsed | 1.95 (1.25-3.06) | 0.003 |
Limitations & Criticisms
- Single-center, retrospective observational design susceptible to selection and referral bias.
- Cohort predominantly treated with corticosteroids (84.7%); limited data on steroid-sparing agents and monoclonal antibodies.
- Missing pre-discontinuation MOG IgG1 status in 16.9% of intervals required multiple imputation.
- Optimal duration estimates depend on modeling assumptions (restricted cubic splines with 3 knots) and reference to 3-month cutpoint.
- Some patients contributed multiple discontinuation intervals (up to 3), addressed by clustered robust standard errors but still a potential source of within-patient correlation.
- IT duration and time from last attack to discontinuation were highly correlated (r=0.87), limiting separation of their effects.
- Wide confidence intervals for long-duration survival estimates (e.g., 5-year monophasic 15-mo IT CI up to 100%) reflect diminishing precision.
- Discrepancy in sensitivity multivariable P-value (0.49 reported) versus HR (0.38, 95% CI 0.15-0.99) suggests possible typographical error in source.
Citation
Yeh WZ, et al. Optimal strategies for treatment discontinuation in MOG antibody-associated disease. Brain. 2026. doi:10.1093/brain/awag006