Treatment Discontinuation in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Overview

Myelin oligodendrocyte glycoprotein antibody-associated disease, or MOGAD, is an autoimmune inflammatory disorder of the central nervous system. In this condition, the immune system mistakenly attacks myelin oligodendrocyte glycoprotein, a protein found on the surface of myelin in the brain, optic nerves, and spinal cord. This can lead to attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or other demyelinating events. Many patients recover well after an attack, but some experience relapses, which is why long-term treatment is often considered.

This study examined an important and practical question: what happens when maintenance treatment is stopped in adults with MOGAD? As newer strategies increasingly aim to reduce long-term exposure to immunosuppressive therapy, clinicians need evidence to balance relapse prevention against medication risks such as infection, liver toxicity, cytopenias, infusion reactions, and other adverse effects.

Why treatment discontinuation matters in MOGAD

Maintenance therapies for MOGAD are usually intended to reduce the risk of future inflammatory attacks. Common options include oral immunosuppressants such as azathioprine and mycophenolate mofetil, as well as B-cell depleting therapy such as rituximab. These agents can help prevent relapses, but they are not free of harm. Some patients develop side effects, while others improve clinically and wish to stop treatment after a period of stability.

In routine practice, discontinuation may occur for two broad reasons. First, treatment may be planned and scheduled because the patient appears stable or because both patient and clinician want to reassess the need for ongoing therapy. Second, treatment may be stopped because of adverse events, intolerance, or safety concerns. Understanding the relapse risk after stopping therapy in both situations is especially useful because not all patients have the same baseline risk.

Study design and population

This retrospective cohort study used the French NOMADMUS database and included adults diagnosed with MOGAD between January 2013 and April 2024. The study involved 41 centers across France, making it one of the larger real-world datasets on this topic.

Among 1,047 screened patients, 705 met the inclusion criteria. Of these, 319 patients, or 45.2%, had received at least one maintenance therapy. The analysis focused on 83 patients who discontinued treatment in a documented and analyzable way. Their median age was 42.7 years, and 63.7% were female.

The therapies stopped were mostly oral immunosuppressants such as azathioprine or mycophenolate mofetil in 60 patients, and rituximab in 23 patients. Discontinuation was planned in 54 patients and related to adverse events in 29 patients.

Main findings

After treatment discontinuation, 7 of the 83 patients experienced a relapse. The median time to relapse was 0.5 years, which means that when relapse occurred, it tended to happen relatively soon after treatment was stopped. However, the overall relapse risk remained low.

Using Kaplan-Meier analysis, the estimated cumulative incidence of relapse at 1 year after stopping treatment was 8.7%, with a 95% confidence interval of 1.0% to 15.9%. In practical terms, this suggests that most patients in this selected cohort did not relapse within the first year after treatment discontinuation.

The relapses that did occur were generally mild. The median change in Expanded Disability Status Scale, or EDSS, was 0 points, with an interquartile range of 0 to 1. This implies that most relapses did not lead to major persistent disability in this group, although any relapse can still be clinically significant, particularly when vision, strength, or mobility is affected.

Who seemed to be at higher risk?

Two factors were associated with a higher relapse risk after treatment discontinuation.

First, treatment duration of less than 1 year was linked to more relapses. In this subgroup, 7 relapses occurred among 19.4% of patients, compared with none in patients treated for a longer period. The difference was statistically significant.

Second, the time since the last relapse was important. Patients who stopped treatment when their last relapse had occurred less than 2 years earlier had a higher risk of disease reactivation. Again, 7 relapses occurred in this group, whereas no relapses were observed in those with a longer relapse-free interval.

These findings suggest that stopping maintenance therapy may be safer in patients who have had a prolonged stable period and a longer interval since their last attack. In contrast, patients who are early in their disease course or who recently relapsed may still benefit from continued treatment.

How to interpret the results

This study does not mean that treatment should be stopped broadly in all patients with MOGAD. Rather, it suggests that carefully selected adults may be able to discontinue therapy with a relatively low short-term risk of relapse.

The results are encouraging because they support a more individualized approach. For some patients, prolonged immunosuppression may not be necessary if they have remained stable for a long period, especially if they are experiencing drug toxicity, recurrent infections, or other burdens from therapy. For others, especially those with more active disease, stopping treatment too early may increase relapse risk.

The finding that relapses were often mild is also reassuring, but it should be interpreted cautiously. A mild average relapse does not eliminate the possibility of a severe attack in an individual patient. For example, even a single optic neuritis relapse can have meaningful consequences for vision and quality of life.

Clinical context: MOGAD treatment is not one-size-fits-all

MOGAD is increasingly recognized as distinct from multiple sclerosis and from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Its course can be monophasic in some patients and relapsing in others. Because the disease spectrum is broad, treatment decisions need to reflect individual relapse history, disease severity, age, disability burden, antibody status, and patient preferences.

Common maintenance strategies include azathioprine, mycophenolate mofetil, rituximab, and in some settings other immunotherapies such as intravenous immunoglobulin. Each option has a different safety profile and monitoring burden. The decision to stop therapy is often not simply a question of whether the drug is working, but whether the risks of continued treatment outweigh the likely benefit at a given point in the disease course.

This study adds useful real-world evidence to that decision-making process. It suggests that, at least in adults who have been stable for a meaningful period, discontinuation can be considered rather than assumed to be unsafe.

Important limitations

As with any retrospective study, there are important limitations. Treatment discontinuation was not randomized, so the patients who stopped therapy were likely different from those who continued treatment. Clinicians may have been more willing to stop therapy in patients they believed were at lower risk, which can make the results look more favorable than they might in an unselected population.

The number of relapses after discontinuation was small, which is helpful for understanding the overall event rate but limits the precision of risk estimates and subgroup analyses. The study also focused on adults, so the findings may not apply to children or adolescents with MOGAD.

In addition, the analysis did not establish a universal rule for when treatment should be stopped. Instead, it identified associations that may help guide clinical judgment. Prospective studies and, ideally, clinical trials are still needed to determine the safest discontinuation strategy, the best timing for stopping treatment, and which biomarkers or clinical features might predict relapse more reliably.

Practical takeaways for patients and clinicians

For patients with MOGAD, this study offers a cautiously optimistic message. If a person has been stable for a long time, especially with a long interval since the last relapse and more than a year of maintenance therapy, stopping treatment may be reasonable to discuss with a neurologist experienced in autoimmune demyelinating disease.

For clinicians, the study supports shared decision-making rather than routine indefinite treatment. Before stopping therapy, it may be helpful to review the following factors: number of prior attacks, severity of previous relapses, duration of disease stability, time since last relapse, prior treatment response, side effects, infection risk, and the patient’s ability to access urgent care if symptoms recur.

If treatment is discontinued, close follow-up remains important, particularly during the first year, when relapse risk may be highest. Patients should be educated about early warning symptoms such as new visual loss, eye pain, limb weakness, numbness, bladder dysfunction, or gait difficulty, and advised to seek prompt medical evaluation if these occur.

Conclusion

In this multicenter French cohort, stopping maintenance therapy in selected adults with MOGAD was associated with a relatively low short-term relapse risk. Only 8.7% of patients relapsed within 1 year after discontinuation, and most relapses were mild. Higher risk was seen when treatment had been used for less than 1 year or when the last relapse had occurred less than 2 years earlier.

Overall, the study suggests that treatment discontinuation may be a reasonable option for carefully selected adult patients with stable MOGAD. However, the decision should remain individualized, and larger prospective studies are needed before firm guidelines can be established.