Interleukin 6 Receptor Blockade: A Promising Strategy for Relapse Prevention in MOG Antibody-Associated Disease

Highlight

• IL-6 receptor blockers (IL-6RB), including tocilizumab and satralizumab, significantly reduce relapse rates in patients with relapsing MOG antibody-associated disease (MOGAD).
• The annualized relapse rate (ARR) decreased from 0.64 before IL-6RB treatment to 0.09 during therapy, demonstrating an 88% reduction in relapses.
• IL-6RB therapy showed comparable relapse prevention to high-dose intravenous immunoglobulin (IVIG ≥1 g/kg every 4 weeks) but was superior to lower IVIG dosing.
• Safety data indicated mostly mild infections, with severe infections occurring in 9% of patients, underscoring an overall favorable safety profile.

Study Background

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system characterized by relapses that can lead to neurological disability. Despite increasing recognition, there remain no fully approved or universally accepted relapse-prevention therapies for MOGAD. Treatment options, such as intravenous immunoglobulin (IVIG), corticosteroids, and other immunosuppressants, have variable efficacy, and some carry significant costs or adverse effects. Interleukin 6 (IL-6) is a proinflammatory cytokine implicated in autoimmune neuroinflammation, and blocking its receptor has shown promise in related conditions like neuromyelitis optica spectrum disorder (NMOSD). However, the evidence base on IL-6 receptor blockers (IL-6RB) in MOGAD has been limited by small cohorts and a lack of comparative effectiveness studies, restraining widespread clinical adoption.

Study Design

This international, multicenter, retrospective cohort study analyzed data from 116 patients with MOGAD treated with IL-6RB therapy (tocilizumab or satralizumab) between January 1, 2015, and December 31, 2025. The geographic scope included multiple centers across North and South America (United States, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). The study included all patients receiving at least one dose of IL-6RB with no exclusions.

As a comparator, a historical cohort of 59 patients treated with varying doses of IVIG was included to assess differential relapse outcomes. Key outcomes included the annualized relapse rate (ARR) during IL-6RB treatment, time to next relapse post-treatment initiation, and adverse events. Statistical adjustment using inverse probability of treatment weighting (IPTW) accounted for age, sex, prior relapse rate, and concomitant therapies to minimize confounding bias.

Key Findings

The cohort treated with IL-6RB consisted mainly of tocilizumab recipients (90%) and was predominantly female (60.3%) with 18% under 18 years of age. The median treatment duration was 1.4 years, accounting for 241.8 person-years of exposure. During IL-6RB therapy, the ARR dropped markedly from a pre-treatment 0.64 (95% CI, 0.58–0.70) to 0.09 (95% CI, 0.06–0.14), equating to an 88% relative reduction (incidence rate ratio 0.08; 95% CI, 0.04–0.16). Notably, 23 relapses occurred among all patients on IL-6RB during the study period.

In the IVIG cohort, 30 relapses occurred over 133.8 person-years, corresponding to an ARR of 0.22 (95% CI, 0.15–0.32). When stratified by dosing, IL-6RB treatment was associated with a significantly lower risk of relapse compared to IVIG doses less than 1 g/kg every four weeks (hazard ratio [HR], 4.5; 95% CI, 2.0–9.8). However, the difference was not statistically significant when compared with higher IVIG doses (≥1 g/kg every four weeks; HR, 2.0; 95% CI, 0.8–4.5), indicating comparable efficacy between IL-6RB and high-dose IVIG regimens.

Safety assessments revealed that 50% of patients on IL-6RB experienced adverse events, predominantly mild infections such as upper respiratory and urinary tract infections. Severe infections were reported in 9% of the cohort, highlighting a need for vigilance but suggesting an acceptable safety profile in this population.

Expert Commentary

The study provides compelling evidence supporting IL-6 receptor blockade as an effective relapse-prevention strategy in MOGAD. The dramatic reduction in relapse frequency is consistent with IL-6’s role in autoimmune neuroinflammation. Tocilizumab’s widespread availability and lower cost compared to other biologics or chronic IVIG infusions may enhance accessibility globally, particularly in resource-limited settings.

Limitations include the retrospective design, potential residual confounding, and a relatively modest follow-up duration. Moreover, head-to-head randomized trials are required to conclusively establish comparative efficacy and long-term safety. The occurrence of severe infections, though limited, warrants careful patient monitoring during IL-6RB therapy.

From a mechanistic perspective, IL-6RB likely modulates B-cell populations and downstream inflammatory cascades implicated in MOG antibody-mediated pathology, which complements the immunomodulatory effects of IVIG.

Conclusion

This large multinational retrospective study demonstrates that IL-6 receptor blockade with tocilizumab or satralizumab significantly reduces relapse rates in MOG antibody-associated disease with a favorable safety profile. Its relapse-preventive efficacy matches that of higher-dose IVIG therapy, suggesting it as a viable alternative or adjunct treatment. Given its accessibility and cost-effectiveness, IL-6RB holds promise for widespread clinical adoption in managing relapsing MOGAD. Prospective randomized controlled trials are warranted to validate these findings and optimize treatment protocols.

Funding and ClinicalTrials.gov

The study was conducted under the umbrella of The Americas MOGAD Treatment Group. Specific funding sources were not stated in the publication. ClinicalTrials.gov registration details were not provided.

References

Vilaseca A, Bilodeau PA, Gakis G, et al. Interleukin 6 Receptor Blockade for Relapse Prevention in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease. JAMA Neurology. 2026;PMID: 42440328.

Ramanan S, Tantsis E, Kenna PF, et al. Treatment of anti-MOG antibody-associated disease: a systematic review. J Neurol Neurosurg Psychiatry. 2020;91(2):125-134. doi:10.1136/jnnp-2019-321452

Reindl M, Di Pauli F, Rostasy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol. 2013;9(8):455-461.