Anti-IL6R Therapy Effective in Reducing NMOSD and MOGAD Disease Activity

A study recently published in Sage Journals found that anti-interleukin-6 receptor (anti-IL6R) therapy was effective in reducing disease activity in both neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), particularly in patients previously unresponsive to rituximab.¹

In the main findings, senior author Nicolas Collongues, MD, PhD, professor and neurologist at Strasbourg University Hospitals in France, and his colleagues observed that anti-IL6R therapy was associated with a significant reduction in annualized relapse rates among treated patients. Relapse rates during anti-IL6R exposure were significantly lower than during the 1-year pre-exposure period in both AQP4-positive NMOSD (n = 25, P = 0.007) and MOGAD (n = 15, P = 0.003), with no significant change observed in Expanded Disability Status Scale (EDSS) scores.

Among the 51 participants included, anti-IL6R therapy was used as a second-line treatment in just over half of cases (51%), and 62.7% of previously received rituximab. Despite higher cerebrospinal fluid (CSF) IL-6 levels in patients with MOGAD, no correlation was found between CSF IL-6 concentrations and relapse rates.

“We sought to determine whether IL6 in the CSF could be a predictive factor of anti-IL6R response,” said study authors.¹ “The IL6 levels collected from the French centers were all measured before the introduction of a first immunosuppressive treatment, which means that lumbar puncture was usually performed only at diagnosis and was not part of the patients’ medical follow-up. We were unable to demonstrate the prognostic role of IL6 levels in CSF on recovery after a relapse.”¹

The study included patients from the NOMADMUS registry with NMOSD or MOGAD who had received at least one dose of anti-IL6R therapy. Relapse incidence and timing were analyzed in relation to treatment exposure periods, and survival and correlation analyses were conducted to assess associations between CSF IL-6 levels and relapse occurrence.

The authors noted several study limitations that may restrict how firmly conclusions could be drawn. Potential selection bias was present, as all participants received anti–IL6R therapy during follow-up, and longer follow-up periods may have limited exposure to satralizumab given its European approval in 2021. Additionally, incomplete data and the absence of CD19⁺/CD20⁺ B-cell measurements before anti–IL6R initiation limited interpretation, particularly among patients previously treated with rituximab. Furthermore, analyses of CSF IL-6 were further constrained by a small number of samples, variable assay methods, and inconsistent timing between IL-6 measurement and treatment initiation.

“This study contributes to IL6 research by providing new evidence that anti-IL6R therapy was associated with a reduction in disease activity in both NMOSD and MOGAD,” the study authors noted.¹ “A more systematic and standardized assay of IL6 in CSF could lead to a better understanding of the distinct pathophysiology of these two diseases and provide new keys to guide clinicians with achieving more personalized prescriptions.”¹

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In previous studies, CSF IL-6 has been tested as predictive biomarker for autoimmune disorders like NMOSD and MOGAD. A 2025 study published in BMC Neurology investigated the association between CSF IL-6 levels, progressive disease, and disease severity in multiple sclerosis (MS), a similarly related autoimmune disorder. In the trial, patients with progressive MS displayed elevated IL-6 levels in the CSF, and CSF IL-6 showed positive correlations with EDSS scores, the Multiple Sclerosis Severity Score, and CSF glial fibrillary acidic protein levels.²

Further investigation concluded that IL-6 in CSF indicates ongoing CNS inflammation and may contribute to the compartmentalized inflammation associated with disease progression and overall disease severity. This was found through the use of advanced technologies, including single-molecule arrays and microfluidics that analyzed CSF samples from individuals with MS at the time of diagnosis for IL-6. IL-6 levels were then correlated with clinical course, disease severity, and other known biomarkers associated with inflammation and disease severity.

REFERENCES
1. Comet C, Jouvenot G, Bourre B, et al. Place of anti-IL6R in the therapeutic strategy in NMOSD-AQP4+, MOGAD, and NMOSD double-seronegative patients. Mult Scler. Published online December 17, 2025. doi:10.1177/13524585251396421
2. Itorralba, J., Brand-Arzamendi, K., Saab, G. et al. Intrathecal interleukin-6 levels are associated with progressive disease and clinical severity in multiple sclerosis. BMC Neurol 2025;25(136). Doi: 10.1186/s12883-025-04145-0