Anti-IL6R Therapy Cuts NMOSD & MOGAD Activity

A new study published in Sage Journals offers a promising signal for patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) who haven’t responded to first-line treatments. Researchers have found that anti-interleukin-6 receptor (anti-IL6R) therapy significantly reduces disease activity in these challenging-to-treat autoimmune conditions, potentially offering a crucial alternative for those failing rituximab. This finding is particularly important as the search for effective and targeted therapies for NMOSD and MOGAD continues to intensify, driven by a growing understanding of the distinct immunological mechanisms at play in these disorders.

NMOSD and MOGAD are rare, debilitating autoimmune diseases affecting the central nervous system. Unlike multiple sclerosis (MS), which primarily targets the brain and spinal cord, these disorders specifically attack the optic nerves and spinal cord, leading to vision loss, weakness, and sensory disturbances. Rituximab, a B-cell depleting therapy, has become a standard first-line treatment, but a significant proportion of patients don’t achieve sustained remission or experience breakthrough relapses. This is where anti-IL6R therapy steps in, targeting a different part of the inflammatory pathway. Interleukin-6 (IL-6) is a key cytokine – a signaling molecule – involved in inflammation, and blocking its receptor can dampen the immune response.

The study, led by Nicolas Collongues, MD, PhD, and colleagues at Strasbourg University Hospitals, analyzed data from the NOMADMUS registry, focusing on 51 patients who received anti-IL6R therapy. The observed reduction in relapse rates – statistically significant in both AQP4-positive NMOSD and MOGAD – is encouraging. However, the researchers rightly point out several limitations. The retrospective nature of the study introduces potential selection bias, and the limited follow-up period, particularly for satralizumab (approved in Europe in 2021), means long-term efficacy remains to be fully established. The lack of consistent CD19⁺/CD20⁺ B-cell measurements before initiating anti–IL6R therapy also complicates interpretation, especially in patients previously treated with rituximab.

The Forward Look

The findings from this study are likely to prompt a re-evaluation of treatment algorithms for NMOSD and MOGAD. While not a replacement for first-line therapies, anti-IL6R is establishing itself as a valuable second-line option, particularly for those who have failed rituximab. However, the negative correlation between CSF IL-6 levels and treatment response is a critical area for further investigation. The authors’ call for standardized IL-6 assays is well-placed. Future research should focus on identifying biomarkers that *can* predict response to anti-IL6R therapy, potentially allowing for a more personalized approach to treatment. Furthermore, ongoing clinical trials evaluating newer therapies, such as the neuroprotective agent Privosegtor (recently granted FDA Breakthrough Therapy Designation for optic neuritis – Neuroprotective Agent Privosegtor Gains FDA Breakthrough Designation for Optic Neuritis), will be crucial in expanding the therapeutic landscape for these devastating neurological conditions. The parallel research into IL-6’s role in multiple sclerosis, as highlighted by a 2025 BMC Neurology study, suggests a broader role for this cytokine in CNS autoimmune diseases, potentially opening avenues for shared therapeutic strategies.

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