Complement Inhibition May Stabilize AQP4-Positive NMOSD After Inebilizumab Failure, Analysis Suggests

A new analysis showed that complement inhibition with eculizumab (Soliris; Alexion) or ravulizumab (Ultomiris; Alexion) was associated with clinical stabilization among Hispanic patients with aquaporin-4–positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) who experienced breakthrough disease when receiving inebilizumab (Uplinza; Amgen). These findings were recently presented at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 27-29, Charlotte, North Carolina.¹

Coming into the study, a small cohort of 7 patients experienced at least 1 MRI-confirmed relapse when treated with inebilizumab, with transverse myelitis and optic neuritis reported most frequently. Presented by coauthor R. Alejandro Cruz, MD, neuroimmunologist and co-chairman of Neuroscience at the DHR Health Multiple Sclerosis Center in Texas, and colleagues, 6 of these participants had documented B-cell depletion at the time of relapse, suggesting biologic treatment failure rather than nonadherence.

Although B-cell depletion with inebilizumab is an approved treatment approach for AQP4+ NMOSD,² some patients continue to experience relapses despite complete B-cell suppression.

This retrospective single-center cohort analysis identified patients with AQP4-positive NMOSD who experienced relapses or progressive disability while receiving inebilizumab between 2020 and 2025 and were later transitioned to complement inhibition therapy with eculizumab or ravulizumab. Treatment failure was defined by the development of new enhancing MRI lesions, clinical relapse requiring acute treatment, or sustained worsening on the EDSS despite treatment adherence and/or confirmed B-cell depletion.

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Overall, the median Expanded Disability Status Scale (EDSS) score at the time of transition to complement inhibition was 7.0 (range, 6.0-8.5). Following initiation of complement inhibition, all treated patients achieved clinical stabilization in 2 to 4 weeks. However, disability present before rescue treatment, including paraplegia and vision loss, remained irreversible during the short follow-up period. Notably, no severe adverse events associated with complement blockade were reported.

Investigators concluded that complement inhibition may represent a potential rescue strategy for patients with AQP4-positive NMOSD who experience relapse on inebilizumab despite confirmed B-cell suppression. All patients in the study were B-cell depleted at the time complement inhibition was initiated and subsequently received meningococcal vaccination along with prophylactic antibiotics for 2 months until booster immunization was completed to reduce infection risk.

Moreover, authors noted that earlier identification of breakthrough disease and timely transition to complement blockade may help limit additional irreversible disability. In addition, researchers acknowledged that the study was limited by its short mean follow-up duration of 10 months, noting that longer-term observation is needed to determine whether clinical stabilization is sustained.

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REFERENCES
1. Salinas DI, Cruz RA, Rodriguez MM. Complement Inhibition as Rescue Therapy After Inebilizumab Failure in Hispanic Patients With Neuromyelitis Optica Spectrum Disorder: A Single-Center Retrospective Analysis. Presented at: 2026 CMSC Annual Meeting; May 27-29; Charlotte, North Carolina. Abstract RTH01.
2. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. News release. FDA. June 11, 2020. Accessed May 27, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-rare-disease-affecting-optic-nerve-spinal-cord