Objective:

Since 2019, four biologic therapies have been approved to prevent relapses in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) and aquaporin-4 antibodies (AQP4-IgG+): eculizumab, inebilizumab, ravulizumab, and satralizumab (A-BIOs). It is unclear how these newer therapies are utilized in real-world practice.

Background:

NMOSD is a rare autoimmune disorder of the Central Nervous System that affects the optic nerves and spinal cord, leading to permanent disability and reduced quality of life. 

Design/Methods:

Patients with NMOSD from the US-based SPHERES (Synergy of Prospective Health & Experimental Research for Emerging Solutions) Registry enrolled from 6/2/2021 to 2/28/2025 were included (adults age ≥18 years diagnosed per 2015 IPND consensus diagnostic criteria). The study sequenced NMOSD therapies by tabulating all prior medication history reported up to the current therapy at the time of analysis. Demographics, lifestyle characteristics, comorbidities, NMOSD and clinical characteristics were summarized. 

Results:

Of 422 patients, 294 (70%) were AQP4-IgG+, 58 (14%) were myelin oligodendrocyte glycoprotein immunoglobulin G (MOG) seropositive, and 37 (9%) were seronegative. The mean age was 51 years, 84% were female, 58% were White, and 33% were Black/African American. Further, 200 (47%) required second- and 96 (23%) third-line therapy.

For monotherapies, rituximab (43%) was the most prescribed first-line therapy, followed by A-BIOs (21%) and IST (20%). Among the patients requiring second- or third-line monotherapy, A-BIOs were most prescribed (34% and 39%, respectively). Eculizumab and inebilizumab were the most common first-line A-BIOs; inebilizumab and satralizumab second-line; and satralizumab third-line.

Conclusions:

This study showed a predominant first-line rituximab use followed by A-BIOs; nearly half needed a second-line therapy or higher. We showed a preponderance of rituximab use in earlier lines of therapy, while A-BIOs, specifically inebilizumab, satralizumab, and eculizumab, were used more often as second or higher lines of therapy. Given accumulating disability with repeated attacks, these findings support earlier approved biologic use to prevent relapses.