ArticleFrontiers in immunology2026
Subsequent treatment strategies following rituximab-resistance in AQP4-IgG+ neuromyelitis optica spectrum disorder: a case series.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: This case series describes alternative treatments for adults with aquaporin 4 immunoglobulin G-seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) who exhibited disease activity despite having sustained B cell depletion for more than six months post-rituximab (RTX), a condition we defined as RTX resistance. Methods: We conducted a single-center, retrospective case series of 10 AQP4-IgG-positive NMOSD patients who met our definition of RTX resistance and subsequently switched therapies. Among the 10 patients, one was switched to the anti-CD20 monoclonal antibody ofatumumab, two to the anti-CD19 monoclonal antibody inebilizumab, two to the IL-6 receptor antagonist satralizumab, and one to the C5 complement inhibitor eculizumab, while 4 transitioned to de-escalations (mycophenolate mofetil, intravenous immunoglobulin, or steroids). Results: Over a median follow-up of 28.4 months after treatment switch, no relapses were observed among patients who received inebilizumab, satralizumab, or eculizumab. In contrast, the patient who switched to ofatumumab experienced relapse, and three of the four patients (75%) on de-escalations had at least one relapse. No significant adverse events occurred in patients treated with ofatumumab, inebilizumab, satralizumab, or eculizumab, while two serious adverse events were reported among those on de-escalation regimens. Conclusion: In this descriptive case series of 10 patients with RTX-resistant NMOSD, those who switched to inebilizumab, satralizumab, or eculizumab appeared to have fewer relapses and a favorable safety profile compared to those receiving de-escalation strategies or ofatumumab. These real-world observations provide hypothesis-generating data that may inform clinical decision-making and warrant validation in larger, prospective cohorts.
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