Switching therapy after rituximab resistance in AQP4-IgG+ NMOSD shows variable relapse outcomes.

Photo by Faustina Okeke / Unsplash

Frontiers in Medicine Published April 19, 2026 Medically reviewed April 25, 2026 Study authors: Meiqun Deng, Lei Chen, Wei Chen, Keyi Zeng, Yuxin Yao, Hanfei Chen, Aiyu Lin DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that inebilizumab, satralizumab, or eculizumab may be associated with lower relapse rates after rituximab resistance, but evidence is very limited.

This was a single-center, retrospective case series of 10 adults with AQP4-IgG+ NMOSD who exhibited disease activity despite sustained B cell depletion for more than six months post-rituximab (RTX resistance). The study evaluated switching therapy to ofatumumab, inebilizumab, satralizumab, or eculizumab, or de-escalation to mycophenolate mofetil, intravenous immunoglobulin, or steroids.

After a median follow-up of 28.4 months after the treatment switch, no relapses were observed among patients who received inebilizumab, satralizumab, or eculizumab. The single patient who switched to ofatumumab experienced a relapse. Among the four patients on de-escalation regimens, three (75%) had at least one relapse.

Regarding safety, no significant adverse events occurred in patients treated with ofatumumab, inebilizumab, satralizumab, or eculizumab. Two serious adverse events were reported among those on de-escalation regimens. The tolerability for inebilizumab, satralizumab, and eculizumab was favorable.

Key limitations include the small sample size (n=10), retrospective design, single-center setting, and descriptive case series nature with no direct comparator group. The practice relevance is that these real-world observations provide hypothesis-generating data, but causality cannot be established, and findings may not generalize beyond this specific population.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

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. 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). 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. 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.