Subsequent treatment strategies following rituximab-resistance in AQP4-IgG+ neuromyelitis optica spectrum disorder: a case series.

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.