A novel limited-dose C5 inhibitor add-on as rescue therapy for refractory NMOSD attacks: a practical alternative to conventional multi-dose regimens

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) patients with refractory attacks, despite standard therapy with high-dose intravenous methylprednisolone (IVMP) and plasma exchange (PLEX), often experience significant disability. While complement C5 inhibition has established efficacy in relapse prevention, its role in acute-phase management remains unclear. METHODS: In this single-center, retrospective case series, eight patients (6 AQP4-IgG seropositive, 2 seronegative) with acute NMOSD and suboptimal responses to IVMP ± PLEX were treated with 1-4 weekly doses of ECU (900 mg per dose). The primary outcome was the change in functional scores (EDSS for myelitis and logMAR visual acuity (VA) of the worse eye for optic neuritis) from pre-ECU baseline to 1 and 3 months post-ECU. The secondary outcomes included the proportion of patients achieving good improvement, and safety. RESULTS: Six patients presented with severe, refractory attacks (median nadir EDSS/VA: 9.0/2.5) showing minimal response to conventional therapy (median post-IVMP/PLEX EDSS/VA: 8.75/2.5). The remaining two patients, while not meeting the criteria for a severe attack, also had an unsatisfactory response to first-line treatment. Add-on limited-dose ECU enhanced neurological function. In myelitis patients, the median EDSS score improved from 8.5 at baseline to 3.5 at 3 months. In optic neuritis patients, the median VA score improved from 1.9 to 0.5. The proportion of patients achieving good response increased from 42.9% at 1 month to 100% at 3 months. Both seronegative patients also responded favorably. The treatment regimen was well-tolerated, with no serious adverse events other than anti-HBc seroconversion in one patient, highlighting the importance of infectious monitoring during complement inhibition. CONCLUSIONS: Limited-dose ECU appears to be an effective rescue therapy for accelerating recovery in refractory NMOSD attacks, including in seronegative patients, with a generally favorable safety profile. It represents a promising bridging strategy to long-term immunosuppression, addressing a critical unmet need in acute-phase NMOSD management.