Clinical phenotype and treatment response in AQP4-IgG-positive NMOSD and MOGAD: insights from the Italian I-MS&RD registry.

backgroundNeuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare entities distinct from multiple sclerosis. We leveraged the Italian Multiple Sclerosis and Related Disorders (I-MS&RD) Registry to characterise clinical and treatment features of AQP4-positive NMOSD and MOGAD, identify predictors of rituximab treatment response, and assess relapse outcomes across treatment classes.

methodsWe identified 664 patients from 97 Italian centres: 406 with AQP4+ NMOSD and 258 with MOGAD. Demographic, clinical, and treatment characteristics were compared between groups. Time to first relapse was assessed according to treatment class, comparing monoclonal antibodies with other therapies. Predictors of relapse-free status were evaluated using multivariable logistic regression.

resultsFemale sex was more common in AQP4+ NMOSD than in MOGAD patients (p < 0.001), whereas paediatric onset was more common in MOGAD (p < 0.001). Patients with AQP4+ NMOSD had greater disability at diagnosis than patients with MOGAD (p < 0.001). Rituximab was the most prescribed therapy. Treatment with monoclonal antibodies was associated with longer relapse-free survival in AQP4+ NMOSD (log-rank p = 0.021), but not in MOGAD. In AQP4+ NMOSD patients treated with rituximab, male sex and myelitis at onset were independently associated with a lower likelihood of remaining relapse-free (OR 0.37, 95% CI 0.14-0.94; p = 0.038 and OR 0.36, 95% CI 0.15-0.83; p = 0.017, respectively). In contrast, among rituximab-treated patients with MOGAD, optic neuritis at onset was the only predictor of relapse-free status at follow-up (OR 0.20, 95% CI 0.04-0.90; p = 0.038).

conclusionsThis nationwide, large-scale analysis, derived from the newly established I-MS&RD Registry, characterises a large Italian cohort of patients with AQP4+ NMOSD and MOGAD, identifies clinically relevant predictors of response to rituximab, and provides real-world evidence on treatment-associated relapse outcomes in these two disorders.