Background and ObjectivesTo evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized antiâinterleukin-6 receptor antibody in myelin oligodendrocyte glycoproteinâIgGâassociated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).MethodsAnnualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.ResultsPatients received TCZ for 23.8 months (median; interquartile range 13.0â51.1 months), with an IV dose of 8.0 mg/kg (median; range 6â12 mg/kg) every 31.6 days (mean; range 26â44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5â5) to 0 (range 0â0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0â5] to 0 [range 0â4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0â3.0] to 0.2 [range 0â2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.DiscussionThis study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.