Real-world experience with obinutuzumab in difficult-to-treat myositis: concise report of a case series

Objectives Idiopathic inflammatory myopathy (IIM) is an orphan systemic disorder with muscular, cutaneous and pulmonary involvement. B cell-directed therapies, including rituximab, belimumab, and CAR-T have shown promise in altering disease outcome. We report the benefit of obinutuzumab in refractory myositis patients with Methods Northwell Rheumatology database was searched for obinutuzumab treated patients (2019–2024); five of them met 2017 EULAR/ACR classification criteria for IIM and were included in the analysis. Demographic, clinical, serological, and imaging data were collected. Overall response was rated as complete, partial, or no response based on clinical response and physician global assessment. Total improvement score (TIS) was not calculated because data was collected retrospectively. Descriptive statistics were used for analyses. Results Of five patients, 2 had antisynthetase syndrome, 1 dermatomyositis, and 2 overlap myositis. Most patients failed at least 3 immunosuppressive agents. The reason for obinutuzumab use was rituximab allergy and worsening of interstitial lung disease (ILD) and myositis activity (3/5), arthritis (2/5), and severe rash (1/5 patients), despite rituximab. After obinutuzumab 80% of patients had overall improvement by 3-6 months. Respiratory status improved/stabilized in all ILD patients. Two patients required second obinutuzumab cycle: one for recurrence and another for persistent disease with B cell re-population. One was lost to follow-up after second cycle and was deemed a nonresponder. At last observation 4/5 patients achieved complete response. No hypogammaglobulinemia, significant infections, or hospitalizations were observed. Conclusion Obinutuzumab was safe and provided durable improvement in difficult-to-treat myositis patients with rituximab allergy, further highlighting targeting B-cell pathway.