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Background: The placebo-controlled RINOMAX trial (NCT02950155) demonstrated superiority up to 12 months of rituximab over standard-of-care in new-onset generalized myasthenia gravis (MG), but benefit–risk over longer time frames remains unknown.

Methods: RINOMAX included 47 participants with a Quantitative Myasthenia Gravis (QMG) score ≥ 6. Twenty-five patients were randomized to a single intravenous infusion of 500 mg rituximab, and 22 to placebo of which 16 received rituximab after the double-blinded phase (7 ± 2.9 months). Data were extracted from the Swedish MG registry to track hospitalizations, treatments including rescue, and disease activity scores.

Results: Compared to the placebo arm, lower mean time-weighted QMG scores at 12 months (mean difference [MD]: 2.9, 95% CI: 0.9, 4.9; p = 0.005) and 24 months (MD: 2.6, 95% CI: 0.3, 4.9; p = 0.027) were observed in the RTX arm. The incidence rate of rescue from 48 weeks up to 5 years was numerically higher in the placebo arm than RTX (0.16 vs. 0.09/person-year; p = 0.121). Compared to delayed RTX, early exposure displayed lower QMG, risk of hospitalization (HR 0.24, 95% CI 0.07, 0.83), and rescue (HR 0.46, 95% CI 0.14, 1.57), but also the six patients never receiving RTX showed lower hospitalization risk (HR 0.08, 95% CI 0.01, 0.96). Corticosteroid doses were low globally throughout. Overall, 12.5% and 18.8% and of patients with early and delayed RTX, respectively, suffered a severe infection.

Conclusion: Disease activity and treatment burden, including hospitalization and rescue treatments, remained low, indicating a potential benefit of rituximab on the long-term disease trajectory. Infection risk with B cell depletion, however, remains a concern.