Efficacy and safety of different dosages of rituximab for myasthenia gravis: a single-arm meta-analysis.

Abstract

Background: Rituximab (RTX) is one of the treatment options for refractory myasthenia gravis (MG), yet the optimal dosing schedule remains undetermined. Our study aims to explore this issue and offer a valuable reference for clinical dosing.

Methods: This is a single-arm meta-analysis. Studies in adults with myasthenia gravis published before 31 December 2023 were searched in PubMed, Web of Science, and other databases. Two primary effectiveness outcomes were analyzed: (1) Proportion of patients achieving minimal manifestation status (MMS) or better, (2) Change in Quantitative MG Score (QMGs) after RTX treatment. Safety outcomes included the incidence and description of serious adverse events (SAEs) and adverse events (AEs). Forest plots were generated to provide an overview and detailed combined effects. Publication bias was evaluated using funnel plots and the Egger test. Conventional dose refers to an RTX regimen similar to that used for the treatment of B-cell lymphoma: 375 mg/m² per week for 4 weeks or 1000 mg for Weeks 1 and 3. Dosing regimens below the conventional dose in a treatment cycle are defined as low dose.

Results: A total of 1037 MG patients received RTX treatment. Overall, 59.0% (95% CI: 48.2-69.8%, n = 599) of patients achieved MMS or better, with a mean decrease in QMGs of 6.81 (95% CI, -9.27 to -4.35, n = 222). The low-dose group showed a higher proportion of patients achieving MMS or better (76.6% vs 51.6%) and a more significant decrease in QMGs from baseline (-9.04 vs -3.62) compared to the conventional dose group (P < 0.01). Differences in the incidence of SAEs and AEs between the two groups were not significant (P > 0.05). Univariate meta-regression analyses showed that the dose administered was significantly associated with the proportion of MMS or better and the change in QMGs, whereas the proportion of Musk patients was not significantly associated with any of the outcomes. Stepwise logistic regression analyses showed that non-refractory MG, mild disease severity (MGFA classification), and low-dose were significant predictors for achieving an MMS or better prognosis, whereas for achieving improvement or better, only low dose was an independent predictor.

Conclusion: RTX can improve clinical symptoms, reduce QMGs in MG patients and the use of oral glucocorticoids and other immunosuppressants. The efficacy of low-dose RTX in treating MG patients is more effective than conventional-dose RTX and demonstrates a better safety profile. Mild disease severity, non-refractory MG, low dose, and MuSK-MG over AChR-MG predict better efficacy. Large randomized controlled trials are necessary to evaluate the efficacy and safety of RTX in MG patients and its various subtypes.