Low-dose rituximab may be effective for patients with newly diagnosed generalized myasthenia gravis and may reduce the need for rescue therapies.

Little randomized trial evidence exists to support use of rituximab for myasthenia gravis (MG). In this trial, adults with non-thymomatous generalized MG, symptoms for <12 months, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more (out of 39 points, with higher scores representing more-severe disease) were randomized without stratification to a single infusion of rituximab 500 mg (n=25) or placebo (n=22). Patients taking prednisolone >40 mg daily or other steroid-sparing immunosuppressants were excluded. Only two participants did not have acetylcholine receptor (AChR) antibodies. There were baseline differences between the groups: Rituximab recipients were older than placebo recipients (mean, 67 years vs. 58 years), had lower AChR antibody titers (25.1 nmol/L vs. 70.7 nmol/L), and were less severely affected according to Myasthenia Gravis Foundation of America classification (MGFA), but were more likely to be on prednisolone (64% vs. 55%).

The primary endpoint, reaching minimal manifestation status (QMG score ≤4) and prednisolone dose ≤10 mg daily at 16 weeks, differed significantly between the rituximab and placebo groups (71% vs. 29%). A treatment benefit was also observed at 24, 36, and 48 weeks. Secondary endpoints did not differ, including AChR antibody titers at 24 weeks, although they trended toward favoring rituximab use. Fewer rituximab than placebo recipients required rescue treatments (4% vs. 36%) or were hospitalized (0 vs. 3 patients). A fatal cardiac event in a patient with preexisting heart disease occurred in the rituximab group.

Comment

The authors postulate that the benefit of rituximab treatment in early myasthenia gravis may be related to the reduction of long-lived plasma cells responsible for antibody secretion, although they considered other mechanisms given the lack of difference in acetylcholine receptor antibody titers after treatment. The role for rituximab among newer treatments and the ideal long-term dosing schedule remain uncertain, but this trial supports its use as an option for some newly diagnosed patients.