Rituximab Significantly Lessens Myasthenia Gravis Manifestations, Rescue Treatments Needed


Compared with placebo, a greater proportion of patients on rituximab met the primary end point of minimal disease manifestations at 16 weeks, and demonstrated favorable results on several secondary end points.

Miguel Chuquilin, MD

Miguel Chuquilin, MD

Data from the RINOMAX randomized clinical trial (NCT02950155) showed that a single dose of 500 mg of rituximab (Rituxan; Genentech), a medication traditionally used as a third-line option for refractory generalized myasthenia gravis (MG), was associated with a greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo.1

The primary outcome, minimal disease manifestations at week 16 defined as a Quantitative Myasthenia Gravis (QMG) score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment, was achieved by 71% (17 of 24) in the rituximab group vs 29% (6 of 21) on placebo (probability ratio, 2.48; 95% CI, 1.20-5.11; Fisher P = .007). The proportions fulfilling the same criteria at week 24 (tertiary end points) and weeks 36 and 48 similarly favored active treatment over placebo.

In a related editorial, Miguel Chuquilin, MD, and Richard Barohn, MD, wrote, "The reason for a better clinical response in patients with new-onset AChR gMG may be related to the reduction of formation of long-lived plasma cells responsible for antibody secretion. This is important because rituximab does not target plasmablasts or plasma cells (they are CD20 negative) but instead targets their precursors. However, in the current study, there was only a nonsignificant trend to reduced AChR antibody titers after rituximab treatment. Other mechanisms, such as modulation of cytokine production or elimination of CD20+ T and antigen-specific memory B cells, can also be considered."2

Led by Fredrik Piehl, MD, PhD, Department of Neurology, Karolinska University Hospital, the double-blind study featured patients older than 18 years, had onset of generalized symptoms within 12 months or less, and had a QMG score of 6 or more. Rituximab, a chimeric anti-CD20 monoclonal antibody approved for B-cell lymphoma, rheumatoid arthritis, and vasculitis, was administered as a single intravenous infusion at baseline, with 1000 mg of paracetamol, 10 mg of cetirizine, and 50 mg of prednisolone administered as premedication. Use of acetylcholine receptor (AChR+) antibodies as a symptomatic treatment was unrestricted, but doses were recorded at each visit.

In sensitivity analyses that fitted 2 logistic regression models—crude and adjusted for age, early-onset disease, and Myasthenia Gravis Foundation of America classification—the crude odds ratio was 6.07 (95% CI, 1.67-22.1), and significance remained after adjustment (OR, 4.63; 95% CI, 1.08-19.8). A post-hoc analysis excluding patients younger than 40 years with comorbidity, but results remained unchanged. Additionally, prednisolone doses at baseline did not appear to predict the primary end point.

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The 3 secondary outcomes, change in QMG score at 24 weeks, change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at 16 weeks, and change in Myasthenia Gravis Quality of Life (MG-Qol) score at 16 weeks, did not differ between treatment arms. In a post-hoc analysis using work rank imputations for those receiving rescue treatment, change in QMG score between baseline and week 24 and change in MG-ADL score at week 16 favored rituximab over placebo, with a trend also for MG-Qol score at week 16.

Rescue medication use, a tertiary end points, was less frequent in the rituximab group (1 of 25; 4%) than in those on placebo (8 of 22; 36%; P = .008). When displayed as a Kaplan-Meier curve, rescue events occurred more frequently in the placebo arm from week 9 until week 24. In terms of safety, there were a greater number of adverse events (AEs) found in the rituximab group than placebo (81 vs 44). Notably, 1 patient with MG with preexisting, but evaluated as stable, ischemic heart disease experienced a fatal cardiac event 4 weeks after baseline. Mild infusion reactions were also reported for 3 individuals on rituximab and 1 on placebo.

"This study provides evidence that low-dose rituximab may be effective in some patients with generalized AChR gMG, especially if started early after diagnosis," Chuquilin and Barohn added.2 “With the emergence of 2 new FDA-approved drug classes, we have entered a new MG treatment era. Nevertheless, older and repurposed drugs like rituximab may still have a role in MG treatment."

1. Piehl F, Eriksson-Dufva A, Budzianowska A, et al. Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: the RINOMAX randomized clinical trial. JAMA Neurol. 2022;79(11):1105-1112. doi:10.1001/jamaneurol.2022.2887
2. Chuquilin M, Barohn R. Rituximab in newly diagnosed generalized myasthenia gravis: a new treatment paradigm? JAMA Neurol. 2022;79(11):1100-1102. doi:10.1001/jamaneurol.2022.2311
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