Single dose of rituximab for new-onset myasthenia gravis associated with reduced risk of disease manifestations – The RINOMAX Randomized Clinical Trial

1. In this randomized clinical trial, among 47 individuals, the proportion with minimal myasthenia gravis (MG) manifestations with only low doses of corticosteroids and no need for rescue treatment at 4 months was 71% with rituximab, compared to 29% with placebo.

2. Rescue treatments were more frequent in the placebo group compared with the rituximab group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Myasthenia gravis (MG) is a neuroimmunological condition characterized by skeletal muscle weakness. Most patients with MG carry serum acetylcholine receptor antibodies, however, a proportion of patients lack antibodies to known antigenic targets. Based on current treatment guidelines, first-line therapy for MG consists of oral corticosteroids and biological treatments are typically considered third-line options. The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of rituximab compared with placebo as an addition to the standard care regimen for MG. The study took place over 48 weeks at 7 regional clinics across Sweden. Participants were randomized in a 1:1 ratio to receive a single intravenous infusion of 500 mg of rituximab or matching placebo. The primary endpoint was minimal disease manifestations at 16 weeks (Quantitative Myasthenia Gravis score [QMG] of 4 or less) with prednisolone, 10 mg or less daily, and no rescue treatment. A total of 87 eligible patients were randomized to rituximab (n=25), or placebo (n=22). Compared with placebo, 71% in the rituximab group met the primary endpoint vs 29% in the placebo group. A single dose of 500 mg of rituximab was associated with fewer MG manifestations and showed a reduction in the need for rescue medications compared to placebo. While this study took a novel approach to explore the efficacy of rituximab in patients with MG, a limitation is that the inclusion criteria stipulated a minimum QMG score of 6 (moderate severity), which could have led to some participants displaying an adequate response to limited doses of corticosteroids or immunoglobulins only.

Click to read the study in JAMA Neurology

Click to read an accompanying editorial in JAMA Neurology

Relevant Reading: International Consensus Guidance for Management of Myasthenia Gravis

In-Depth [randomized controlled trial]: This study investigated the efficacy and safety of rituximab compared with placebo for patients with MG. Participants were recruited between October 2016 and March 2020 from regional, community-based catchment areas in Sweden. Among the 87 eligible participants, a total of 25 were randomized to receive rituximab (mean [SD} age, 67.4 [13.4] years; 7 [28%] female) and 22 were randomized to receive placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). The primary endpoint was minimal disease manifestation at 16 weeks as defined by the Quantitative Myasthenia Gravis (QMG) score. A greater proportion of the rituximab group met the primary end point; 71% (17 of 24) vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). The predefined secondary endpoints comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between the arms. In a post-hoc analysis using worst rank imputations for those receiving rescue treatment, change in QMG score between baseline and week 24 favored rituximab over placebo. Fewer patients in the rituximab group required rescue treatment compared with placebo (1 of 25 [4%] in the rituximab group vs 8 of 22 [36%] in the placebo group; PR, 0.11 {95% CI, 0.01-0.81]; P = .008). The rituximab group (n=81) experienced a greater number of adverse events compared with the placebo group (n=44), 6 vs 4 severe adverse events in the rituximab and placebo arms, respectively.

Image: PD

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