Rituximab effectively and safely allows patients with new-onset generalized myasthenia gravis (MG) to achieve minimal disease manifestations without rescue treatments and using low doses of corticosteroids, according to study findings published in JAMA Neurology.
Among patients with MG, most carry serum acetylcholine receptor antibodies, but, a portion of patients lack antibodies to known antigenic targets. Current guidelines suggest oral corticosteroids as the first-line therapy for MG and biological treatments as third-line options. For the JAMA Neurology study, researchers sought to explore the efficacy and safety of rituximab compared with placebo as an add-on to the standard of care for patients with new-onset MG.
Researchers in Sweden conducted a 48-week, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT02950155), identifying 87 potentially eligible patients screened for new-onset generalized MG at 7 regional clinics between October 20, 2016 and March 2, 2020. They randomly assigned 25 patients to the intervention group (Mean [SD], age, 67.4 [13.4] years; 7 [28%] women) and 22 patients to the placebo group (mean [SD] age, 58 [18.6] years; 7 [32%] women) with 1 patient in each group unable to complete the study.
Patients in the intervention group received intravenous infusions of 500 mg of rituximab along with 1000 mg of paracetamol, 10 mg of cetirizine, and 50 mg of prednisone prior to infusion.
Patients received additional treatments of plasma exchange or intravenous immunoglobulins as needed during the first 8 weeks of treatment. Prednisolone dose was limited to 10 mg/day after the 8 initial weeks.
The primary outcome was the amount of patients with minimal disease manifestation, defined by the Quantitative Myasthenia Gravis (QMG) score, at 16 weeks.
The researchers assessed the efficacy of rituximab compared with baseline measures at weeks 16, 24, 36, and 48, using the QMG, the Myasthenia Gravis Activity of Daily Life (MG-ADL), and the Myasthenia Gravis Quality of Life (MG-QoL) functional outcome measures.
After 16 weeks, 17 (71%) of 24 patients in the rituximab group achieved minimal disease manifestations as evidenced by scoring 4 or less on the QMG score plus taking 10 mg/day or less of prednisolone daily compared with 6 (29%) of 21 patients in the placebo group (probability ratio [PR]: 2.48; 95% CI, 1.20-5.11; P =.007). The researchers observed similar trends in support of the treatment arm compared with placebo at weeks 24, 36, and 48.
MG-ADL and MG-QoL scores did not differ significantly between groups at week 16, nor did QMG at week 24, when censoring for rescue treatments. However, these scores changed more favorably in the rituximab group after accounting for rescue treatments.
Rescue treatments occurred more frequently in the placebo group compared with the treatment group (rituximab: 1 [4%] vs. placebo: 8 [36%]; PR: 0.11; 95% CI, 0.01-0.81; P =.008).
One patient with pre-existing ischemic heart disease in the rituximab group experienced a fatal cardiac event, while 2 patients in the placebo group experienced life-threatening events including cardiac arrest during a MG exacerbation and bacterial septicemia during a MG crisis. The remaining adverse reactions were mild in nature, including infusion reactions in 3 patients in the treatment group and 1 in the placebo group.
“Allocation to a low-dose rituximab protocol resulted in a higher proportion of patients with minimal disease manifestations, despite low corticosteroid doses and no use of rescue therapies, at 16 weeks compared with placebo,” the researchers stated.
They concluded, “Treatment with rituximab can be considered early after onset of generalized myasthenia gravis to reduce the risk of disease worsening and/or need of additional therapies.”
Study limitations included imbalanced baseline patient characteristics, censoring rescue treatments which impacted assessment of secondary outcome measures, and inclusion criteria restricting included patients to a QMG score of 6 or higher which excluded patients with milder MG presentations.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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. Published online September 19, 2022. doi:10.1001/jamaneurol.2022.2887