Rituximab may not significantly reduce steroid use in form of myasthenia gravis

Although rituximab was safe and well tolerated in acetylcholine receptor antibody-positive generalized myasthenia gravis, researchers noted low probability of it significantly reducing steroid use at 1 year.

“The aim of our study was to assess the safety, tolerability and potential benefit of rituximab in acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG) and to identify putative biomarkers predictive of treatment response,” Richard J. Nowak, MD, of the department of neurology at Yale University School of Medicine, and colleagues wrote.

“Our primary goal was to determine whether rituximab warranted a further efficacy trial in the same patient population,” they added. “We limited our study to AChRAb+ patients as they represent the majority of gMG and due to drug availability sample-size constraints and initial feasibility concerns of enrolling only treatment-refractory or muscle-specific kinase antibody-positive (MuSK-Ab+) patients.”

Researchers conducted the randomized, double-blind, placebo-controlled, multicenter, phase 2 trial, called the B-Cell Targeted Treatment in MG, which used a futility design. They included patients aged 21 to 90 years who had AChR-Ab+ gMG and who received prednisone of at least 15 mg per day. A measure of steroid-sparing effect, which the researchers defined as the proportion of patients who achieved 75% or higher reduction in mean daily prednisone dose in the 4 weeks before week 52 and with clinical improvement or no significant worsening compared with the 4-week period before random assignment, served as the primary outcome. Safety served as the co-primary outcome. MG-specific clinical assessment represented secondary outcomes.

Researchers randomly assigned in 52 patients (mean age at enrollment, 55.1 years; 44.2% were women; 59.6% Myasthenia Gravis Foundation of America class II) in a 1:1 ratio to a two-cycle rituximab or placebo regimen, with follow-up through 52 weeks and a mean baseline prednisone dose of 22.1 mg per day.

Results showed 60% of patients on rituximab achieved the primary steroid-sparing outcome compared with 56% of patients on placebo. Nowak and colleagues noted the unlikelihood of achieving the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo in a subsequent, larger trial because the study reached its futility endpoint (P = .03). They reported no safety issues.

“Additional analyses are planned to delve deeper into these results, and to further explore the role of B-cell depletion in this population, including the full impact of disease

severity, B-cell counts and use of concomitant [immunosuppressive therapies] ISTs at time of enrollment,” the researchers wrote. “Further insights are anticipated from the observational, post-intervention study, which include follow-up through 96 weeks.”