Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis
Year: 2021
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Background and ObjectiveTo determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG). MethodsThe B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase 2 trial that utilized a futility design. Individuals 21–90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II–IV) and receiving prednisone ≥15 mg/d were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The coprimary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to a 2-cycle rituximab/placebo regimen, with follow-up through 52 weeks. ResultsOf the 52 participants included, mean ± SD age at enrollment was 55.1 ± 17.1 years; 23 (44.2%) were women and 31 (59.6%) were Myasthenia Gravis Foundation of America Class II. The mean ± SD baseline prednisone dose was 22.1 ± 9.7 mg/d. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs 56% on placebo. The study reached its futility endpoint (p = 0.03), suggesting that the predefined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues were identified. DiscussionAlthough rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase 3 trial of mild to moderately symptomatic AChR-Ab+ gMG. Classification of EvidenceThis study provides Class I evidence that for mild to moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.
Source: Neurology
Authors: Richard J. Nowak, Christopher S. Coffey, Jonathan M. Goldstein, Mazen M. Dimachkie, Michael Benatar, John T. Kissel, Gil I. Wolfe, Ted M. Burns, Miriam L. Freimer, Sharon Nations, Volkan Granit, A. Gordon Smith, David P. Richman, Emma Ciafaloni, Muhammad T. Al-Lozi, Laura Ann Sams, Dianna Quan, Eroboghene Ubogu, Brenda Pearson, Aditi Sharma, Jon W. Yankey, Liz Uribe, Michael Shy, Anthony A. Amato, Robin Conwit, Kevin C. O'Connor, David A. Hafler, Merit E. Cudkowicz, Richard J. Barohn, on behalf of the NeuroNEXT NN103 BeatMG Study Team
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Bristol-Myers Squibb, Charcot-Marie-Tooth Association, Myasthenia Gravis Foundation of America, Sanofi, Muscular Dystrophy Association, Yale University, Biogen, Parent Project Muscular Dystrophy, Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Ohio State University, State University of New York, University of Rochester, University of Cincinnati, CSL Behring, PTC Therapeutics, aTyr, Cytokinetics, Sarepta Therapeutics, Amicus Therapeutics, University of Oxford, Grifols, National Institutes of Health, Centers for Disease Control and Prevention, Genentech, Weill Cornell Medical College, University at Buffalo, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G161547206, A Phase II Trial of Rituximab In Myasthenia Gravis, Clinical Centers for the NINDS NeuroNEXT(Network of Excellence in Neuroscience Clinical Trials) Consortium, Clinical Coordinating Center for the Network of Excellence in Neuroscience Clinical Trials (NEXT - CCC), Washington University Institute of Clinical and Translational Sciences, Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT) DCC, Yale Clinical and Translational Science Award, Mechanisms of autoimmunity in myasthenia gravis
OpenAlex ID: W3217619127