Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
dc.contributor.author | Nowak, Richard J. | |
dc.contributor.author | Coffey, Christopher S. | |
dc.contributor.author | Goldstein, Jonathan M. | |
dc.contributor.author | Dimachkie, Mazen M. | |
dc.contributor.author | Benatar, Michael | |
dc.contributor.author | Kissel, John T. | |
dc.contributor.author | Wolfe, Gil I. | |
dc.contributor.author | Burns, Ted M. | |
dc.contributor.author | Freimer, Miriam L. | |
dc.contributor.author | Nations, Sharon | |
dc.contributor.author | Granit, Volkan | |
dc.contributor.author | Smith, A. Gordon | |
dc.contributor.author | Richman, David P. | |
dc.contributor.author | Ciafaloni, Emma | |
dc.contributor.author | Al-Lozi, Muhammad T. | |
dc.contributor.author | Sams, Laura Ann | |
dc.contributor.author | Quan, Dianna | |
dc.contributor.author | Ubogu, Eroboghene | |
dc.contributor.author | Pearson, Brenda | |
dc.contributor.author | Sharma, Aditi | |
dc.contributor.author | Yankey, Jon W. | |
dc.contributor.author | Uribe, Liz | |
dc.contributor.author | Shy, Michael | |
dc.contributor.author | Amato, Anthony A. | |
dc.contributor.author | Conwit, Robin | |
dc.contributor.author | O'Connor, Kevin C. | |
dc.contributor.author | Hafler, David A. | |
dc.contributor.author | Cudkowicz, Merit E. | |
dc.contributor.author | Barohn, Richard J. | |
dc.contributor.author | NeuroNEXT NN103 BeatMG Study Team | |
dc.contributor.department | Neurology, School of Medicine | |
dc.date.accessioned | 2025-03-11T09:31:15Z | |
dc.date.available | 2025-03-11T09:31:15Z | |
dc.date.issued | 2022-01-25 | |
dc.description.abstract | Objective: To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). Methods: The 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/day 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 co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks. Results: Of the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. 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 pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified. Conclusions: While 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-moderately symptomatic AChR-Ab+ gMG. Classification of evidence: This 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. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Nowak RJ, Coffey CS, Goldstein JM, et al. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology. 2022;98(4):e376-e389. Published 2022 Jan 25. doi:10.1212/WNL.0000000000013121 | |
dc.identifier.uri | https://hdl.handle.net/1805/46293 | |
dc.language.iso | en_US | |
dc.publisher | Wolters Kluwer | |
dc.relation.isversionof | 10.1212/WNL.0000000000013121 | |
dc.relation.journal | Neurology | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Rituximab | |
dc.subject | Acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG) | |
dc.subject | Steroid-sparing effect | |
dc.title | Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study | |
dc.type | Article | |
ul.alternative.fulltext | https://pmc.ncbi.nlm.nih.gov/articles/PMC8793103/ |