Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study

dc.contributor.authorNowak, Richard J.
dc.contributor.authorCoffey, Christopher S.
dc.contributor.authorGoldstein, Jonathan M.
dc.contributor.authorDimachkie, Mazen M.
dc.contributor.authorBenatar, Michael
dc.contributor.authorKissel, John T.
dc.contributor.authorWolfe, Gil I.
dc.contributor.authorBurns, Ted M.
dc.contributor.authorFreimer, Miriam L.
dc.contributor.authorNations, Sharon
dc.contributor.authorGranit, Volkan
dc.contributor.authorSmith, A. Gordon
dc.contributor.authorRichman, David P.
dc.contributor.authorCiafaloni, Emma
dc.contributor.authorAl-Lozi, Muhammad T.
dc.contributor.authorSams, Laura Ann
dc.contributor.authorQuan, Dianna
dc.contributor.authorUbogu, Eroboghene
dc.contributor.authorPearson, Brenda
dc.contributor.authorSharma, Aditi
dc.contributor.authorYankey, Jon W.
dc.contributor.authorUribe, Liz
dc.contributor.authorShy, Michael
dc.contributor.authorAmato, Anthony A.
dc.contributor.authorConwit, Robin
dc.contributor.authorO'Connor, Kevin C.
dc.contributor.authorHafler, David A.
dc.contributor.authorCudkowicz, Merit E.
dc.contributor.authorBarohn, Richard J.
dc.contributor.authorNeuroNEXT NN103 BeatMG Study Team
dc.contributor.departmentNeurology, School of Medicine
dc.date.accessioned2025-03-11T09:31:15Z
dc.date.available2025-03-11T09:31:15Z
dc.date.issued2022-01-25
dc.description.abstractObjective: 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.versionFinal published version
dc.identifier.citationNowak 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.urihttps://hdl.handle.net/1805/46293
dc.language.isoen_US
dc.publisherWolters Kluwer
dc.relation.isversionof10.1212/WNL.0000000000013121
dc.relation.journalNeurology
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectRituximab
dc.subjectAcetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG)
dc.subjectSteroid-sparing effect
dc.titlePhase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
dc.typeArticle
ul.alternative.fulltexthttps://pmc.ncbi.nlm.nih.gov/articles/PMC8793103/
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