Nowak, Richard J.Coffey, Christopher S.Goldstein, Jonathan M.Dimachkie, Mazen M.Benatar, MichaelKissel, John T.Wolfe, Gil I.Burns, Ted M.Freimer, Miriam L.Nations, SharonGranit, VolkanSmith, A. GordonRichman, David P.Ciafaloni, EmmaAl-Lozi, Muhammad T.Sams, Laura AnnQuan, DiannaUbogu, EroboghenePearson, BrendaSharma, AditiYankey, Jon W.Uribe, LizShy, MichaelAmato, Anthony A.Conwit, RobinO'Connor, Kevin C.Hafler, David A.Cudkowicz, Merit E.Barohn, Richard J.NeuroNEXT NN103 BeatMG Study Team2025-03-112025-03-112022-01-25Nowak 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.0000000000013121https://hdl.handle.net/1805/46293Objective: 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.en-USPublisher PolicyRituximabAcetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG)Steroid-sparing effectArticle