PT  - JOURNAL ARTICLE
AU  - Nowak, Richard J
AU  - Coffey, Christopher S.
AU  - Goldstein, Jonathan M.
AU  - Dimachkie, Mazen M.
AU  - Benatar, Michael
AU  - Kissel, John T
AU  - Wolfe, Gil I.
AU  - Burns, Ted M.
AU  - Freimer, Miriam L
AU  - Nations, Sharon
AU  - Granit, Volkan
AU  - Smith, A. Gordon
AU  - Richman, David P.
AU  - Ciafaloni, Emma
AU  - Al-Lozi, Muhammad T.
AU  - Sams, Laura Ann
AU  - Quan, Dianna
AU  - Ubogu, Eroboghene
AU  - Pearson, Brenda
AU  - Sharma, Aditi
AU  - Yankey, Jon W.
AU  - Uribe, Liz
AU  - Shy, Michael
AU  - Amato, Anthony A.
AU  - Conwit, Robin
AU  - O'Connor, Kevin C.
AU  - Hafler, David A.
AU  - Cudkowicz, Merit E.
AU  - Barohn, Richard J.
AU  - NeuroNEXT NN103 BeatMG Study Team
TI  - Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
AID  - 10.1212/WNL.0000000000013121
DP  - 2021 Dec 02
TA  - Neurology
PG  - 10.1212/WNL.0000000000013121
4099  - http://n.neurology.org/content/early/2021/12/02/WNL.0000000000013121.short
4100  - http://n.neurology.org/content/early/2021/12/02/WNL.0000000000013121.full
AB  - 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02110706