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

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013121
Author(s):  
Richard J Nowak ◽  
Christopher S. Coffey ◽  
Jonathan M. Goldstein ◽  
Mazen M. Dimachkie ◽  
Michael Benatar ◽  
...  

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

2010 ◽  
Vol 81 (5) ◽  
pp. 586-587 ◽  
Author(s):  
H. Koike ◽  
S. Koyano ◽  
S. Morozumi ◽  
Y. Kawagashira ◽  
M. Iijima ◽  
...  

BMJ ◽  
1977 ◽  
Vol 1 (6075) ◽  
pp. 1512-1512 ◽  
Author(s):  
G K Scadding ◽  
H C Thomas ◽  
C W Havard

2014 ◽  
Vol 49 (4) ◽  
pp. 483-486 ◽  
Author(s):  
Donald B. Sanders ◽  
Ted M. Burns ◽  
Gary R. Cutter ◽  
Janice M. Massey ◽  
Vern C. Juel ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document