Journal article
Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
Neurology, Vol.98(4), pp.E376-E389
12/02/2021
DOI: 10.1212/WNL.0000000000013121
PMCID: PMC8793103
PMID: 34857535
Abstract
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).
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
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT02110706.
Details
- Title: Subtitle
- Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
- Creators
- Richard J Nowak - Department of Neurology, Yale University School of Medicine, New Haven, CT richard.nowak@yale.eduChristopher S Coffey - Clinical Trials Statistical & Data Management Center, University of Iowa, Iowa City, IAJonathan M Goldstein - Department of Neurology, Hospital for Special Surgery, New York, NYMazen M Dimachkie - Department of Neurology, Kansas University School of Medicine, Kansas City, KSMichael Benatar - Department of Neurology, University of Miami Miller School of Medicine, Miami, FLJohn T Kissel - Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OHGil I Wolfe - Department of Neurology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NYTed M Burns - Department of Neurology, University of Virginia School of Medicine, Charlottesville, VAMiriam L Freimer - Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OHSharon Nations - Department of Neurology, University of Texas Southwestern Medical School, Dallas, TXVolkan Granit - Department of Neurology, University of Miami Miller School of Medicine, Miami, FLA Gordon Smith - Department of Neurology, University of Utah School of Medicine, Salt Lake City, UTDavid P Richman - Department of Neurology, University of California Davis School of Medicine, Sacramento, CAEmma Ciafaloni - Department of Neurology, University of Rochester School of Medicine & Dentistry, Rochester, NYMuhammad T Al-Lozi - Department of Neurology, Washington University School of Medicine, St. Louis, MOLaura Ann Sams - Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OHDianna Quan - Department of Neurology, University of Colorado School of Medicine, Aurora, COEroboghene Ubogu - Department of Neurology, The University of Alabama at Birmingham School of Medicine, Birmingham, ALBrenda Pearson - Clinical Trials Statistical & Data Management Center, University of Iowa, Iowa City, IAAditi Sharma - Department of Neurology, University of Iowa, Iowa City, IAJon W Yankey - Clinical Trials Statistical & Data Management Center, University of Iowa, Iowa City, IALiz Uribe - Clinical Trials Statistical & Data Management Center, University of Iowa, Iowa City, IAMichael Shy - Department of Neurology, University of Iowa, Carver College of Medicine, Iowa City, IAAnthony A Amato - Department of Neurology, Brigham and Women's Hospital, Boston, MARobin Conwit - Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Rockville, MDKevin C O'Connor - Department of Neurology, Yale University School of Medicine, New Haven, CTDavid A Hafler - Department of Neurology, Yale University School of Medicine, New Haven, CTMerit E Cudkowicz - Department of Neurology, Massachusetts General Hospital, Boston, MARichard J Barohn - Department of Neurology, University of Missouri, Columbia, MONeuroNEXT NN103 BeatMG Study Team
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.98(4), pp.E376-E389
- DOI
- 10.1212/WNL.0000000000013121
- PMID
- 34857535
- PMCID
- PMC8793103
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Language
- English
- Date published
- 12/02/2021
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984214852302771
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