| Title: |
Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis |
| Authors: |
Nowak, Richard J; Coffey, Christopher S; Goldstein, Jonathan M; Dimachkie, Mazen M; Benatar, Michael; Kissel, John T; Wolfe, Gil I; Burns, Ted M; Freimer, Miriam L; Nations, Sharon; Granit, Volkan; Smith, A Gordon; Richman, David P; Ciafaloni, Emma; Al-Lozi, Muhammad T; Sams, Laura Ann; Quan, Dianna; Ubogu, Eroboghene; Pearson, Brenda; Sharma, Aditi; Yankey, Jon W; Uribe, Liz; Shy, Michael; Amato, Anthony A; Conwit, Robin; O'Connor, Kevin C; Hafler, David A; Cudkowicz, Merit E; Barohn, Richard J |
| Source: |
Neurology, vol 98, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2022 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Clinical Trials and Supportive Activities (rcdc); Rare Diseases (rcdc); Myasthenia Gravis (rcdc); Clinical Research (rcdc); Neurosciences (rcdc); Autoimmune Disease (rcdc); 6.1 Pharmaceuticals (hrcs-rac); NeuroNEXT NN103 BeatMG Study Team; 1103 Clinical Sciences (for); 1109 Neurosciences (for); 1702 Cognitive Sciences (for); Neurology & Neurosurgery (science-metrix); 3209 Neurosciences (for-2020) |
| Subject Geographic: |
e376 - e389 |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt3kc6g1jn; https://escholarship.org/uc/item/3kc6g1jn; https://escholarship.org/content/qt3kc6g1jn/qt3kc6g1jn.pdf |
| DOI: |
10.1212/wnl.0000000000013121 |
| Availability: |
https://escholarship.org/uc/item/3kc6g1jn; https://escholarship.org/content/qt3kc6g1jn/qt3kc6g1jn.pdf; https://doi.org/10.1212/wnl.0000000000013121 |
| Rights: |
public |
| Accession Number: |
edsbas.B64495DF |
| Database: |
BASE |