1. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis.
- Author
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Hewett K, Sanders DB, Grove RA, Broderick CL, Rudo TJ, Bassiri A, Zvartau-Hind M, and Bril V
- Subjects
- Activities of Daily Living psychology, Aged, Antibodies blood, Antibodies, Monoclonal, Humanized pharmacokinetics, Double-Blind Method, Female, Follow-Up Studies, Humans, Immunosuppressive Agents pharmacokinetics, International Cooperation, Male, Middle Aged, Myasthenia Gravis blood, Myasthenia Gravis psychology, Receptor Protein-Tyrosine Kinases immunology, Receptors, Cholinergic immunology, Time Factors, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Immunosuppressive Agents therapeutic use, Myasthenia Gravis drug therapy
- Abstract
Objective: To investigate the efficacy and safety of belimumab, a fully human immunoglobulin G1λ monoclonal antibody against B-lymphocyte stimulator, in participants with generalized myasthenia gravis (MG) who remained symptomatic despite standard of care (SoC) therapy., Methods: Eligible participants with MG were randomized 1:1 to receive IV belimumab 10 mg/kg or placebo in this phase II, placebo-controlled, multicenter, double-blind study (NCT01480596; BEL115123). Participants received SoC therapies throughout the 24-week treatment phase and 12-week follow-up period. The primary efficacy endpoint was mean change from baseline in the Quantitative Myasthenia Gravis (QMG) scale at week 24; safety assessments included the frequency and severity of adverse events (AEs) and serious AEs., Results: Forty participants were randomized (placebo n = 22; belimumab n = 18). The mean change in QMG score from baseline at week 24 was not significantly different for belimumab vs placebo ( p = 0.256). There were no statistically significant differences between treatment groups for secondary endpoints, including the MG Composite and MG-Activity of Daily Living scores. Acetylcholine receptor antibody levels decreased over time in both treatment groups. No unexpected AEs were identified and occurrence was similar in the belimumab (78%) and placebo (91%) groups. One participant receiving placebo died (severe sepsis) during the treatment phase., Conclusions: The primary endpoint was not met for belimumab in participants with generalized MG receiving SoC. There was no significant difference in mean change in the QMG score at week 24 for belimumab vs placebo. The safety profile of belimumab was consistent with previous systemic lupus erythematosus studies., Classification of Evidence: This study provides Class I evidence that for participants with generalized MG, belimumab did not significantly improve QMG score compared with placebo., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2018
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