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Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis
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 participant...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902787/ https://www.ncbi.nlm.nih.gov/pubmed/29661905 http://dx.doi.org/10.1212/WNL.0000000000005323 |
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author | Hewett, Karen Sanders, Donald B. Grove, Richard A. Broderick, Christine L. Rudo, Todd J. Bassiri, Ashlyn Zvartau-Hind, Marina Bril, Vera |
author_facet | Hewett, Karen Sanders, Donald B. Grove, Richard A. Broderick, Christine L. Rudo, Todd J. Bassiri, Ashlyn Zvartau-Hind, Marina Bril, Vera |
author_sort | Hewett, Karen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5902787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-59027872018-04-17 Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis Hewett, Karen Sanders, Donald B. Grove, Richard A. Broderick, Christine L. Rudo, Todd J. Bassiri, Ashlyn Zvartau-Hind, Marina Bril, Vera Neurology Article 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. Lippincott Williams & Wilkins 2018-04-17 /pmc/articles/PMC5902787/ /pubmed/29661905 http://dx.doi.org/10.1212/WNL.0000000000005323 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Hewett, Karen Sanders, Donald B. Grove, Richard A. Broderick, Christine L. Rudo, Todd J. Bassiri, Ashlyn Zvartau-Hind, Marina Bril, Vera Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title | Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title_full | Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title_fullStr | Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title_full_unstemmed | Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title_short | Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
title_sort | randomized study of adjunctive belimumab in participants with generalized myasthenia gravis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902787/ https://www.ncbi.nlm.nih.gov/pubmed/29661905 http://dx.doi.org/10.1212/WNL.0000000000005323 |
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