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Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial
OBJECTIVE: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes. METHODS: Patients were enrolled if they were refr...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634756/ https://www.ncbi.nlm.nih.gov/pubmed/26539981 http://dx.doi.org/10.1371/journal.pone.0133702 |
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author | Allenbach, Yves Guiguet, Marguerite Rigolet, Aude Marie, Isabelle Hachulla, Eric Drouot, Laurent Jouen, Fabienne Jacquot, Serge Mariampillai, Kuberaka Musset, Lucile Grenier, Philippe Devilliers, Herve Hij, Adrian Boyer, Olivier Herson, Serge Benveniste, Olivier |
author_facet | Allenbach, Yves Guiguet, Marguerite Rigolet, Aude Marie, Isabelle Hachulla, Eric Drouot, Laurent Jouen, Fabienne Jacquot, Serge Mariampillai, Kuberaka Musset, Lucile Grenier, Philippe Devilliers, Herve Hij, Adrian Boyer, Olivier Herson, Serge Benveniste, Olivier |
author_sort | Allenbach, Yves |
collection | PubMed |
description | OBJECTIVE: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes. METHODS: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants. RESULTS: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48–11,718) to 74.5 IU/L (range, 40–47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10–70) to 9 mg/d (range, 7–65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1. CONCLUSIONS: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT00774462. |
format | Online Article Text |
id | pubmed-4634756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46347562015-11-13 Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial Allenbach, Yves Guiguet, Marguerite Rigolet, Aude Marie, Isabelle Hachulla, Eric Drouot, Laurent Jouen, Fabienne Jacquot, Serge Mariampillai, Kuberaka Musset, Lucile Grenier, Philippe Devilliers, Herve Hij, Adrian Boyer, Olivier Herson, Serge Benveniste, Olivier PLoS One Research Article OBJECTIVE: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes. METHODS: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants. RESULTS: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48–11,718) to 74.5 IU/L (range, 40–47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10–70) to 9 mg/d (range, 7–65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1. CONCLUSIONS: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT00774462. Public Library of Science 2015-11-05 /pmc/articles/PMC4634756/ /pubmed/26539981 http://dx.doi.org/10.1371/journal.pone.0133702 Text en © 2015 Allenbach et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Allenbach, Yves Guiguet, Marguerite Rigolet, Aude Marie, Isabelle Hachulla, Eric Drouot, Laurent Jouen, Fabienne Jacquot, Serge Mariampillai, Kuberaka Musset, Lucile Grenier, Philippe Devilliers, Herve Hij, Adrian Boyer, Olivier Herson, Serge Benveniste, Olivier Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title | Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title_full | Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title_fullStr | Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title_full_unstemmed | Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title_short | Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial |
title_sort | efficacy of rituximab in refractory inflammatory myopathies associated with anti- synthetase auto-antibodies: an open-label, phase ii trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634756/ https://www.ncbi.nlm.nih.gov/pubmed/26539981 http://dx.doi.org/10.1371/journal.pone.0133702 |
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