Academic Journal
Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial
| العنوان: | Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial |
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| المؤلفون: | Benveniste, Olivier, Hogrel, Jean-Yves, Belin, Lisa, Annoussamy, Mélanie, Bachasson, Damien, Rigolet, Aude, Laforêt, Pascal, Dzangue-Tchoupou, Gaelle, Salem, Joe-Elie, Nguyen, Lee, S, Stojkovic, Tanya, Zahr, Noel, Hervier, Baptiste, Landon-Cardinal, Océane, Behin, Anthony, Guilloux, Edith, Reyngoudt, Harmen, Amelin, Damien, Uruha, Akinori, Mariampillai, Kuberaka, Marty, Benjamin, Eymard, Bruno, Hulot, Jean-Sébastien, Greenberg, Steven, A, Carlier, Pierre, G, Allenbach, Yves |
| المساهمون: | Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), CHU Trousseau APHP, Centre d'investigation clinique Paris Est CHU Pitié Salpêtrière (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montréal (UdeM), Harvard Medical School Boston (HMS), Institut national de la santé et de la recherche médicale, Direction générale de l'offre de soins, and Association Française contre les Myopathies., ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011) |
| المصدر: | ISSN: 2665-9913 ; The Lancet Rheumatology ; https://hal.sorbonne-universite.fr/hal-03180889 ; The Lancet Rheumatology, 2021, 3 (1), pp.e40-e48. ⟨10.1016/S2665-9913(20)30280-0⟩. |
| بيانات النشر: | CCSD Elsevier |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy |
| الوصف: | International audience ; Background: Inclusion body myositis is the most frequent myositis in patients older than 50 years. Classical immunosuppressants are ineffective in treating inclusion body myositis, and to date there are no recommendations for pharmacological approaches to treatment. When used after organ transplantation, sirolimus can block the proliferation of effector T cells, while preserving T regulatory cells, and induce autophagy, all of which are processes that are impaired in inclusion body myositis. In this pilot study, we aimed to test the efficacy of sirolimus in patients with inclusion body myositis.Methods: This randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial was done at a single hospital in Paris, France. The study included men and women (aged 45–80 years) who had a defined diagnosis of inclusion body myositis according to established criteria. Eligible participants were randomly assigned (1:1) to receive once-daily oral sirolimus 2 mg or placebo. Centralised balanced block randomisation (blocks of four) was computer generated without stratification. The study comprised a 15-day screening period (days −15 to 0) and a 52-week treatment period (day 0 to month 12). The primary endpoint was the relative percentage change from baseline to month 12 in maximal voluntary isometric knee extension strength. Secondary endpoints included the following assessments at months 6 and 12: 6-min walking distance, isometric muscle strength for hand grip (finger flexors), knee flexion and elbow flexion and extension, forced vital capacity, muscle replacement with fat measured by quantitative nuclear MRI, Inclusion Body Myositis Weakness Composite Index (IBMWCI), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Health Assessment Questionnaire without Disability Index (HAQ-DI), and analyses of T-cell subpopulations by mass cytometry. The primary analysis was done on the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02481453.Findings: ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1016/S2665-9913(20)30280-0 |
| الاتاحة: | https://hal.sorbonne-universite.fr/hal-03180889 https://hal.sorbonne-universite.fr/hal-03180889v1/document https://hal.sorbonne-universite.fr/hal-03180889v1/file/Benveniste%20et%20al.%20-%202021%20-%20Sirolimus%20for%20treatment%20of%20patients%20with%20inclusion%20%281%29.pdf https://doi.org/10.1016/S2665-9913(20)30280-0 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.5075B7F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/S2665-9913(20)30280-0 |
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