Safety and efficacy of abatacept in patients with treatment-resistant SARCoidosis (ABASARC) – protocol for a multi-center, single-arm phase IIa trial
| Autor: | Annette Uhlmann, Gernot Zissel, BC Frye, Fabian Schubach, Joachim Müller Quernheim, Bodo Grimbacher, Ina Caroline Rump, Gabriele Ihorst |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Systemic disease Regulatory T-cells GHS general health score Phases of clinical research King's sarcoidosis questionnaire Article Abatacept 18FDG-PET-CT 18Fluor-Desoxy-Glucose positron-emission tomography combined with computer tomography 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical endpoint EBV Epstein-Barr-Virus 030212 general & internal medicine Patient-reported outcome KSQ King's sarcoidosis questionnaire Pharmacology lcsh:R5-920 business.industry Chronic sarcoidosis TLC total lung capacity General Medicine medicine.disease IFN-γ Interferon-γ CMV cytomegaly-virus IL interleukin Clinical trial Rheumatoid arthritis FVC forced vital capacity Prednisolone Sarcoidosis Therapy BAL bronchoalveolar lavage business lcsh:Medicine (General) TReg regulatory T-cells TNF tumor-necrosis factor 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Contemporary Clinical Trials Communications Contemporary Clinical Trials Communications, Vol 19, Iss, Pp 100575-(2020) |
| ISSN: | 2451-8654 |
| Popis: | Introduction Sarcoidosis is a granulomatous systemic disease that becomes chronic in approximately one third of affected patients resulting in quality of life and functional impairment. Immunosuppressive drugs other than steroids represent alternative therapeutic options, but side effects like liver and bone marrow toxicity or increased susceptibility to infections limit their use. Pathophysiological studies in sarcoidosis patients demonstrate altered regulatory T-cell functions with a reduced expression of CTLA-4 (CD152) and prolonged inflammation. Therefore, interfering with CTLA-4 using abatacept might be a therapeutic option in sarcoidosis similar to rheumatoid arthritis therapy. Methods/design This is a multicenter prospective open-labeled single arm phase II study addressing the safety of abatacept in sarcoidosis patients. 30 patients with chronic sarcoidosis requiring immunosuppressive therapy beyond 5 mg prednisolone equivalent will be treated with abatacept in combination with corticosteroids for one year in two centers. The primary endpoint is the number and characterization of severe infectious complications under treatment with abatacept. Secondary endpoints are the rate of all infections, patient-related outcomes (assessed by questionnaires), lung function and immunological parameters including alveolar inflammation assessed by bronchoaveolar lavage. Discussion This is the first trial of abatacept in patients with sarcoidosis. It is hypothesized that administration of abatacept is safe in patients with chronic sarcoidosis and can limit ongoing inflammation. Patients’ wellbeing is assessed by established questionnaires. Immunological work-up will highlight the effect of abatacept on inflammatory pathways in sarcoidosis. Trial registration The trial has been registered at the German Clinical Trial Registry (Deutsches Register Klinischer Studien, DRKS) with the identity number DRKS00011660. |
| Databáze: | OpenAIRE |
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