A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis

Arthritis Research & Therapy

Research

Robert Spiera¹  Frank Buttgereit²  Kenneth J. Warrington³  Sarah L. Mackie⁴  John H. Stone⁵  Sebastian H. Unizony⁵  Wolfgang A. Schmidt⁶  Michael C. Nivens⁷  Angeliki Giannelou⁷  Bolanle Akinlade⁷  Miguel A. Gonzalez-Gay⁸  Peter M. Villiger⁹  Yong Lin^1,10  Yuqing Xu^1,10  Jennifer Sloane^1,11  Bhaskar Dasgupta^1,12 

[1] Department of Medicine, Hospital for Special Surgery, New York, NY, USA;Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany;Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA;Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK;Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK;Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Lindenberger Weg 19, 13125, Berlin, Germany;Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA;Rheumatology Division, IIS-Fundación Jiménez Díaz, Madrid, Spain;University of Cantabria, IDIVAL, Santander, Spain;Rheumatology and Clinical Immunology, Medical Center Monbijou, Bern, Switzerland;Sanofi, Bridgewater, NJ, USA;Sanofi, Cambridge, MA, USA;Southend University Hospital, Mid and South Essex NHS Foundation Trust, Essex, UK;

关键词: Sarilumab;    Giant cell arteritis;    Glucocorticoids;    Interleukin-6;    Sustained remission;   

DOI  :  10.1186/s13075-023-03177-6

 received in 2023-07-03, accepted in 2023-09-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGiant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA.MethodsThis Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized.ResultsOf the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n = 6/13) of patients in SAR200 + 26W, 43% (n = 3/7) in SAR150 + 26W, 30% (n = 3/10) in PBO + 52W, and 0 (n = 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (n = 6/10) in PBO + 52W and 17% (n = 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n = 6/13, SAR200 + 26W), 43% (n = 3/7, SAR150 + 26W), 60% (n = 6/10, PBO + 52W), and 33% (n = 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80–100%) experienced treatment-emergent adverse events, with similar incidences reported across groups.ConclusionsOwing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings.Trial registrationClinicalTrials.gov NCT03600805. Registered on July 26, 2018.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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