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

Autor: Schmidt WA; Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Lindenberger Weg 19, Berlin, 13125, Germany. wolfgang.schmidt@immanuelalbertinen.de., Dasgupta B; Southend University Hospital, Mid and South Essex NHS Foundation Trust, Essex, UK., Sloane J; Sanofi, Cambridge, MA, USA., Giannelou A; Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA., Xu Y; Sanofi, Bridgewater, NJ, USA., Unizony SH; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Mackie SL; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Gonzalez-Gay MA; Rheumatology Division, IIS-Fundación Jiménez Díaz, Madrid, Spain.; University of Cantabria, IDIVAL, Santander, Spain., Spiera R; Department of Medicine, Hospital for Special Surgery, New York, NY, USA., Warrington KJ; Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA., Villiger PM; Rheumatology and Clinical Immunology, Medical Center Monbijou, Bern, Switzerland., Nivens MC; Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA., Akinlade B; Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA., Lin Y; Sanofi, Bridgewater, NJ, USA., Buttgereit F; Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany., Stone JH; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2023 Oct 16; Vol. 25 (1), pp. 199. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1186/s13075-023-03177-6
Abstrakt: Background: Giant 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.
Methods: This 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.
Results: Of 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.
Conclusions: Owing 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 Registration: ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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