A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis
Abstract 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 sa...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-023-03177-6 |
| _version_ | 1827709163928551424 |
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| author | Wolfgang A. Schmidt Bhaskar Dasgupta Jennifer Sloane Angeliki Giannelou Yuqing Xu Sebastian H. Unizony Sarah L. Mackie Miguel A. Gonzalez-Gay Robert Spiera Kenneth J. Warrington Peter M. Villiger Michael C. Nivens Bolanle Akinlade Yong Lin Frank Buttgereit John H. Stone |
| author_facet | Wolfgang A. Schmidt Bhaskar Dasgupta Jennifer Sloane Angeliki Giannelou Yuqing Xu Sebastian H. Unizony Sarah L. Mackie Miguel A. Gonzalez-Gay Robert Spiera Kenneth J. Warrington Peter M. Villiger Michael C. Nivens Bolanle Akinlade Yong Lin Frank Buttgereit John H. Stone |
| author_sort | Wolfgang A. Schmidt |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:17:06Z |
| format | Article |
| id | doaj.art-4519641ec60d4627b6d5c6d36c1bb6ac |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-10T17:17:06Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
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| series | Arthritis Research & Therapy |
| spelling | doaj.art-4519641ec60d4627b6d5c6d36c1bb6ac2023-11-20T10:27:13ZengBMCArthritis Research & Therapy1478-63622023-10-0125111610.1186/s13075-023-03177-6A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritisWolfgang A. Schmidt0Bhaskar Dasgupta1Jennifer Sloane2Angeliki Giannelou3Yuqing Xu4Sebastian H. Unizony5Sarah L. Mackie6Miguel A. Gonzalez-Gay7Robert Spiera8Kenneth J. Warrington9Peter M. Villiger10Michael C. Nivens11Bolanle Akinlade12Yong Lin13Frank Buttgereit14John H. Stone15Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus BerlinSouthend University Hospital, Mid and South Essex NHS Foundation TrustSanofiRegeneron Pharmaceuticals, IncSanofiMassachusetts General Hospital, Harvard Medical SchoolLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of LeedsRheumatology Division, IIS-Fundación Jiménez DíazDepartment of Medicine, Hospital for Special SurgeryDivision of Rheumatology, Department of Medicine, Mayo ClinicRheumatology and Clinical Immunology, Medical Center MonbijouRegeneron Pharmaceuticals, IncRegeneron Pharmaceuticals, IncSanofiDepartment of Rheumatology and Clinical Immunology, Charité Universitätsmedizin BerlinMassachusetts General Hospital, Harvard Medical SchoolAbstract 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.https://doi.org/10.1186/s13075-023-03177-6SarilumabGiant cell arteritisGlucocorticoidsInterleukin-6Sustained remission |
| spellingShingle | Wolfgang A. Schmidt Bhaskar Dasgupta Jennifer Sloane Angeliki Giannelou Yuqing Xu Sebastian H. Unizony Sarah L. Mackie Miguel A. Gonzalez-Gay Robert Spiera Kenneth J. Warrington Peter M. Villiger Michael C. Nivens Bolanle Akinlade Yong Lin Frank Buttgereit John H. Stone 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 Sarilumab Giant cell arteritis Glucocorticoids Interleukin-6 Sustained remission |
| title | A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| title_full | A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| title_fullStr | A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| title_full_unstemmed | A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| title_short | A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| title_sort | phase 3 randomized double blind placebo controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis |
| topic | Sarilumab Giant cell arteritis Glucocorticoids Interleukin-6 Sustained remission |
| url | https://doi.org/10.1186/s13075-023-03177-6 |
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