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Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus
OBJECTIVE: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. METHODS: Active SLE patients (SLE Disease Activity Ind...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606504/ https://www.ncbi.nlm.nih.gov/pubmed/35798534 http://dx.doi.org/10.1136/ard-2022-222858 |
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author | van Vollenhoven, Ronald F Kalunian, Kenneth C Dörner, Thomas Hahn, Bevra H Tanaka, Yoshiya Gordon, Robert M Shu, Cathye Fei, Kaiyin Gao, Sheng Seridi, Loqmane Gallagher, Patrick Lo, Kim Hung Berry, Pamela Zuraw, Qing C |
author_facet | van Vollenhoven, Ronald F Kalunian, Kenneth C Dörner, Thomas Hahn, Bevra H Tanaka, Yoshiya Gordon, Robert M Shu, Cathye Fei, Kaiyin Gao, Sheng Seridi, Loqmane Gallagher, Patrick Lo, Kim Hung Berry, Pamela Zuraw, Qing C |
author_sort | van Vollenhoven, Ronald F |
collection | PubMed |
description | OBJECTIVE: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. METHODS: Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24. RESULTS: At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event. CONCLUSIONS: Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab. TRIAL REGISTRATION NUMBER: NCT03517722. |
format | Online Article Text |
id | pubmed-9606504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-96065042022-10-28 Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus van Vollenhoven, Ronald F Kalunian, Kenneth C Dörner, Thomas Hahn, Bevra H Tanaka, Yoshiya Gordon, Robert M Shu, Cathye Fei, Kaiyin Gao, Sheng Seridi, Loqmane Gallagher, Patrick Lo, Kim Hung Berry, Pamela Zuraw, Qing C Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVE: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. METHODS: Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24. RESULTS: At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event. CONCLUSIONS: Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab. TRIAL REGISTRATION NUMBER: NCT03517722. BMJ Publishing Group 2022-11 2022-07-07 /pmc/articles/PMC9606504/ /pubmed/35798534 http://dx.doi.org/10.1136/ard-2022-222858 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Systemic Lupus Erythematosus van Vollenhoven, Ronald F Kalunian, Kenneth C Dörner, Thomas Hahn, Bevra H Tanaka, Yoshiya Gordon, Robert M Shu, Cathye Fei, Kaiyin Gao, Sheng Seridi, Loqmane Gallagher, Patrick Lo, Kim Hung Berry, Pamela Zuraw, Qing C Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title | Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title_full | Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title_fullStr | Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title_full_unstemmed | Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title_short | Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
title_sort | phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus |
topic | Systemic Lupus Erythematosus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606504/ https://www.ncbi.nlm.nih.gov/pubmed/35798534 http://dx.doi.org/10.1136/ard-2022-222858 |
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