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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
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.
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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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