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Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis
OBJECTIVE: To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. METHODS: This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic reg...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921596/ https://www.ncbi.nlm.nih.gov/pubmed/35144924 http://dx.doi.org/10.1136/annrheumdis-2021-221478 |
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author | Jayne, David Rovin, Brad Mysler, Eduardo F Furie, Richard A Houssiau, Frederic A Trasieva, Teodora Knagenhjelm, Jacob Schwetje, Erik Chia, Yen Lin Tummala, Raj Lindholm, Catharina |
author_facet | Jayne, David Rovin, Brad Mysler, Eduardo F Furie, Richard A Houssiau, Frederic A Trasieva, Teodora Knagenhjelm, Jacob Schwetje, Erik Chia, Yen Lin Tummala, Raj Lindholm, Catharina |
author_sort | Jayne, David |
collection | PubMed |
description | OBJECTIVE: To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. METHODS: This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), intensified regimen (IR, 900 mg ×3, 300 mg thereafter) or placebo, alongside standard therapy (oral glucocorticoids, mycophenolate mofetil). The primary endpoint was change in baseline 24-hour urine protein–creatinine ratio (UPCR) at week (W) 52 for combined anifrolumab versus placebo groups. The secondary endpoint was complete renal response (CRR) at W52. Exploratory endpoints included more stringent CRR definitions and sustained glucocorticoid reductions (≤7.5 mg/day, W24–52). Safety was analysed descriptively. RESULTS: Patients received anifrolumab BR (n=45), IR (n=51), or placebo (n=49). At W52, 24-hour UPCR improved by 69% and 70% for combined anifrolumab and placebo groups, respectively (geometric mean ratio=1.03; 95% CI 0.62 to 1.71; p=0.905). Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which provided suboptimal exposure. Numerically more patients treated with anifrolumab IR vs placebo attained CRR (45.5% vs 31.1%), CRR with UPCR ≤0.5 mg/mg (40.9% vs 26.7%), CRR with inactive urinary sediment (40.9% vs 13.3%) and sustained glucocorticoid reductions (55.6% vs 33.3%). Incidence of herpes zoster was higher with combined anifrolumab vs placebo (16.7% vs 8.2%). Incidence of serious adverse events was similar across groups. CONCLUSION: Although the primary endpoint was not met, anifrolumab IR was associated with numerical improvements over placebo across endpoints, including CRR, in patients with active lupus nephritis. TRIAL REGISTRATION NUMBER: NCT02547922. |
format | Online Article Text |
id | pubmed-8921596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-89215962022-03-25 Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis Jayne, David Rovin, Brad Mysler, Eduardo F Furie, Richard A Houssiau, Frederic A Trasieva, Teodora Knagenhjelm, Jacob Schwetje, Erik Chia, Yen Lin Tummala, Raj Lindholm, Catharina Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVE: To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. METHODS: This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), intensified regimen (IR, 900 mg ×3, 300 mg thereafter) or placebo, alongside standard therapy (oral glucocorticoids, mycophenolate mofetil). The primary endpoint was change in baseline 24-hour urine protein–creatinine ratio (UPCR) at week (W) 52 for combined anifrolumab versus placebo groups. The secondary endpoint was complete renal response (CRR) at W52. Exploratory endpoints included more stringent CRR definitions and sustained glucocorticoid reductions (≤7.5 mg/day, W24–52). Safety was analysed descriptively. RESULTS: Patients received anifrolumab BR (n=45), IR (n=51), or placebo (n=49). At W52, 24-hour UPCR improved by 69% and 70% for combined anifrolumab and placebo groups, respectively (geometric mean ratio=1.03; 95% CI 0.62 to 1.71; p=0.905). Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which provided suboptimal exposure. Numerically more patients treated with anifrolumab IR vs placebo attained CRR (45.5% vs 31.1%), CRR with UPCR ≤0.5 mg/mg (40.9% vs 26.7%), CRR with inactive urinary sediment (40.9% vs 13.3%) and sustained glucocorticoid reductions (55.6% vs 33.3%). Incidence of herpes zoster was higher with combined anifrolumab vs placebo (16.7% vs 8.2%). Incidence of serious adverse events was similar across groups. CONCLUSION: Although the primary endpoint was not met, anifrolumab IR was associated with numerical improvements over placebo across endpoints, including CRR, in patients with active lupus nephritis. TRIAL REGISTRATION NUMBER: NCT02547922. BMJ Publishing Group 2022-04 2022-02-10 /pmc/articles/PMC8921596/ /pubmed/35144924 http://dx.doi.org/10.1136/annrheumdis-2021-221478 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 Jayne, David Rovin, Brad Mysler, Eduardo F Furie, Richard A Houssiau, Frederic A Trasieva, Teodora Knagenhjelm, Jacob Schwetje, Erik Chia, Yen Lin Tummala, Raj Lindholm, Catharina Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title | Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title_full | Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title_fullStr | Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title_full_unstemmed | Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title_short | Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis |
title_sort | phase ii randomised trial of type i interferon inhibitor anifrolumab in patients with active lupus nephritis |
topic | Systemic Lupus Erythematosus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921596/ https://www.ncbi.nlm.nih.gov/pubmed/35144924 http://dx.doi.org/10.1136/annrheumdis-2021-221478 |
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