Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
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
_version_ 1784669356688408576
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
work_keys_str_mv AT jaynedavid phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT rovinbrad phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT myslereduardof phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT furiericharda phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT houssiaufrederica phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT trasievateodora phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT knagenhjelmjacob phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT schwetjeerik phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT chiayenlin phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT tummalaraj phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis
AT lindholmcatharina phaseiirandomisedtrialoftypeiinterferoninhibitoranifrolumabinpatientswithactivelupusnephritis