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B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial
OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN i...
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/PMC8762029/ https://www.ncbi.nlm.nih.gov/pubmed/34615636 http://dx.doi.org/10.1136/annrheumdis-2021-220920 |
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author | Furie, Richard A Aroca, Gustavo Cascino, Matthew D Garg, Jay P Rovin, Brad H Alvarez, Analia Fragoso-Loyo, Hilda Zuta-Santillan, Elizabeth Schindler, Thomas Brunetta, Paul Looney, Cary M Hassan, Imran Malvar, Ana |
author_facet | Furie, Richard A Aroca, Gustavo Cascino, Matthew D Garg, Jay P Rovin, Brad H Alvarez, Analia Fragoso-Loyo, Hilda Zuta-Santillan, Elizabeth Schindler, Thomas Brunetta, Paul Looney, Cary M Hassan, Imran Malvar, Ana |
author_sort | Furie, Richard A |
collection | PubMed |
description | OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. METHODS: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. RESULTS: A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI −3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. CONCLUSIONS: Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified. TRIAL REGISTRATION NUMBER: NCT02550652. |
format | Online Article Text |
id | pubmed-8762029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-87620292022-01-26 B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Furie, Richard A Aroca, Gustavo Cascino, Matthew D Garg, Jay P Rovin, Brad H Alvarez, Analia Fragoso-Loyo, Hilda Zuta-Santillan, Elizabeth Schindler, Thomas Brunetta, Paul Looney, Cary M Hassan, Imran Malvar, Ana Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. METHODS: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. RESULTS: A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI −3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. CONCLUSIONS: Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified. TRIAL REGISTRATION NUMBER: NCT02550652. BMJ Publishing Group 2022-01 2021-10-06 /pmc/articles/PMC8762029/ /pubmed/34615636 http://dx.doi.org/10.1136/annrheumdis-2021-220920 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 Furie, Richard A Aroca, Gustavo Cascino, Matthew D Garg, Jay P Rovin, Brad H Alvarez, Analia Fragoso-Loyo, Hilda Zuta-Santillan, Elizabeth Schindler, Thomas Brunetta, Paul Looney, Cary M Hassan, Imran Malvar, Ana B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title | B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title_full | B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title_fullStr | B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title_full_unstemmed | B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title_short | B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
title_sort | b-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial |
topic | Systemic Lupus Erythematosus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762029/ https://www.ncbi.nlm.nih.gov/pubmed/34615636 http://dx.doi.org/10.1136/annrheumdis-2021-220920 |
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