B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial
| Autor: | J Garg, Analia Alvarez, Elizabeth Zuta-Santillan, Paul Brunetta, Ana Malvar, Cary M. Looney, Brad H. Rovin, Thomas Schindler, Richard Furie, Matthew D Cascino, Imran Hassan, Gustavo Aroca, Hilda Fragoso-Loyo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Immunology Lupus nephritis Placebo-controlled study Antibodies Monoclonal Humanized Placebo Systemic Lupus Erythematosus Gastroenterology General Biochemistry Genetics and Molecular Biology Placebos Young Adult chemistry.chemical_compound Antineoplastic Agents Immunological rituximab Double-Blind Method Rheumatology Adrenal Cortex Hormones Obinutuzumab Internal medicine Clinical endpoint Humans Immunology and Allergy Medicine Enzyme Inhibitors Adverse effect lupus nephritis B-Lymphocytes business.industry Mycophenolic Acid systemic medicine.disease Treatment Outcome chemistry Drug Therapy Combination Female Rituximab Ocrelizumab business lupus erythematosus Glomerular Filtration Rate medicine.drug |
| Zdroj: | Annals of the Rheumatic Diseases |
| ISSN: | 1468-2060 0003-4967 0255-0652 |
| DOI: | 10.1136/annrheumdis-2021-220920 |
| Popis: | ObjectiveRandomised 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.MethodsPatients 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.ResultsA 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.ConclusionsImproved 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 numberNCT02550652. |
| Databáze: | OpenAIRE |
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