Article ; Online: A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis.
The New England journal of medicine
2023 Volume 388, Issue 20, Page(s) 1853–1862
Abstract: Background: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with ... ...
| Abstract | Background: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with autoimmune or autoinflammatory diseases. Methods: In this phase 2a, double-blind, randomized, placebo-controlled trial, we assigned, in a 2:1:1 ratio, adult patients with moderate-to-severe rheumatoid arthritis who had had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary outcome was the change from baseline to week 12 in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP). The DAS28-CRP ranges from 0 to 9.4, with higher scores indicating more severe disease. The primary comparison was between the 700-mg group and the placebo group. Secondary outcomes included the percentages of patients with American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses - defined as improvements from baseline of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints and in at least three of five important domains - at week 12. Results: At week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], -2.09±0.18 vs. -0.99±0.26; difference in change, -1.09 [95% confidence interval, -1.73 to -0.46]; P<0.001). The results of the analyses of secondary outcomes favored the 700-mg dose over placebo with respect to the ACR20 response but not with respect to the ACR50 and ACR70 responses. Adverse events were similar in the peresolimab and placebo groups. Conclusions: Peresolimab showed efficacy in a phase 2a trial in patients with rheumatoid arthritis. These results provide evidence that stimulation of the PD-1 receptor has potential efficacy in the treatment of rheumatoid arthritis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04634253.). |
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| MeSH term(s) | Adult ; Humans ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Double-Blind Method ; Drug Therapy, Combination ; Severity of Illness Index ; Treatment Outcome ; Immunoglobulin G ; Administration, Intravenous ; Programmed Cell Death 1 Receptor/agonists | |||||
| Chemical Substances | Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Immunoglobulin G ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor | |||||
| Language | English | |||||
| Publishing date | 2023-05-17 | |||||
| Publishing country | United States | |||||
| Document type | Randomized Controlled Trial ; Clinical Trial, Phase II ; Journal Article | |||||
| ZDB-ID | 207154-x | |||||
| ISSN | 1533-4406 ; 0028-4793 | |||||
| ISSN (online) | 1533-4406 | |||||
| ISSN | 0028-4793 | |||||
| DOI | 10.1056/NEJMoa2209856 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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