Peresolimab shows promise for rheumatoid arthritis in Phase 2a trial
In a significant breakthrough, a phase 2a clinical trial has shown promising results for Peresolimab, a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway in patients with autoimmune or autoinflammatory diseases, with a focus on rheumatoid arthritis.
The double-blind, randomized, placebo-controlled trial involving adult patients who had experienced an inadequate response to, a loss of response to, or unacceptable side effects from conventional synthetic disease-modifying antirheumatic drugs (DMARDs), as well as biologic or targeted synthetic DMARDs. Participants were assigned in a 2:1:1 ratio to receive either 700 mg of peresolimab, 300 mg of peresolimab, or a placebo intravenously once every 4 weeks.
The primary outcome measure of the study was the change in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP) from baseline to week 12. The DAS28-CRP scale ranges from 0 to 9.4, with higher scores indicating more severe disease. Secondary outcomes included the percentages of patients achieving American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses at week 12. These responses were defined as improvements of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints, as well as in at least 3 of 5 important domains.
The results revealed a significant improvement in the DAS28-CRP scores among patients who received the 700 mg dose of peresolimab compared to the placebo group. While the analysis of secondary outcomes favored the 700 mg dose in terms of the ACR20 response, there were no significant differences observed between the groups for the ACR50 and ACR70 responses., Adverse events were similar in both the peresolimab and placebo groups.
Reference
Tuttle J, Drescher E, Simón-Campos JA, et al. A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis. N Engl J Med. 2023;388(20):1853-1862. doi: 10.1056/NEJMoa2209856. PMID: 37195941.
