Peresolimab beneficial for patients with rheumatoid arthritis, compared with placebo: NEJM

In a recent study, Jay Tuttle and team have reported encouraging results from a phase 2a clinical trial of Peresolimab, a humanized IgG1 monoclonal antibody designed to target the programmed cell death protein 1 (PD-1) inhibitory pathway. The trial investigated Peresolimab's potential as a novel treatment for patients suffering from moderate-to-severe rheumatoid arthritis, particularly those who had not responded adequately to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic and targeted synthetic DMARDs. The findings were published in New England Journal of Medicine.

The double-blind, randomized, and placebo-controlled trial involved adult patients with rheumatoid arthritis who were assigned in a 2:1:1 ratio to receive either 700 mg of Peresolimab, 300 mg of Peresolimab, or placebo intravenously every 4 weeks. The primary endpoint of the study was the change in Disease Activity Score for 28 joints based on C-reactive protein levels (DAS28-CRP) at week 12. The DAS28-CRP measures disease severity, with higher scores indicating more severe symptoms.

The results were highly promising. At week 12, the 700-mg Peresolimab group exhibited a significantly greater change in DAS28-CRP from baseline compared to 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). This significant improvement indicates that Peresolimab effectively reduced disease activity in patients with rheumatoid arthritis.

Secondary outcomes of the trial included measuring the percentages of patients with American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses at week 12. The ACR responses refer to the degree of improvement in tender and swollen joints and other important domains. While the ACR20 response was favorable in the 700-mg Peresolimab group compared to the placebo group, the differences in ACR50 and ACR70 responses did not reach statistical significance.

Importantly, the safety profile of Peresolimab was similar to that of the placebo, with no significant differences observed in adverse events between the groups. This safety outcome is crucial for future developments in the treatment's clinical application.

The positive results from this phase 2a trial offer compelling evidence that stimulating the PD-1 inhibitory pathway through Peresolimab has the potential to be an effective treatment option for rheumatoid arthritis.

Source:

Tuttle, J., Drescher, E., Simón-Campos, J. A., Emery, P., Greenwald, M., Kivitz, A., Rha, H., Yachi, P., Kiley, C., & Nirula, A. (2023). A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis. In New England Journal of Medicine (Vol. 388, Issue 20, pp. 1853–1862). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2209856