by Elana Gotkine

Peresolimab, a humanized immunoglobulin G1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway, is efficacious for patients with rheumatoid arthritis, according to a study published in the May 18 issue of the New England Journal of Medicine.

Jay Tuttle, Ph.D., from Eli Lilly in San Diego, and colleagues conducted a phase 2a trial involving adults with moderate-to-severe rheumatoid arthritis who 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. Participants were randomly assigned to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every four weeks in a 2:1:1 ratio.

The researchers found that the change from baseline in the Disease Activity Score for 28 joints based on the C-reactive protein level was significantly greater in the 700-mg peresolimab group versus the placebo group at week 12 (least-squares mean change, −2.09 ± 0.18 versus −0.99 ± 0.26). With response to the percentages of patients with American College of Rheumatology 20 (ACR20) response, but not the ACR50 and ACR70 responses, the results favored the 700-mg dose over placebo.

"Peresolimab is a humanized monoclonal antibody designed to stimulate PD-1, with the goal of suppressing T-cell activation," write the authors of an accompanying editorial. "This novel approach provides an exciting therapeutic mechanism for the treatment of rheumatoid arthritis and potentially other autoimmune diseases in which antigen-activated lymphocytes play a pathogenic role."

The study was funded by Eli Lilly, the manufacturer of peresolimab.

More information: Jay Tuttle et al, A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2209856

Ellen M. Gravallese et al, Reinforcing the Checkpoint in Rheumatoid Arthritis, New England Journal of Medicine (2023). DOI: 10.1056/NEJMe2300734

Journal information: New England Journal of Medicine 

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