Stimulating PD-1 Medication Shows Promise Treating Rheumatoid Arthritis

A treatment specifically targeting programmed cell death protein 1 (PD-1) could be an effective tool in treating patients with rheumatoid arthritis.

A team, led by Jay Tuttle, Eli Lilly and Company, investigated whether peresolimab binding to programmed cell death protein 1, a checkpoint inhibitory receptor, stimulates physiological immune inhibitory pathways to restore immune homeostasis.

The data was presented as a late-breaking abstract during the 2022 American College of Rheumatology Convergence Meeting in Philadelphia.

The Treatment

Peresolimab, a humanized immunoglobulin G1 monoclonal antibody, works by stimulating human programmed cell death protein 1.

In the phase 2a, placebo-controlled, double-blind, randomized clinical trial, the investigators examined 101 adult patients with moderately to severely active rheumatoid arthritis who did not adequately respond to prior disease modifying drugs, either convention (csDMARDs), biologic (bDMARDs) or synthetic (tsDMARDS).

The patients were treated with peresolimab 700 mg (n = 49), peresolimab 300 mg (n = 25), or placebo (n = 24) every 4 weeks. The final analysis included 98 participants who received at least 1 dose of the study drug.

Baseline demographics and disease activity was similar between the 3 groups.

The mean age at baseline of the patient population was 51.7 years and 83.7% of patients were female. In addition, the mean duration of rheumatoid arthritis was 10 years and the mean DAS28-CRP score was 5.9 at baseline.

Efficacy and Safety

The investigators evaluated and compared the efficacy and safety of peresolimab with placebo using a mixed effects model for repeated measures (MMRM) and a logistic regression model for continuous and binary endpoints, respectively.

The study represented a novel approach for this patient population.

Overall, the investigators met the primary endpoint of a significantly greater improvement in DAS28-CRP scores in the trial drug group compared to placebo at both test doses from baseline to week 12 (700 mg, P <0.001; 300 mg, P = 0.017).

The treatment also resulted in significant improvements in CDAI scores (300 mg, P = 0.008; 700 mg, P <0.001). This was also true for the group treated with placebo.

There were also a significantly greater proportion of the peresolimab 700 mg group who achieved ACR20 (P <0.05) compared to participants treated with placebo by Week 12.

Extending the analysis further, the investigators found the efficacy was maintained at week 24 in patients who achieved CDAI low disease activity at week 14.

For safety, the trial drug showed a positive safety and tolerability profile that supports further clinical evaluations in patients with immunologic diseases.

“These clinical data represent the first meaningful evidence that stimulating the PD-1 receptor has the potential to treat RA,” the authors wrote. “Peresolimab was superior to placebo at Week 12 for several key endpoints. Safety events were similar between treatment groups. Future studies will continue evaluating peresolimab as treatment for RA, and for other autoimmune diseases.”

The study, “A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis,” was published online by ACR.