Peresolimab Promising for RA

ACR CONVERGENCE 2022—Peresolimab (LY3462817) is a humanized anti-immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1), a checkpoint inhibitory receptor. In a double-blind, placebo-controlled study, Tuttle et al. hypothesized that peresolimab binding to PD-1 may stimulate physiological immune inhibitory pathways to restore immune homeostasis, resulting in a new way to treat patients with autoimmune or autoinflammatory diseases. The data from this research were presented during ACR Convergence 2022.¹

Methods

This randomized clinical trial (NCT04634253) evaluated the safety and efficacy of peresolimab for treating adults with moderate to severe active rheumatoid arthritis (RA).² To be included in the study, patients (N=101) had to have had a prior inadequate response to either conventional systemic disease-modifying anti-rheumatic drugs (DMARDs), biologic DMARDs or synthetic DMARDs.

Patients were randomized in a 2:1:1 ratio to receive an intravenous infusion of 700 mg of peresolimab (n=49), 300 mg of peresolimab (n=25) or a matched placebo infusion (n=24; 0.9% sodium chloride solution) every four weeks. The study’s primary end point at week 12 was a significant improvement from baseline in the Disease Activity Score 28 joint count C‐reactive protein (DAS28-CRP) score.

Treatment comparisons were made using a mixed effects model for repeated measures and a logistic regression model for continuous and binary end points, respectively. Nominal P values were reported. Missing data for binary end points were imputed as non-response. The study also assessed patients’ ACR20 response rates and Clinical Disease Activity Index (CDAI) scores.

The Results

Baseline demographics were similar among the three treatment groups. Most study participants were women (83.7%), with a mean age of 51.7 years (standard deviation [SD] 12.6). At the beginning of the study, the mean duration of RA was 10 years (SD 8) and the mean DAS28-CRP was 5.9 (SD 0.85). Ninety-eight patients received at least one dose of peresolimab and were included in the analysis.

The study met its primary end point. From baseline to week 12, patients treated with peresolimab had a significantly greater improvement in DAS28-CRP scores than those who received placebo (700 mg [P<0.001] and 300 mg [P=0.017]). These patients also had significantly improved CDAI scores compared with those who received placebo (P<0.01 and P<0.001). Patients who achieved a low CDAI at week 14 maintained that improvement through week 24. Also by week 12, a greater percentage of patients treated with peresolimab achieved an ACR20 response (P<0.05) than patients who received placebo. 

No serious adverse events were reported. Peresolimab had a good safety and tolerability profile.

Conclusion

The results of this study show that stimulating the PD-1 receptor with peresolimab has the potential to treat RA. Further research may increase the number of pharmaceutical agents available to manage autoimmune diseases.

References

1. Tuttle J, Drescher E, Simón-Campos J, et al. A phase 2 trial of peresolimab for adults with rheumatoid arthritis [abstract: L03]. Arthritis Rheumatol. 2022 Oct; 74(suppl 9).
2. A study of LY3462817 in participants with rheumatoid arthritis (NCT04634253). ClinicalTrials.gov. 2023 Feb 1.