medwireNews: Peresolimab, a PD-1 receptor agonist, may represent a promising approach to treating rheumatoid arthritis (RA), with an “encouraging” safety profile, suggests research reported at the ACR Convergence 2022 in Philadelphia, Pennsylvania, USA.
The phase 2 study included 98 adults with moderate-to-severe RA, objective evidence of synovitis, and an inadequate response, loss of response, or intolerance to at least one conventional or biologic/targeted synthetic DMARD. In all, 29 participants were randomly assigned to receive peresolimab 300 mg every 4 weeks, 49 were given peresolimab 700 mg every 4 weeks, and 24 received placebo.
Paul Emery (University of Leeds, UK) told delegates that both doses of peresolimab showed significant superiority to placebo for reduction in DAS28-CRP score during the first 12-week period of the study. Specifically, the least squares mean decrease from baseline was approximately 2 points in both treatment arms and 1 point in the placebo arm.
There were also significant improvements in CDAI through week 12 with both doses of peresolimab compared with placebo, showing that “at the joint level, this drug clearly works,” said Emery. In this case, the least squares mean decrease from baseline was approximately 25 points in both peresolimab arms and 12 points in the placebo arm.
The presenter also reported that similar efficacy was seen regardless of prior exposure to DMARDs, which suggests that “peresolimab could be effective in more refractory patients.”
At week 14, patients who achieved low disease activity (CDAI ≤10) with peresolimab continued with the PD‑1 receptor agonist, and these people achieved sustained reductions in CDAI until the 24-week follow-up.
In terms of safety, overall rates of treatment-emergent adverse events (TEAEs) were similar across treatment groups, at 32.0% in the 300 mg group, 28.6% in the 700 mg group, and 37.5% in the placebo arm during weeks 0–12. The investigators found that peresolimab dose had no impact on the appearance of TEAEs and none of the patients receiving high-dose peresolimab discontinued treatment due to AEs at any stage of the study.
Emery said: “[T]hese data represent the first clinical evidence that agonism of checkpoint inhibitory receptors could be an effective approach to treat rheumatologic disease.”
And he concluded: “Future studies will continue evaluating peresolimab as treatment for RA and other autoimmune diseases.”
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ACR Convergence 2022; Philadelphia, Pennsylvania, USA: November 10–14