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At the 12-week mark, the change from baseline in the DAS28-CRP was significantly greater in patients with rheumatoid arthritis receiving 700 mg peresolimab when compared with the placebo group.
Results from a recent phase 2a trial in patients with rheumatoid arthritis (RA), peresolimab treatment demonstrated efficacy as well as similar adverse events rates between the treatment and placebo arms, according to a study published in The New England Journal of Medicine.1
Investigators noted that findings provide evidence that stimulation of the programmed cell death protein 1 (PD-1) receptor may have potential efficacy in the treatment of RA. Data were first presented as a late-breaking abstract at the American College of Rheumatology (ACR) Convergence in 2022.
Peresolimab, a humanized IgG1 monoclonal antibody designed to stimulate the endogenous PD-1 inhibitory pathway, may be a novel approach to treating patients with autoimmune or autoinflammatory diseases, particularly in patients with refractory RA.
"Our ultimate objective in treating immunologic conditions is to achieve not only symptom reduction, but to also induce immune homeostasis and achieve longstanding resolution of disease," wrote Ajay Nirula, MD, PhD, lead investigator and senior vice president, Immunology at Lilly. "These early data for peresolimab in RA reflect our commitment to develop first-in-class therapeutic options for patients."2
Investigators assigned patients with moderate-to-severe RA who had an inadequate response to, loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic DMARDs (bDMARDs), or targeted synthetic DMARDs (tsDMARDs), in a 2:1:1 ratio to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks in this phase 2a, double-blind, randomized, placebo-controlled trial.
The primary endpoint was the change in the Disease Activity Score for 28 joints passed on the C-reactive protein level (DAS28-CRP) from baseline to week 12. The DAS28-CRP ranges from 0 to 9.4; higher scores are indicative of more severe disease. The main comparison was between the 700 mg cohort and the placebo cohort.
The secondary endpoints included the proportion of patient with ACR response criteria, defined as improvements from baseline of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) in the numbers of tender and swollen joints in at least 3 of 5 primary domains at week 12.
At the 12-week mark, the change from baseline in the DAS28-CRP was significantly greater in patients receiving 700 mg peresolimab when compared with the placebo group (least-squares mean change [±SE], −2.09± .18 vs −.99±0.26; difference in change, −1.09 [95% confidence interval (CI), −1.73 to −.46]; P <.001).
Regarding secondary outcomes, the analyses favored the 700 mg dose when compared with placebo regarding the ACR20 response; however, results were not mirrored with the ACR50 and ACR70 responses.
Improvements were also observed in the Clinical Disease Activity Index (CDAI) in patients in both peresolimab cohorts when compared with placebo. Further, low disease activity was maintained through week 24 in most patients who were able to achieve CDAI low disease activity at week 14.
Adverse events were comparable between treatment and placebo groups. Treatment-emergent adverse events (TEAEs) were categorized as either mild or moderate in severity, with the most commonly reported events being infections and infestations, as well as skin and subcutaneous tissue disorders. One serious event was reported during the treatment period (worsening of hypothyroidism, 700 mg); however, it did not result in treatment discontinuation. No malignancies and no deaths were reported.
“These data represent the first clinical evidence that stimulating the endogenous PD-1 inhibitory pathway could be an effective approach to treat rheumatologic disease,” investigators concluded. “Peresolimab showed meaningful results in refractory RA patients.”