Phase 2a Trial Showed Peresolimab Reduced Joint Swelling, Tenderness in Patients With Rheumatoid Arthritis


This is the first clinical evidence to show that stimulating the programmed cell death protein 1 (PD1) inhibitory pathway is beneficial for rheumatologic disease.

Peresolimab (Lilly) may be safe and effective for adult patients with refractory rheumatoid arthritis (RA), according to the results of a phase 2a study (NCT04634253) published in The New England Journal of Medicine. In the study, peresolimab met the primary efficacy endpoint of improving inflammatory C-reactive protein levels.

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“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," said Ajay Nirula, MD, PhD, study senior author and senior vice president, Immunology at Lilly, in a recent press release.

The primary comparison was between peresolimab 700 mg and placebo, and the primary endpoint was change in Disease Activity Score (28 joints) based on the C-reactive protein level (DAS28-CRP) from baseline to week 12, which peresolimab (700 mg) achieved at a rate greater than placebo. In addition, peresolimab at 700 mg performed better than placebo at decreasing the numbers of tender and swollen joints by at least 20% in most (3 of 5) important domains, according to American College of Rheumatology (ACR) criteria. However, peresolimab was not superior to placebo at improving the number of tender and swollen joints by 50% and 70% (ACR50 and ACR70), respectively, from baseline to 12 weeks.

Investigators evaluated peresolimab in a phase 2a, double-blind, randomized, placebo-controlled trial, where they compared intravenous injection of peresolimab 700 mg, peresolimab 300 mg, or placebo once every 4 weeks in adult patients with moderate-to-severe RA treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic DMARDS (bDMARDS), or targeted synthetic DMARDs and had unacceptable adverse effects (AEs), inadequate response, or loss of response to treatment.

AEs were similar between the treatment and control arms. The most common AEs were infections, infestations, skin, and subcutaneous tissue disorders. There was 1 serious AE of hypothyroidism, but the patient did not discontinue treatment.

RA is a rheumatologic and systemic autoimmune disease characterized by inflammation and progressive joint deterioration. csDMARDs are the current standard of care (SoC), but most do not help patients to achieve maintenance goals. Peresolimab is an investigational humanized immunoglobulin G1 (IgG1) monoclonal antibody that stimulates PD1 to inhibit overactive immune pathways and restore homeostasis.

Rheumatic diseases have an unmet need for new treatment options, and refractory and biologic-experienced patients have an especially high need. The results of this trial support continued clinical evaluation for rheumatologic diseases. Currently, the phase 2b RESOLUTION-1 trial (NCT05516758) is evaluating peresolimab for adults with moderate-to-severe RA.

"These early data for peresolimab in RA reflect our commitment to develop first-in-class therapeutic options for patients," Nirula said in the press release.


Lilly. Lilly's peresolimab Phase 2a rheumatoid arthritis trial published in The New England Journal of Medicine. News Release. May 18, 2023. Accessed on May 24, 2023.

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