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Peresolimab's Potential in Rheumatoid Arthritis

Peresolimab is a humanized IgG1 monoclonal antibody that acts as a programmed cell death protein 1 (PD-1) agonist (stimulator). The NEJM reports that PER met its efficacy primary endpont in treating patients with active rheumatoid arthritis (RA). 

Checkpoint inhibitors, commonly target PD-1 to upregulate immune responses in difficult to treat malignancies, such as invasive melanoma. The efficacy of these agents can be offset by the development of immune-related adverse events (irAEs), including inflammatory arthritis. In this trial, peresolimab (PER) was used to stimulate PD-1 pathways to inhibit autoimmune pathways.  

This early phase 2a, double-blind, randomized, placebo-controlled trial, of 12 weeks duration, enrolled 98 adult patients with moderate-to-severe RA (who previously failed either csDMARD or b/tsDMARDs). Patients were randomized (2:1:1) to received either 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary endpoint was the week 12 change in DAS28-CRP.

At baseline, treatment groups were well matched, 84% were women, with a mean age of 52 years, a mean RA duration of 10 years, and the mean DAS28-CRP of 5.9±0.8. A total of 42% of these RA patients were biologic or targeted synthetic DMARD experienced. 

At week 12, the DAS28-CRP change significantly favored 700-mg peresolimab (−2.09±0.18) over placebo (−0.99±0.26; P<0.001). 

The ACR responses at week 12 were only significant for PER 700 mg (compared to placebo), but not significant for ACR 50, ACR70. 

ACR Response Rates at Week 12
  Placebo PER 300 PER 700
ACR20 42% 44% 71%
ACR50 21% 20% 39%
ACR70 17% 4% 20%

PER 700 was also not beneficial with regard to patient’s global assessment of disease activity SF-36 (mental and physical components).

Adverse events (infrequent; mild to moderate) were similar in the peresolimab and placebo groups. There was only one serious AE (PER 700). 

These preliminary results from a short phase 2a trial encourage the concept that PD-1 receptor stimulation may benefit patients with active RA. 


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The author has no conflicts of interest to disclose related to this subject