Peresolimab's Potential in Rheumatoid Arthritis Save
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.
|Placebo||PER 300||PER 700|
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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