A PHASE 2 TRIAL OF PERESOLIMAB FOR ADULTS WITH RHEUMATOID ARTHRITIS.
Authors: Paul Emery et al.
Peresolimab is a monoclonal antibody that binds the PD-1 inhibitory receptor. The ‘Programmed Cell Death-1 (PD-1) receptor is a checkpoint protein on T-lymphocytes that plays an immunoregulatory role by reducing T cell activation, which is also targeted by certain oncology drugs (checkpoint inhibitors that block PD-1 activate T-cells). On the contrary, Peresolimab stimulates PD-1 and thus suppresses T-cell activation.
In this Phase 2, placebo-controlled, double-blind, randomized trial 101 RA patients received either a monthly dose of intravenous peresolimab or a placebo. Patients randomized to peresolimab had significantly greater improvements in disease activity at week 12 and 24 (DAS28-CRP improvement around -2.0, compared to -1.0 in the placebo arm). Interestingly, peresolimab had similar incident safety events than placebo.
The mechanism of action of this new medication is interesting for rheumatologists. So, just like another current bDMARDs for the treatment of RA (abatacept), Peresolimab has an inverse mechanism action to some Immune Checkpoint Inhibitors used by oncologist. Whether this is a safe option remains to be seen in longer term trials, but the mechanism of action is appealing in that it may induce an immune tolerance against some arthritogenic antigens.