In a letter to the editor published by Nepal et al in The New England Journal of Medicine, investigators expressed concern over a recent phase IIa trial, published by Tuttle et al in the journal, which examined PD-1 receptor stimulation with peresolimab in patients with rheumatoid arthritis. The investigators stressed that the new approach may increase the risk of cancer in this patient population—and that the trial size was not large enough and the study period was not long enough to fully understand the potential hazards of PD-1 stimulation. They cited a former trial from 2012 in which a similar risk was ignored in patients receiving tofacitinib and urged regulatory agencies to take action to prevent the same events from occurring with the investigation of peresolimab. The investigators concluded that if peresolimab is approved following phase III trials, postmarketing trials and safety warnings may be essential for patient safety.