Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-wUpadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme.In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integrated safety reviewed. Upadacitinib 15 mg demonstrated a favourable benefit–risk profile both in combination with csDMARDs/MTX or as a monotherapy. This favourable profile was observed across a range of patients with moderately-to-severely active RA and included patients both naïve to MTX or with an inadequate response/intolerance to csDMARDs or bDMARDs. Risks observed with upadacitinib 15 mg were similar to those reported for other JAK inhibitors and, with the exception of herpes zoster and CPK elevations, the safety profile of UPA was similar to that observed with adalimumab. While the safety of upadacitinib continues to be monitored, overall conclusions from this review indicate that upadacitinib fulfils an unmet medical need for patients with RA.