Upadacitinib for ulcerative colitis

Abstract

The medical management of inflammatory bowel disease (IBD) has been evolving at an exponential pace over the past decade, moving from the availability of only tumour necrosis factor-α inhibitors (anti-TNFα) in 1998, to the present where biologics or small molecules targeting at least five distinct mechanisms are available. In The Lancet, Silvio Danese and colleagues 1 Danese S Vermeire S Zhou W et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022; (published online May 26.)https://doi.org/10.1016/S0140-6736(22)00581-5 Summary Full Text Full Text PDF Scopus (7) Google Scholar report the results of induction and maintenance trials for upadacitinib, a selective inhibitor of the Janus kinase 1 (JAK1) enzyme, within the broader JAK enzyme family. These phase 3 trials randomly assigned patients with moderate-to-severely active ulcerative colitis to upadacitinib 45 mg orally daily (first induction study: n=319, 121 [38%] women, median age 43·0 [IQR 23·0]; second induction study: n=341, 127 [32%] women, median age 40·0 [24·0]) or placebo for 8 weeks (first induction study: n=154, 57 [37%] women, median age 44·5 [23·0]; second induction study: n=174, 67 [39%] women, median age 42·0 [24·0]). Responders were re-randomly assigned to maintenance doses of upadacitinib 15 mg (n=148, 53 [36%] women, median age 40·0 [22·0]) or 30 mg (n=154, 68 [42%] women, median age 41·0 [7·0]) orally daily or placebo (n=149, 64 [43%] women, median age 40·0 [21·0]) for an additional 52 weeks. The primary endpoint was clinical remission at 8 weeks (inductions studies) and 52 weeks (maintenance study), with key secondary endpoints of endoscopic remission, clinical response, and histological–endoscopic mucosal improvement. In the two induction studies, patients receiving upadacitinib were significantly more likely to attain clinical remission (26% and 34%) compared with placebo (5% and 4%, respectively). Similarly, during maintenance, there were higher rates of clinical remission after 52 weeks with both the 15 mg (42%) and 30 mg (52%) of upadacitinib compared with placebo (12%). Based on these results, upadacitinib was approved for treatment of ulcerative colitis by the US Food and Drug Administration in March, 2022. 2 AbbVieRINVOQ® (upadacitinib) receives FDA approval for the treatment of adults with moderately to severely active ulcerative colitis. https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-receives-fda-approval-for-treatment-adults-with-moderately-to-severely-active-ulcerative-colitis.htmDate: March 16, 2022 Date accessed: April 7, 2022 Google Scholar Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trialsUpadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis. Full-Text PDF