Induction therapy with upadacitinib was associated with improved outcomes compared with placebo among patients with moderate to severe Crohn disease (CD), according to study results presented at the American College of Gastroenterology (ACG) 2022 Annual Meeting, held from October 21 to 26, 2022, in Charlotte, North Carolina, and virtually.

The U-EXCEL study was a randomized trial of upadacitinib. Patients with moderate to severe CD were randomly assigned 2:1 to receive 45mg daily upadacitinib (n=350) or placebo (n=176) for 12 weeks. The primary endpoints were clinical remission, defined as Clinical Disease Activity Index (CDAI) less than 150 (sites in United States) or stool frequency (SF) less than or equal to 2.8 and abdominal pain score (APS) less than or equal to 1.0 (sites in European Union), and endoscopic response, defined as Simple Endoscopic Score for CD (SES-CD) reduction of greater than 50% from baseline or at least a 2-point reduction if SES-CD=4 at baseline. The secondary endpoint of endoscopic remission was defined as SES-CD less than or equal to 4, less than or equal to a 2-point reduction from baseline, and no subscore greater than 1.

The patient cohorts were well-balanced at baseline, and, overall, 45.4% had a history of biologic therapy failure.

At week 12, upadacitinib was favored for clinical remission defined using CDAI (mean difference [MD], 20.8%; 95% CI, 12.7%-28.8%; P <.0001), clinical remission defined using SF/APS (MD, 28.7%; 95% CI, 20.9%-36.4%; P <.0001), and endoscopic response (MD, 33.0%; 95% CI, 26.2%-39.9%; P <.0001) compared with placebo.

The secondary endpoints of CDAI clinical remission at week 4 (MD, 10.8%; 95% CI, 2.9%-18.6%; P <.01), SF/APS remission at week 4 (MD, 21.2%; 95% CI, 14.3%-28.2%; P <.0001), corticosteroid-free CDAI clinical remission at week 12 (MD, 27.7%; 95% CI, 15.7%-39.8%; P <.0001), corticosteroid-free SF/APS clinical remission at week 12 (MD, 32.6%; 95% CI, 21.5%-43.7%; P <.0001), and endoscopic remission at week 12 (MD, 21.8%; 95% CI, 15.8%-27.8%; <.0001) were achieved by more upadacitinib recipients compared with placebo recipients.

The most frequently reported adverse events were acne and anemia among the upadacitinib cohort. Serious infections were reported by 1.1% of upadacitinib and 1.7% of placebo groups. Only upadacitinib recipients reported herpes zoster infections (2.9%).

This study may have been limited by the differing definitions of clinical remission depending on the study site. “UPA45 [upadacitinib] was well tolerated, with no new safety risks and a safety profile comparable to previous UPA [upadacitinib] studies,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Loffus EV, Colombel J-F, Lacerda AP, et al. Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active Crohn’s disease: results from a randomized Phase 3 U-EXCEL study. Abstract presented at: ACG 2022 Annual Meeting; October 21-26, 2022; Charlotte, NC. Abstract C0375.

This article originally appeared on Gastroenterology Advisor.