Upadacitinib outperformed placebo in inducing and maintaining endoscopic response and remission in Crohn’s disease, regardless of previous biologic failure.
Upadacitinib showed superior efficacy compared with placebo in two phase 3, multicenter, induction trials (U-EXCEL and U-EXCEED) and one maintenance trial (U-ENDURE). At DDW 2023, Brian Feagan, MD, presented the results of endoscopic outcomes in participants with moderate to severe Crohn’s disease receiving upadacitinib treatment with or without a history of biologic failure. The results were based on a sub-analysis using pooled data from these three trials.
Participants were administered upadacitinib 45 mg once daily or placebo for 12 weeks. Responders were subsequently re-randomized to receive either upadacitinib, 30 mg or 15 mg, or placebo, for an additional 52 weeks. Key endpoints were the endoscopic response and remission measured at weeks 12 and 52.
At the outset, participants’ demographics and disease characteristics were largely similar across the treatment groups. About two-thirds of participants had a history of biologic failure.
At week 12, 52% of biologic-naïve participants and 35.7% of participants with prior biologic failure demonstrated endoscopic response with upadacitinib, compared with 16.2% and 5.3%, respectively, with placebo. Endoscopic remission was also higher with upadacitinib, with 36% of biologic-naïve participants and 19.6% of those with prior biologic failure showing remission, compared with 10.1% and 2.8%, respectively, with placebo.
A dose-dependent response emerged in the maintenance phase. For participants with biologic failure history, a higher endoscopic response was noted with upadacitinib 15 mg compared with placebo at week 52 (delta 19.2; 95% CI, 11.0-27.4). However, differences from placebo were even higher with the 30 mg dose (delta 34.9; 95% CI, 25.8-44.1). Results for endoscopic remission showed the same trend for the 30-mg (delta 24.4; 95% CI, 16.3-32.6) and 15-mg (delta 13.8; 95% CI, 6.8-20.8) doses, compared with placebo. In biologic-naïve participants, the difference was not so evident.
No new safety risks arose. A few participants experienced sporadic liver enzyme changes, creatine phosphokinase alterations, and zoster events, but the frequency was not significant enough to be of concern.
Upadacitinib proved to be a beneficial treatment for moderate to severe CD, promoting endoscopic response and remission, regardless of prior biologic failure. It was well tolerated among participants, with a consistent safety profile, highlighting it as a promising option for CD treatment.
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