Crohn’s disease: Upadacitinib improves endoscopic outcomes in participants with or without previous biologic failure

Upadacitinib outperformed the placebo in inducing and maintaining both endoscopic response and remission, regardless of whether participants with moderate-to-severe Crohn’s disease (CD) had previously failed biologic therapy.

Upadacitinib showed superior efficacy compared with placebo in 2 multicentre, phase 3 induction (U-EXCEL [NCT03345849] and U-EXCEED [NCT03345836]) and 1 maintenance (U-ENDURE [NCT03345823]) trials [1]. Based on a sub-analysis using pooled data from these 3 trials, Dr Brian Feagan (Western University, Canada) presented the results of endoscopic outcomes in participants receiving upadacitinib treatment with or without a history of biologic failure.

Participants were administered upadacitinib 45 mg once daily or placebo for 12 weeks. Responders were subsequently re-randomised 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. Around 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 and 19.6% of those with prior biologic failure showing remission, against 10.1% and 2.8%, respectively, with placebo.

A dose-dependent response emerged in the maintenance phase. For participants with a history of biologic failure, 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 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 as evident.

As for safety, no new risks arose. A few participants experienced sporadic liver enzyme changes, creatine phosphokinase alterations, and herpes zoster events, but the frequency was not significant enough to be of concern.

In conclusion, 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.

1. Feagan B, et al. Upadacitinib improves endoscopic outcomes in patients with moderate to severely active Crohn’s disease irrespective of previous failure to respond to biologics or conventional therapies. Lecture 1031, DDW 2023, 6–9 May, Chicago, IL, USA.

 

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Posted on 13 June, 20238 April, 2024