CD: Induction treatment with upadacitinib successful in clinical and endoscopic ratings

Upadacitinib outperformed placebo in patients with moderate-to-severe Crohn’s disease (CD). Besides clinical remission and endoscopic response rates, steroid-free and endoscopic remissions were significantly higher on treatment with the JAK inhibitor.

Upadacitinib showed promising results compared with placebo in the phase 2 CELEST trial (NCT02365649) and has thus advanced to double-blind, phase 3 testing [1]. Prof. Jean-Frederic Colombel (Mount Sinai Hospital, NY, USA) presented the results of U-EXCEED (NCT03345836), which investigated upadacitinib as induction therapy for patients with moderately-to-severely active CD who had a preceding inadequate response to biologics.

The study randomised 495 patients 2:1 to receive either daily 45 mg upadacitinib or placebo over 12 weeks. For those patients who were on corticosteroids (34%) at baseline, tapering was initiated after 4 study weeks. The co-primary endpoints at week 12 were clinical remission and endoscopic response. Baseline measures included about 50% of men, mean age of around 38 years, and a median of 9–10 years of disease duration. In 60.8% of patients, the history showed the failure of at least 2 previous biologics, the majority of them TNF inhibitors.

The primary endpoints at week 12 were both met. Clinical remission measured by Crohn's Activity Index (CDAI) <150 was achieved by 39% on upadacitinib compared with 21% on placebo (P<0.0001). Also, significantly more patients had a ≥30% decrease in stool frequency (SF)/average daily abdominal pain score (APS): 40% versus 14% (P<0.0001 in favour of upadacitinib). Interestingly, about a third of patients in the upadacitinib group experienced a ≥100-point decrease in CDAI as early as week 2 and CDAI clinical remission at week 4. As for the endoscopic response, the threshold of a ≥50% decrease in the Simple Endoscopic Score for Crohn`s Disease (SES-CD) was present in 35% and 4% of the upadacitinib and placebo group, respectively (P<0.0001).

Of the study participants previously taking corticosteroids, significantly more individuals in the upadacitinib group reached a clinical remission measured by CDAI (34% vs 12%; P<0.0001) as well as SF/APS (37% vs 7%; P<0.0001). Endoscopic remission was seen in more patients on upadacitinib with a difference of 17% between groups.

In terms of safety, treatment-emergent adverse events were observed in 65% in the placebo and 68% in the upadacitinib group. Concerning severe and serious treatment-emergent adverse events, the rates were lower in the upadacitinib than in the placebo group (9% each, versus 12% and 10%). Most common were nasopharyngitis and headache (upadacitinib) or CD worsening and abdominal pain (placebo).

In summary, upadacitinib was found to be rapidly acting and overall superior to placebo in this study population, while being well-tolerated.

1. Colombel JF, et al. Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active Crohn's disease who failed prior biologics: results from a randomized phase 3 U-EXCEED study. Lecture 867f, Digestive Disease Week 2022, 21–24 May, San Diego, CA, USA.

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Posted on 14 June 20228 April 2024