Rapid response to upadacitinib boosts outcomes in severe Crohn’s disease

Upadacitinib, an oral selective JAK1 inhibitor, showed promising results in the treatment of moderate-to-severe active Crohn’s disease (CD) in 2 phase 3 trials. A post-hoc analysis of these studies focused on participants who exhibited early responsiveness to upadacitinib and demonstrated improved clinical and endoscopic outcomes over time.

In the U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849) studies, upadacitinib demonstrated its efficacy compared with placebo as a treatment option for participants with moderately to severely active CD. Prof. Jean-Frederic Colombel (Icahn School of Medicine at Mount Sinai, NY, USA) presented a post-hoc analysis that concentrated on participants who demonstrated early clinical improvements within the initial 15 days of treatment [1]. These early responders were monitored and evaluated for clinical and endoscopic outcomes during the 12-week induction and 52-week maintenance phases.

At week 12, early responders exhibited higher rates of stool frequency and abdominal pain score (SF/APS) clinical remission (84% vs 46%) and mucosal healing (34% vs 21%) with upadacitinib compared with the overall population. These improvements persisted through the 52-week maintenance phase, underscoring the sustained effectiveness of upadacitinib (see Figure).

Figure: Clinical outcomes for early responders and the overall population at week 52 [1]



CDAI, Crohn’s Disease Activity Index; PBO, placebo; QD, once daily; SF/APS, stool frequency and abdominal pain score; UPA, upadacitinib.

"This is quite encouraging, and we should aim to look further at the predictors of response, as those patients who are responding very well to the treatment early on are doing well at weeks 12 and 52," Prof. Colombel emphasised. The findings suggest that an early response to upadacitinib therapy could be a strong indicator of sustained improvement and effectiveness in CD. This discovery could be instrumental in identifying and categorising patients more likely to benefit from upadacitinib therapy, enabling a more personalised and effective treatment approach.

1. 
   
   1. Colombel J-F, et al. Rapid clinical response to upadacitinib therapy is associated with improved clinical and endoscopic outcomes in patients with moderate to severe Crohn’s disease. OP099, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December, 20238 April, 2024