Highlights from

ECCO 2019

European Crohn's and Colitis Organisation's 14th congress

Copenhagen 6-9 March 2019

Upadacitinib: data from U-ACHIEVE and CELEST

Upadacitinib is an oral, selective Janus kinase 1 inhibitor. In a dose-ranging phase 2b/3 induction study, upadacitinib consistently demonstrated significant improvement in endoscopic and histological outcomes as well as mucosal healing compared with placebo in patients with moderately to severely active ulcerative colitis [1]. In moderate-to-severe Crohn’s disease, upadacitinib numerically reduced extra-intestinal manifestations [2].

Patients (n=250) with an adapted Mayo score of 5 to 9 points and centrally read endoscopy subscore of 2 to 3 were randomised to receive placebo or extended-release upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg once daily for 8 weeks. At baseline, 77.6% had used biologics before, 36% had an adapted Mayo score of >7, and 79% had an endoscopic subscore of 3. At week 8, a dose-response relationship was observed for all efficacy endpoints. The proportion of patients achieving endoscopic improvement, endoscopic remission, histological improvement, histological remission, and mucosal healing was statistically significantly higher (P<0.05) in the upadacitinib 30 mg and 45 mg groups than in the placebo group (see Table 1).

Table 1: Proportion of patients achieving efficacy endpoints at week 8 [1]

Proportion of patients achieving efficacy endpoints

****, **, , + statistically significant at 0.001, 0.01, 0.05, and 0.1 levels, respectively. QD, once daily.

In Crohn’s disease patients participating in the CELEST study, a numerical resolution in extra-intestinal manifestations (EIMs) was observed with upadacitinib, suggesting a clinical benefit induced by upadacitinib. CELEST was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study in 220 adults with moderate-to-severe Crohn’s disease and inadequate response/intolerance to immunosuppressants or TNFi. Patients were randomised to 16-week induction therapy with placebo or Crohn’s disease 3 mg, 6 mg, 12 mg, or 24 mg twice daily or 24-mg once daily. The presence of EIMs was recorded at baseline and week 16.

Out of 220 patients, 111 (50.5%) had at least 1 EIM at baseline; 31 (28%) of these had 2 or more EIMs. Patients who had at least one EIM at baseline had median (min-max) Crohn’s Disease Activity Index (CDAI) 295 (222–447), and Crohn’s Disease duration of 10.8 (0.1-44.7) years; 85 (96.6%) had failed 1 or more TNFi. The most commonly reported EIMs were peripheral and/or axial arthropathies (n=87), anaemia (n=31), and oral aphthous ulcers (n=11). At week 16, compared with placebo, a numerically greater proportion of patients achieved resolution of any EIM, classic EIMs, and arthropathy with upadacitinib 12 mg and 24 mg twice daily, and upadacitinib 24 mg once daily doses (see Table 2).

Table 2: Proportion of patients achieving resolution of any EIMs, and arthropathy at week 16 [2]

Proportion of patients achieving resolution of any EIMs

Data are reported in the modified intent-to-treat population. Resolution of extra-intestinal manifestations (EIMs) was defined as zero EIMs at Week 16. Resolution of classic EIMs was defined as zero peripheral arthropathy, axial arthropathy, episcleritis, uveitis, oral aphthous ulcers, iritis erythema nodosum, pyoderma gangrenosum, Sweet's syndrome at Week 16. Resolution of arthropathy was defined as zero axial and peripheral arthropathies at Week 16.

Keywords: Crohn’s disease, ulcerative colitis, endoscopy, extra-intestinal manifestations

  1. Sandborn J, et al. ECCO 2019, OP14.
  2. Peyrin-Biroulet L, et al. ECCO 2019, DOP50.

Top image: © Pornpak Khunatorn

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