P601 Upadacitinib improves steroid-free clinical and endoscopic endpoints in patients with Crohn’s disease: Data from the CELEST study

• Published in: Journal of Crohn's and colitis Vol. 12; no. supplement_1; pp. S412 - S413
• Main Authors: Panaccione, R, Atreya, R, Ferrante, M, Dubinsky, M C, Sands, B E, Abreu, M T, Cataldi, F, Enejosa, J V, Zhou, Q, Huang, B, Lacerda, A P, Pangan, A L
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 16-01-2018
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.728

Abstract
Background
The efficacy and safety of upadacitinib (UPA), an oral selective JAK1 inhibitor, were assessed in patients with moderate-to-severe Crohn’s disease (CD) and with inadequate response/intolerance to an immunomodulator or tumour necrosis factor inhibitor (TNFi).1 We report the steroid-free endpoints in the 16-week induction phase of CELEST in patients receiving corticosteroid (CS) at baseline (BL).
Methods
Patients with CD Activity Index (CDAI) 220–450, average daily very soft/liquid stool frequency (SF) ≥2.5 or abdominal pain score (AP) ≥2.0 and Simplified Endoscopic Score for CD (SES-CD) ≥6 (or ≥4 for those with isolated ileal disease) were randomised equally to receive either placebo (PBO) or UPA 3, 6, 12, 24 mg twice daily (BID) or 24 mg once daily (QD) for 16 weeks. Patients were also randomised 1: 1 at BL for follow-up ileocolonoscopy at either 12 or 16 weeks. Beginning at Week 2, CS was tapered in patients on CS at BL. The proportion of patients who discontinued CS and achieved endoscopic remission, endoscopic response, clinical remission, modified clinical remission (all defined in Figure), and CDAI <150 were assessed at Week 16 in patients on CS at BL. Patients with missing data or who prematurely discontinued or received CS dose higher than BL were considered non-responders. Comparisons of each dose of UPA vs. PBO were performed using Chi-square test. Treatment-emergent adverse events (AEs) collected throughout the study in patients with at least one UPA dose up to 30 days of the last dose were stratified by CS use at BL.
Results
Among 220 randomised patients, 96 (43.6%) received CS at BL: median (min–max) age 38.5 (19.0–69.0) years, CDAI 291.0 (162–599), CD duration 9.4 (0.1–44.7) years and 95 (99.0%) had failed one or more TNFi. More patients taking UPA were able to discontinue CS and achieve endoscopic endpoints at 12 of 16 weeks and clinical endpoints at 16 weeks than patients on PBO (Figure). Patients on 24 mg BID achieved a statistically significant difference from PBO in all clinical remission endpoints. The rates of any AEs were similar between patients with or without CS use in the UPA (85.2% and 80.4%, in all UPA arms, respectively) and PBO groups (73.3% and 72.7%).
Figure.
Proportion of subjects who discontinued corticosteroid and achieved clinical and endoscopic endpoints at 16 weeks.
Conclusions
Patients with long-standing CD refractory to conventional/TNFi therapy who received CS at BL achieved statistically significant steroid-free endoscopic and clinical improvements at 16 weeks of treatment with UPA. The safety profile of UPA in patients taking CS at BL was consistent with the overall study population.
Reference
1. Sandborn WJ et al. Gastroenterology 2017;152(Suppl. 1):S1308–9.