Efficacy and Safety of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From a Randomized Phase 3 U-EXCEL Study

ABSTRACT

Introduction: Eligible patients(N=526) with moderate to severe active Crohn’s Disease(CD), defined as average daily stool frequency(SF)≥4 and/or abdominal pain score(APS)≥2, and a Simple Endoscopic Score for CD(SES-CD) (excluding the narrowing component subscore) ≥6(≥4 for subjects with isolated ileal disease). PBO % [95% CI] h Co-Primary Endpoints Clinical remission, wk 12  Per CDAI a  Per SF/APS b 29.1 [22.4, 35.8] 22.2 [16.0, 28.3] 49.5 [44.2, 54.8] 50.7 [45.5, 56.0] 20.8 [12.7, 28.8]** 28.7 [20.9, 36.4]** Endoscopic response c , wk 12 13.1 [8.1, 18.0] 45.5 [40.3, 50.8] 33.0 [26.2, 39.9]** Key Secondary Endpoints Clinical Remission, wk 4  Per CDAI a  Per SF/APS b 26.7 [20.2, 33.3] 14.8 [9.5, 20.0] 37.1 [32.1, 42.2] 35.7 [30.7, 40.7] 10.8 [2.9, 18.6]* 21.2 [14.3, 28.2]** Corticosteroid-free clinical remission, wk 12  per CDAI d  per SF/APS d (N=64) 15.7 [6.8, 24.7] 12.5 [4.4, 20.6] (N=126) 42.9 [34.2, 51.5] 44.4 [35.8, 53.1] 27.7 [15.7, 39.8]** 32.6 [21.5, 43.7]** Clinical Response CR-100 e  Week 2  Week 12 20.4 [14.4, 26.5] 37.3 [30.1, 44.5] 32.2 [27.3, 37.1] 56.6 [51.4, 61.8] 11.7 [4.2, 19.2]* 19.8 [11.3, 28.4]** Endoscopic remission f , wk 12 7.4 [3.5, 11.3] 28.9 [24.2, 33.7] 21.8 [15.8, 27.8]** Patient randomization was stratified by baseline corticosteroid use, endoscopic disease severity, and the number of previously failed biologics. All patients within this dataset were included here within the ITT population. a Clinical remission per CDAI = per US, CDAI < 150. b Clinical remission per SF/APS = per EU, average daily SF ≤ 2.8 and average daily APS ≤ 1.0 and both not greater than baseline c Endoscopic response = decrease in SES-CD > 50% from baseline (or for subjects with a baseline SES-CD of 4, at least a 2-point reduction from baseline), as scored by a central reviewer. d Corticosteroid-free clinical remission = discontinuation of corticosteroid use and achievement of clinical remission per CDAI or SF/APS at wk 12 among patients on corticosteroids at baseline. e Clinical response-100 = decrease of ≥ 100 points in CDAI from baseline. f Endoscopic remission = SES-CD ≤ 4, at least a 2-point reduction versus baseline and no subscore >1 in any individual variable, as scored by a central reviewer. g Results are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C). h 95% CI for adjusted difference and p-value are calculated according to the Cochran-Mantel-Haenszel (CMH) test adjusted for randomization strata. **P ≤ .0001 or *P ≤ .01 vs PBO;Average daily abdominal pain score, APS;Coronavirus disease 2019, COVID-19;Confidence Interval, CI;Crohn’s Disease Activity Index, CDAI;Simple Endoscopic Score for CD, SES-CD, Placebo, PBO;Once daily, QD;average daily very soft/liquid stool frequency, SF;Upadacitinib, UPA.