DOP38 Upadacitinib Therapy Reduces Crohn’s Disease Symptoms Within the First Week of Induction Therapy

Abstract Background Upadacitinib (UPA), an oral, selective JAK inhibitor demonstrated superior efficacy for clinical remission compared with placebo (PBO) and acceptable safety profile in patients moderately to severely active Crohn’s disease (CD) 2 phase 3 induction trials, U-EXCEL (NCT03345849) U-EXCEED (NCT03345836).1-2 There remains unmet need therapies that provide rapid symptom relief ambulatory moderate severe CD experiencing flares. This sub-analysis evaluated the of UPA 45 mg once daily (UPA45) on early symptomatic improvement first 15 days treatment, using pooled data from U-EXCEED. Methods were multicentre, double-blind, PBO-controlled trials enrolled who had average very soft or liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2 at baseline, plus a Simple Endoscopic Score ≥6 (≥ 4 isolated ileal disease), excluding narrowing component. Patients (n=1021) randomized (2:1 ratio) receive UPA45 (n=674) PBO (n=347) 12 weeks. First dose study drug was administered day 1. Improvement symptoms SF APS, addition time achievement SF/APS assessed. Results treated experienced significant PBO-treated patients, simultaneously achieving < APS ≤ 1 beginning (9.6% vs. 5.8% PBO) (P≤0.05, Figure 1A). Difference maintained through (P≤0.05), except (P=0.0518). Similar results found when evaluating each separately, higher proportion received either 3, 5 (31.6% 23.1% PBO, 1B). UPA-treat attained significance 6 (49.1% 39.3% 1C), PBO. Differences sustained (P≤0.01 both endpoints). A greater receiving also least 60% decrease by 5, which (P≤0.01, 1D). achieved significantly earlier than (median remission: 13 vs 32 PBO; P<0.0001, 2). Conclusion improved diarrhea within week treatment faster providing relief.