S773 Rapidity of Symptom Control with Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From Two Randomized Phase 3 Studies

Abstract

Introduction: Upadacitinib (UPA) is an oral, selective JAK inhibitor investigated for treatment of several immune-mediated inflammatory diseases, including ulcerative colitis (UC). Safety and efficacy of UPA in patients (pts) with moderately to severely active UC were studied in the phase 3 induction trials, U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). We assessed early (week 2) symptomatic improvement and decrease in biomarkers of inflammation during induction therapy with UPA 45 mg once daily (QC) compared with placebo (PBO). Methods: In the multicentre, double-blind, PBO-controlled U-ACHIEVE and U-ACCOMPLISH trials, pts with moderately to severely active UC were randomized 2:1 to UPA 45 mg QD or PBO for 8 weeks. This analysis evaluated the proportions of pts with clinical remission (per partial Mayo score), clinical response (per partial Mayo score), stool frequency subscore (SFS) ≤1, and rectal bleeding subscore (RBS) of 0, as well as change from baseline in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) at week 2 with UPA vs PBO. Statistical comparison between the two groups was performed according to the Cochran-Mantel-Haenszel test adjusted for baseline corticosteroid use (yes or no), baseline Adapted Mayo score (≤7 or >7), according to prior biologic response (bio-IR, biologic inadequate response/bio failure; non-bio-IR, nonbiologic inadequate response/non-bio-failure). Results: As early as week 2, a significantly higher proportion of pts who received UPA achieved clinical remission per partial Mayo score (23%) compared with PBO (5%; treatment difference, [95% CI]: 17.4 [11.8, 23.1]; P < 0.001) in U-ACHIEVE. Results were similar in U-ACCOMPLISH at week 2: UPA (31%) versus PBO (3%); treatment difference (95% CI): 26.5 (20.9, 32.1; P < 0.001). Similarly, higher proportions of pts receiving UPA 45 mg QD achieved other efficacy endpoints, including clinical response, SFS ≤1 and RBS = 0, at week 2 vs PBO (Table 1). Significant decreases from baseline in markers of inflammation (fecal calprotectin and hsCRP levels) were also observed with UPA vs PBO in both trials (Table 1). Safety was comparable with the known safety profile of UPA, and no new safety signals were identified. Conclusion: UPA 45 mg QD achieved rapid improvement in both symptomatic and objective biomarker measures as early as week 2 compared with PBO in pts with moderately to severely active UC. The results demonstrate rapid onset of treatment effect with UPA.Table 1.: Baseline Clinical Characteristics of Patients with Perianal Crohn's Disease