OP08 The effects of maintenance therapy with upadacitinib on abdominal pain, bowel urgency, and fatigue in patients with moderately to severely active Ulcerative Colitis: Phase 3 U-ACHIEVE maintenance results
Danese, S.(1);Tran, J.(2);D'Haens, G.(3);Rubin, D.T.(4);Aoyama, N.(5);Zhou, W.(2);James, B.(2);Yao, X.(2);SanchezGonzalez, Y.(2);Panaccione, R.(6);
(1)Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, n/a, Milano, Italy;(2)AbbVie Inc., n/a, North Chicago, United States;(3)Amsterdam University Medical Center, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(4)University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, United States;(5)Aoyama Medical Clinic, Department of Gastroenterology- Gastrointestinal Endoscopy and IBD Center, Kobe, Japan;(6)University of Calgary, Department of Gastroenterology and Hepatology, Calgary, Canada;
Abdominal pain (AP), bowel urgency (BU), and fatigue are debilitating symptoms that reduce quality of life in patients with active ulcerative colitis (UC). Results from two Phase 3 induction trials (U‑ACHIEVE induction [NCT02819635] and U‑ACCOMPLISH [NCT03653026]) showed significant improvements in AP, BU, and fatigue following induction with upadacitinib (UPA) in patients with active UC who had previously failed conventional or biologic therapy. We evaluated the effects of 52-week UPA maintenance treatment on AP, BU, and fatigue in patients who achieved a clinical response after induction.
ResultsResults from two Phase 3 induction trials (U‑ACHIEVE induction [NCT02819635] and U‑ACCOMPLISH [NCT03653026]) showed significant improvements in AP, BU, and fatigue following induction with upadacitinib (UPA) in patients with active UC who had previously failed conventional or biologic therapy. We evaluated the effects of 52-week UPA maintenance treatment on AP, BU, and fatigue in patients who achieved a clinical response after induction.
Four hundred fifty-one patients who achieved a clinical response after 8 weeks of induction with UPA 45 mg once daily (QD) were enrolled in the U-ACHIEVE maintenance study and were re-randomised 1:1:1 to UPA 15 mg QD (n=148), UPA 30 mg QD (n=154), or placebo (PBO) QD (n=149). Endpoints in this analysis were the percentage of patients who reported no AP or no BU at Weeks 0, 4, 8, 20, 28, 36 and 52, respectively, and the change in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) from induction baseline to Weeks 0 and 52 in the maintenance study. Patients recorded AP and BU daily via an electronic, handheld device. Lastly, the percentage of patients reporting a clinically meaningful within person change (MWPC), defined as ≥5-point increase in FACIT-F score from induction baseline, and normalization of fatigue, defined as a FACIT-F score >40 points, were determined at Weeks 0 and 52.
Significantly more patients reported no AP at Week 8 for UPA 15 mg vs PBO (60.8% vs 48.3%, p<0.05, Figure 1) and at Week 12 for UPA 30 mg vs PBO (59.7% vs 43.6%, p<0.01); significant differences were maintained through Week 52 (15 mg: 45.9%; 30 mg: 55.3% vs PBO: 20.8%, p<0.001). For no BU reported, significant differences vs PBO were observed with UPA 30 mg at Week 4 (68.8% vs 54.4%, p<0.05, Figure 2) and with UPA 15 mg at Week 8 (64.9% vs 49.7%, p<0.01) and were maintained through Week 52 (15 mg: 56.1%; 30 mg: 63.6% vs PBO: 17.4%, p<0.001). A significantly greater percentage of patients achieved MWPC in FACIT-F with both UPA 15 mg (55.4%) and UPA 30 mg (58.8%) compared with PBO (35.1%; p<0.001) at Week 52. In addition, a greater percentage of UPA-treated patients achieved normalization of fatigue (52.0% and 55.7% for UPA 15 mg and UPA 30 mg, respectively) vs PBO (35.7%) at Week 52 (p<0.01).
In patients with moderately to severely active UC who responded to UPA 45 mg induction treatment, significant and clinically meaningful improvements in patient-reported AP, BU, and fatigue achieved during induction were sustained through 52 weeks of UPA 15 mg or 30 mg maintenance treatment.