OP20 The effects of upadacitinib on ulcerative colitis symptom resolution and fatigue normalization in patients with moderately to severely active ulcerative colitis: Phase 3 U-ACHIEVE and U-ACCOMPLISH results
D'Haens, G.(1)*;Tran, J.(2,3);Danese, S.(4);Rubin, D.T.(5);Aoyama, N.(6);Lügering, A.(7);Klaff, J.(3);Xuan, S.(3);Ilo, D.(3);Sanchez Gonzalez, Y.(3);Panes, J.(8);
(1)Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(2)University of Washington, The Comparative Health Outcomes- Policy- and Economics Institute, Seattle, United States;(3)AbbVie Inc., n/a, Chicago, United States;(4)University Vita-Salute San Raffaele, n/a, Milan, Italy;(5)University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, United States;(6)Aoyama Medical Clinic, Department of Gastroenterology- Gastrointestinal Endoscopy and IBD Center, Kobe, Japan;(7)MVZ Portal10, n/a, Münster, Germany;(8)Hospital Clinic Barcelona- IDIPABS- CIBERehd, n/a, Barcelona, Spain;
Background
Abdominal pain (AP), bowel urgency (BU), stool frequency (SF), rectal bleeding (RB) and fatigue are debilitating symptoms that reduce quality of life in patients with ulcerative colitis (UC). Results from two Phase 3 induction trials and one maintenance trial (U‑ACHIEVE [NCT02819635] and U‑ACCOMPLISH [NCT03653026]) showed significant and clinically meaningful improvements in these symptoms following induction and maintenance treatment with upadacitinib (UPA) in patients with moderately to severely active UC. We evaluated the effects of 8-week UPA induction and 52-week UPA maintenance treatment on UC symptom resolution, defined as no BU, no AP, and symptomatic remission (no RB, SF≤1), and normalization of fatigue, defined as achievement of a Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) score ≥ 40.1.
Methods
A total of 988 patients were randomized in the U-ACHIEVE and U-ACCOMPLISH induction studies to receive UPA 45 mg once daily (QD; n=660) or placebo (PBO) QD (n=328). Patients who achieved a clinical response after 8 weeks of induction (n=451) were enrolled in the U-ACHIEVE maintenance study and re-randomised 1:1:1 to UPA 15 mg QD (n=148), UPA 30 mg QD (n=154), or PBO QD (n=149). Symptom resolution was assessed at induction Weeks 0, 2, 4, 6, 8 and maintenance Weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52. A more stringent assessment of symptom resolution and normalization of fatigue was conducted at Weeks 0, 2, and 8 of induction and Weeks 0 and 52 of maintenance.
Results
A higher percentage of patients achieved symptom resolution during induction treatment as early as Week 2 with UPA 45 mg vs PBO (11.1% vs 0.9%, p <0.001; Figure 1), and sustained through Week 8 (31.2% vs 7.9%, p<0.001). This difference was also observed during maintenance treatment among clinical responders starting at Week 8 with UPA (15 mg: 43.2%; 30 mg: 42.2% vs PBO: 30.2%, p<0.01 and p<0.05, respectively; Figure 2) and sustained through Week 52 (15 mg: 37.2%; 30 mg: 46.1% vs PBO: 12.8%, p<0.001 for both). Furthermore, the percentage of patients who achieved symptom resolution and fatigue normalization was greater with UPA vs PBO at Week 8 of induction (45 mg: 23.4% vs PBO: 6.7%, p <0.001; Figure 3) and Week 52 of maintenance (15 mg: 24.3%; 30 mg: 36.4% vs PBO: 12.1%, p<0.01 and p<0.001, respectively).
Conclusion
Patients with moderately to severely active UC were more likely to achieve symptom resolution and normalization of fatigue during induction treatment with UPA compared to PBO, and these benefits were sustained during maintenance therapy.
