P179 Comparative benefit-risk profile of induction and maintenance therapy with upadacitinib versus placebo in patients with moderately to severely active ulcerative colitis
Blumenstein, I.(1)*;Xuan, S.(2);Panaccione, R.(3);Baert, F.(4);Barreiro-de Acosta, M.(5);Ye, B.D.(6);Klaff, J.(2);Vladea, R.(2);Levy, G.(2);Holweg, C.T.J.(2);Sanchez Gonzalez, Y.(2);Dubinsky, M.C.(7);
(1)Goethe University Clinic, n/a, Frankfurt, Germany;(2)AbbVie Inc, n/a, North Chicago, United States;(3)University of Calgary, Department of Gastroenterology and Hepatology, Alberta, Canada;(4)AZ Delta, Department of Gastroenterology, Roeselare, Belgium;(5)University Hospital of Santiago de Compostela, Inflammatory Bowel Disease Unit, Galicia, Spain;(6)Asan Medical Centre- University of Ulsan College of Medicine, Department of Gastroenterology and Inflammatory Bowel Disease Center, Seoul, Korea- Republic Of;(7)Icahn School of Medicine at Mt. Sinai, Susan and Leonard Feinstein IBD Center, New York, United States;
Background
Upadacitinib (UPA) demonstrated efficacy and safety as induction and maintenance therapy for ulcerative colitis (UC) in Phase 3 trials U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). This post-hoc analysis aims to characterise the benefit-risk profile of UPA induction and maintenance therapy vs placebo (PBO) in patients (pts) with moderately to severely active UC based on a number needed to treat/harm (NNT/NNH) analysis.
Methods
Efficacy and safety data from the pooled intention-to-treat population of U-ACHIEVE and U-ACCOMPLISH trials were included. Pts received UPA 45 mg (UPA45) once daily (QD) or PBO for 8 weeks (induction trials). Clinical responders (per Adapted Mayo score) at Week 8 of induction were re-randomised to receive UPA 15 mg (UPA15) or 30 mg (UPA30) QD, or PBO in the 52-week maintenance study. The primary efficacy endpoint was clinical remission per Adapted Mayo score. Secondary outcomes are listed in Table 1 and safety outcomes are listed in Table 2. N, percentages, and outcome differences compared by Z test were reported. NNT/NNH was calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes for UPA vs PBO. Positive NNT values indicate greater efficacy and negative NNH values imply lower safety risk for UPA vs PBO.
Results
A significantly greater proportion of pts achieved clinical remission at induction (UPA45 29.9% vs PBO 4.4%) and maintenance (UPA15 40.4%, UPA30 53.6% vs PBO 10.8%) with UPA vs PBO, as well as all secondary endpoints (all p<0.001; Table 1). The NNT for clinical remission at Week 8 was 4.0, ranging from 2.1 to 9.6 for secondary endpoints. At Week 52, the NNT for clinical remission was 2.4; NNTs for secondary endpoints ranged from 1.8 to 5.9 (Table 1). At Week 8, adverse events (AEs) were lower for worsening of UC for UPA45 vs PBO-treated pts and greater for creatine phosphokinase (CPK) elevation, acne, neutropenia, and lymphopenia (p≤0.01). At Week 52, AEs were lower for UPA15 and UPA30 vs PBO for worsening of UC, AEs leading to discontinuation (UPA15 only), and arthralgia (UPA30 only), and greater for CPK elevation, herpes zoster, hepatic disorder (UPA15 only), and neutropenia (UPA30 only) (p≤0.05; Table 2). All other AEs were similar between UPA and PBO. Among the safety outcomes significantly different between UPA and PBO, the NNH for UPA vs PBO ranged from –16.1 to 25.6 (Table 2).
Conclusion
This post-hoc Phase 3 analysis demonstrates greater efficacy and generally comparable safety of UPA vs PBO, indicating a favourable benefit-risk profile for UPA in pts with moderately to severely active UC.
