P630 Upadacitinib Improves Clinical Outcomes in Patients with Moderate to Severely Active Crohn’s Disease Irrespective of Previous Failure to Respond to Biologics or Conventional Therapies
Schreiber, S.W.(1)*;Lim, A.(2);Lacerda, A.P.(3);Allegretti, J.R.(4);Watanabe, K.(5);Lukin, D.(6);Dubenco, E.(3);Ford, S.(3);Oomen, J.(3);Zhou, Q.(3);Liu, J.(3);Louis, E.(7);
(1)University Hospital Schleswig-Holstein- Christian Alrechts University, Department Internal Medicine, Kiel, Germany;(2)University of Alberta, Division of Gastroenterology- Department of Medicine, Edmonton, Canada;(3)AbbVie, none, North Chicago, United States;(4)Brigham and Women's Hospital, Division of Gastroenterology- Department of Internal Medicine, Boston, United States;(5)Hyogo Medical University, Division of Gastroenterology and Hepatology- Department of Internal Medicine-, Hyogo, Japan;(6)New York Presbyterian/Weill Cornell Medical Center, Department of Gastroenterology and Hepatology, New York, United States;(7)University Hospital CHU of Liège, Hepato-Gastroenterology and Digestive Oncology Department, Liège, Belgium;
Background
Upadacitinib (UPA), an oral, selective Janus kinase inhibitor, demonstrated significantly greater efficacy compared with placebo (PBO) in patients (pts) with moderately to severely active Crohn’s disease (CD) in phase 3 multicentre, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED, and maintenance U-ENDURE trials.1-3 This analysis compared clinical outcomes in pts treated with UPA vs PBO once daily (QD) among pts without or with a history of biologic failure.
Methods
Eligible pts with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for pts with isolated ileal disease) were randomized (2:1) to UPA 45 mg (UPA45) or PBO in U-EXCEL and U-EXCEED. Induction responders (≥30% decrease in average daily very soft/liquid SF and/or APS, neither worse than baseline) to 12-week (wk) UPA45 were re-randomized 1:1:1 for maintenance to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO QD in U-ENDURE. Clinical remission, response (CR-100), and maintenance of clinical remission, along with adverse events (AEs) were assessed through maintenance wk 52.
Results
Baseline demographics/characteristics were similar for all treatment groups; pts with prior biologic failure were 71.5% PBO and 72.0% UPA45 in induction and 76.4% PBO, 73.4% UPA15 and 75.6% UPA30 in maintenance. Among pts without/with biologic failure history, those treated with UPA45 exhibited higher rates for clinical remission at wk 12 (CDAI: UPA45 54.1%/40.5% vs PBO 39.4%/19.4%; SF/APS: UPA45 54.0%/42.2% vs PBO 28.3%/14.1%, Fig. 1A). Similar results were observed at wk 52 with UPA15 and UPA30 vs PBO (Fig. 1B). Irrespective of biologic failure status, a higher proportion of patients on either UPA dose maintained clinical remission from maintenance wk 0 to wk 52 (Fig. 1C). Higher proportions of pts with prior biologic failure achieved CR-100 with UPA45 vs PBO at wk 12 (53.2% vs 26. 9%); at wk 52 differences from PBO were found for either UPA dose in pts without or with prior biologic failure (Fig. 1D). Serious AEs and serious infections were similar across treatment groups (Tables 1-2). No tuberculosis or adjudicated cardiovascular events were reported. Malignancy, opportunistic infections, thrombotic events, and gastrointestinal perforations were infrequent (<1.0% or 10 E/100PY).
Conclusion
All upadacitinib doses achieved greater clinical efficacy than placebo during induction and maintenance periods, irrespective of patient prior exposure to biologic therapy, with an acceptable safety profile.