Zhou,11 Aileen Pangan,11 Xavier Hebuterne,3 Hiroshi Nakase,4 Geert D’Haens,5 Julian Panes,6 James O. Lindsay,7 Peter D. R. Higgins,8 Edward Loftus, Jr.,9 William Sandborn,10 Wangang Xie,11 Yuri Sanchez Gonzalez,11 Jianzhong Liu,11 Michael A. Weinreich,11 Severine Vermeire12 Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients with Moderately to Severely Active Ulcerative Colitis: Results from a Randomized Phase 3 Study 1Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada; 2Humanitas University and Humanitas Research Hospital, IRCCS, Milan, Italy; 3Department of Gastroenterology and Clinical Nutrition, CHU de Nice, Université Côte d’Azur, Nice, France;4Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan; 5Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, Netherlands; 6Hospital Clinic Barcelona, IDIPABS, CIBERehd, Barcelona, Spain; 7Department of Gastroenterology, The Royal London Hospital, Barts Health NHS Trust, London, UK; 8University of Michigan, Ann Arbor, Michigan, USA; 9Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 10Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA; 11AbbVie, Inc, North Chicago, IL, USA; 12Department of Gastroenterology & Hepatology, University Hospital Leuven, Leuven, Belgium # 64
bowel disease, where patients experience recurring symptoms of diarrhea, abdominal pain, and bowel urgency. • The Janus Kinase (JAK) family is composed of intracellular signalling proteins that regulate inflammatory signal transduction pathways and are involved in the pathogenesis of UC.3 - Upadacitinib (UPA) is an oral selective and reversible JAK inhibitor currently under investigation for the management of UC. • UPA demonstrated significantly greater efficacy as an induction therapy compared with placebo (PBO) in patients with moderately to severely active UC during two phase 3 induction trials (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]).4,5 The Need for a Targeted Ulcerative Colitis Maintenance Therapy 1.Kaur A, Goggolidou P. J Inflamm. 2020 Apr 21;17:15. 2.Monstad IL, et al. J Crohns Colitis. 2020 Dec 2:jjaa232. 3.Salas et al. Nature Reviews: Gastroenterology and Hepatology. 2020; 17: 323-337. 4.Danese S. et al. Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study. European Crohn’s and Colitis 2021 Congress. 5. Vermeire S. et al. Efficacy and safety of upadacitinib as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from phase 3 U- ACCOMPLISH study. European Crohn’s and Colitis 2021 Congress. OBJECTIVE: To evaluate the efficacy and safety of UPA 15 mg (UPA15) once daily (QD) and UPA30 (UPA30) mg QD compared to PBO as maintenance therapy for patients with moderately to severe UC who responded to UPA induction treatment.
Design Induction Studies (NCT02819635) (N = 278) Induction Study (NCT03653026) (N = 152) Primary endpoint: clinical remission Secondary Endpoints • Randomization into the maintenance study was stratified by previous biologic failure status, clinical remission during induction and corticosteroid use at week 0. U-ACHIEVE maintenance study (N=451; 52 wk) UPA 15 mg QD N=148 UPA 30 mg QD N=154 PBO QD N=149 Double blind; Randomization 1:1:1 8 wk - UPA 45 mg QD Clinical responders§ N = 451 § Clinical responders were defined as patients that successfully achieved clinical remission per Adapted Mayo score at the end of the 8-week induction period. QD, once daily; UPA, upadacitinib; CS, corticosteroid; wk, week Phase 2b M14-234 (N = 21)
Clinical Endpoint Definition Primary endpoint: clinical remission (Per Adapted Mayo Score) SFS ≤1 and not greater than baseline, RBS=0, and Mayo endoscopic subscore ≤1 Secondary endpoints Maintenance of clinical remission Clinical remission among patients that achieved clinical remission at the end of the induction therapy Corticosteroid-free clinical remission Clinical remission and corticosteroid-free for ≥90 days prior to wk 52 among patients with clinical remission at the end of the induction therapy Maintenance of clinical response Decrease from baseline of induction in Adapted Mayo score ≥ 2 points and ≥ 30%, PLUS a decrease in RBS ≥ 1 or an absolute RBS ≤ 1 among patients who achieved clinical response at the end of induction therapy Endoscopic improvement Endoscopic subscore ≤ 1 Maintenance of endoscopic improvement Endoscopic improvement among patients with endoscopic improvement at the end of the induction therapy Endoscopic remission Endoscopic subscore = 0 HEMI (Histologic-endoscopic mucosal improvement) Endoscopic subscore ≤ 1 and Geboes score ≤ 3.1
based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19. Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of all primary and key secondary endpoints at the 0.05 level. Error bars are ±95% CI. *** P-value < 0.001. CS, Corticosteroid UPA15 and UPA30 Achieve Significance Compared to PBO for Maintenance of Clinical Remission, CS-free Clinical Remission and Maintenance of Clinical Response Secondary Endpoints (all at week 52) 0 20 40 60 80 100 Percentage of Patients Maintenance of clinical remission CS-free clinical remission Maintenance of clinical response Number of patients: 54 47 58 54 47 58 134 135 144 22% 59% 70% 22% 57% 68% 19% 63% 77% *** *** *** *** *** *** 0 20 40 60 80 100 Percentage of Patients Maintenance of clinical remission CS-free clinical remission Maintenance of clinical response Number of patients: 54 47 58 54 47 58 134 135 144 22% 59% 70% 22% 57% 68% 19% 63% 77% *** *** *** *** *** *** PBO UPA15 UPA30 A B C
to severely active UC. No new types of important safety risks were observed compared to the known safety profile of UPA. Higher rates of certain AESI were reported in UPA treatment arms. UPA30 demonstrated numerically greater clinical efficacy of approximately 10% compared to UPA15 for most endpoints. UPA15 and UPA30 had Significantly Greater Efficacy Compared to PBO for All Primary and Secondary Endpoints at Week 52 Based on Clinical, Endoscopic, and Histologic Evaluations