P1156Association Between Histologic and Endoscopic Outcomes With Long-Term Clinical and Symptomatic Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis Treated With Upadacitinib

Abstract Background Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for adults with moderately to severely active UC, 1 has shown early achievement (at week 8 of induction) of composite histologic-endoscopic endpoints, which is associated with favourable clinical and symptomatic outcomes. 2 This post hoc analysis evaluated the association between achieving either histologic or endoscopic outcomes and composite histologic-endoscopic, clinical, and symptomatic outcomes. Methods Patients with UC who achieved a clinical response at week 8 of induction therapy with UPA 45 mg once daily (QD) in the U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026) studies enrolled into the phase 3 U-ACHIEVE (NCT02819635) maintenance study and were randomized 1: 1: 1 to receive UPA 15 mg QD (UPA15), UPA 30 mg QD (UPA30), or placebo for 52 weeks. Histologic improvement (HI), histologic remission (HR), endoscopic improvement (EI), endoscopic remission (ER), histologic endoscopic mucosal improvement (HEMI) and histologic endoscopic mucosal remission (HEMR) were assessed at weeks 0 (week 8 of induction) and week 52 of maintenance. 3 Clinical remission and corticosteroid (CS) -free remission, no bowel urgency, and no abdominal pain were assessed at week 52 of maintenance. All outcomes are defined in the Figure legends. Safety was not assessed in this post hoc analysis but has been published previously. 4 Results Early achievement (when entering the maintenance study) of histologic or endoscopic outcomes with UPA was associated with achievement of HEMI and HEMR after 52 weeks of maintenance UPA, except for association of HI at week 0 with HEMI at week 52 with UPA30 (Figure 1). Patients who achieved HEMI with UPA15 when entering the maintenance study had significantly greater rates of clinical remission, CS-free remission, or no bowel urgency at week 52 compared with those who did not achieve HI or EI (Figure 2). Patients who achieved HEMI or EI at week 52 of maintenance UPA30 had significantly greater rates of clinical remission (HEMI: 85. 6%; EI: 86. 7%), CS-free remission (84%; 86. 7%), no bowel urgency (85. 6%; 80%), or no abdominal pain (77. 6%; 60%) at week 52 vs those who did not achieve HI or EI. UPA15 followed similar trends. Conclusion Early achievement of individual histologic or endoscopic outcomes with UPA was associated with achievement of composite histologic-endoscopic outcomes at 52 weeks of maintenance. Patients who achieved HEMI with UPA when entering the maintenance study had favourable clinical and symptomatic outcomes. This analysis supports the use of composite histologic-endoscopic endpoints over individual histologic or endoscopic endpoints as a treatment goal for patients with UC. References: 1. Turner D, et al. , Gastroenterology. 2021;160: 1570–1583. 2. RINVOQ (Upadacitinib) Prescribing Information. Accessed June 20, 2025. https: //www. rxabbvie. com/pdf/rinvoqₚi. pdf. 3. Parkes G, et al. , J Gastroenterol. 2023;58: 990–1002. 4. Vermeire, et al. , Lancet Gastroenterol Hepatol. 2023;8: 976–989. Conflict of interest: Prof. Dr. Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp &amp Dohme, Sandoz, Takeda, UCB, Vifor. Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Morisset, Pierre: is an employee of AbbVie Inc. and may own stock and/or options. Cheng, Erica: is an employee of AbbVie Inc. and may own stock and/or options. Perkovic, Ashley: is an employee of AbbVie Inc. and may own stock and/or options. Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc. , Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc. , Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc. , Gilead, Janssen, Mylan, Pfizer, Takeda.