P0749Association of endoscopic outcomes with long-term clinical improvements in patients with moderately to severely active Crohn’s disease treated with upadacitinib: Results from the U-ENDURE long-term extension study

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD), in line with European Crohn’s and Colitis Organisation CD guidelines, as it is associated with improved long-term disease outcomes. We assessed the relationship between endoscopic healing and long-term clinical outcomes, patient-reported outcomes (PROs) and hospitalisations in patients (pts) with moderately to severely active CD receiving upadacitinib (UPA) maintenance treatment in the U-ENDURE long-term extension (LTE) study. Methods Pts completing the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Pts receiving UPA 15 mg or 30 mg once daily in LTE were included in this analysis. Clinical remission based on CD activity index (CDAI 150), CDAI response (≥100-point decrease in CDAI from induction baseline), clinical remission based on stool frequency/abdominal pain (SF/AP) score (average daily soft or liquid SF ≤ 2.8 and average daily AP ≤ 1.0, and neither greater than induction baseline), Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total IBDQ score from induction baseline) and remission (IBDQ total score ≥170 points), Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) response (≥9-point increase from induction baseline), and economic outcomes (CD-related hospitalisations or surgeries) were evaluated at LTE week 96. Outcomes were compared between pts who achieved vs those who did not achieve endoscopic response, endoscopic remission, or ulcer-free endoscopy (endoscopic outcomes defined in Table footnote) at maintenance week 52 using chi-square testing (nominal P values). Pts with missing outcomes at LTE week 96 were imputed as nonresponders. Results Of 244 pts, 153/244 (62.7%), 112/244 (45.9%) and 89/242 (36.8%) achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at LTE week 0. Significantly (all nominal P≤0.05) more pts who achieved endoscopic response, endoscopic remission or had an ulcer-free endoscopy at LTE Week 0 achieved CDAI response, CDAI remission, SF/AP clinical remission, IBDQ response, IBDQ remission and FACIT-F response at LTE week 96 (Table). CD-related hospitalisations or surgeries at LTE week 96, were significantly (nominal P≤0.05) lower in pts with endoscopic remission and ulcer-free endoscopy at LTE week 0, and numerically lower in pts with endoscopic response. Conclusion A significantly higher proportion of pts who achieved endoscopic outcomes at 52 weeks and received up to 3 years of UPA maintenance treatment achieved long-term improvements in clinical and PROs and reduced CD-related hospitalisations or surgeries. Conflict of interest: Loftus, Jr, Edward: Edward V. Loftus, Jr. has received consulting fees from AbbVie, Abivax, Astellas, Avalo Therapeutics, Biocon, BMS, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic Therapeutics, Ono Pharma, Spyre Therapeutics, Takeda, and TR1X Bio has received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda and holds stock in Exact Sciences and Moderna. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen