P1107Comparison of effectiveness between ustekinumab and upadacitinib in patients with ulcerative colitis previously exposed to at least one anti-TNF agent: results from the real-world evidence multicenter UPPERCUT study

Background We compared the effectiveness of ustekinumab (UST) and upadacitinib (UPA) in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent. Methods This was a multicenter retrospective study that consecutively included all patients aged ≥18 years-old with symptomatic UC (partial Mayo score >2) who initiated UST or UPA after exposure to at least one anti-TNF. UST was initiated with an intravenous infusion followed by SC injections of 90 mg every 8 weeks, with the option of intensification to 90 mg every 4 weeks from week 4 at the clinician’s discretion. UPA was prescribed at 45 mg once daily for 8 weeks, followed by 45 mg, 30 mg, or 15 mg at the physician’s discretion. The primary endpoint was symptomatic remission (partial Mayo score ≤2) without corticosteroids (CFREM) at week 16 (W16). Secondary endpoints were clinical remission per modified Mayo score, and histological and endoscopic improvement (HEMI). Comparisons were made using propensity-score analyses adjusted on the usual potential confounders. Results A total of 226 patients were included (165 and 61 in UST and UPA groups, respectively). Except for higher proportion of prior exposure to more than two biologics (46.6% vs 82.0%; p < 0.001) in UPA group, the populations were comparable (UST vs UPA). After propensity score adjustment, CFREM at W16 was 35.1% and 37.2% in UST and UPA groups, respectively (p = 0.91). Subgroup analyses (after propensity adjustment) did not show any difference in CFREM at W16 after failure to only one biologic, whereas UPA was significantly more effective than UST (OR = 6.05 [1.10–33.42]; p = 0.039), after exposure to ≥ 2 advanced therapies, as well as in patients with primary failure to ≥ 2 prior biologics (OR = 4.25 [1.11–16.28]; p = 0.035). However, no difference was observed between the two treatments according to UC severity. No predictor of UPA effectiveness was identified. Factors associated with absence of CFREM at W16 under UST were: failure of ≥ 3 biologics (p = 0.013) and primary failure to at least one biologic (p = 0.013). No difference was observed between the two treatments regarding clinical remission and HEMI (p = 0.48 and 0.68, respectively). After a median follow-up > 12 months, we did not see any difference regarding treatment discontinuation, UC-related hospitalization, or colectomy. Conclusion In this study, UST and UPA appeared to have comparable effectiveness in the overall population of UC patients previously exposed to at least one anti-TNF. However, UPA was more effective than UST in patients exposed to at least two biologics and/or with at least two prior primary failures. These results may help physicians to personalize therapeutic decision-making in UC. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Serrero, Melanie: fees from Pfizer, Abbvie, Takeda, Janssen, MSD, Amgen, Ferring, Tillotts, Celltrion Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Vuitton, Lucine: No conflict of interest Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Domas, Quentin: No conflict of interest Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson&Jonhson, MSD, Pfizer, Takeda, Sandoz Hupé, Marianne: No conflict of interest Pereira, Bruno: No conflict of interest Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer