Abstract Background With an expanding therapeutic armamentarium for ulcerative colitis (UC), the optimal first-line biologic therapy in biologic-naïve patients remains uncertain1,2. Although biologics have transformed UC management, direct real-world comparisons are lacking. The aim of this study was to compare the real-world effectiveness and safety of currently available biologic therapies in biologic-naïve patients with UC, to inform optimal first-line treatment selection in clinical practice. Methods In this multicentre, retrospective cohort study, biologic-naïve adults with UC initiating infliximab, adalimumab, vedolizumab, ustekinumab, or mirikizumab as first-line biologic therapy were included. The primary endpoint was steroid-free clinical remission (SFCR) at 6 and 12 months; secondary endpoints included biochemical SFCR, endoscopic improvement and remission, deep remission, treatment persistence, and safety. Inverse probability of treatment weighting (IPTW) based on multinomial propensity scores was applied to balance baseline confounders across treatment groups. Weighted logistic and Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Kaplan–Meier analyses were used to assess the probability of achieving SFCR and treatment persistence over time. Results A total of 360 biologic-naïve patients with ulcerative colitis were included: infliximab (n = 84), adalimumab (n = 54), ustekinumab (n = 72), mirikizumab (n = 60), and vedolizumab (n = 90). After IPTW, the 6-month cumulative probabilities of achieving SFCR (fig. 1) were 74.2% for mirikizumab, 65.8% for ustekinumab, 58.5% for infliximab, 47.5% for vedolizumab, and 36.3% for adalimumab. Mirikizumab showed a significantly higher probability of remission compared with infliximab (HR 2.22; 1.12–4.40; p = 0.023), adalimumab (HR 4.03; 1.87–8.65; p 0.001), and also outperformed vedolizumab (HR 0.34; 0.18–0.67; p = 0.002). Ustekinumab achieved higher remission rates than adalimumab (HR 2.28; 1.06–4.89; p = 0.034), while differences versus infliximab and vedolizumab were not significant. A similar pattern was observed for biochemical remission, with 6-month probabilities of 52.6% for mirikizumab, 49.1% for ustekinumab, 40.8% for infliximab, 37.1% for vedolizumab, and 23.2% for adalimumab. Conclusion Mirikizumab and ustekinumab showed a trend toward greater real-world effectiveness compared with anti-TNF agents and vedolizumab as first-line biologics in biologic-naïve ulcerative colitis. These preliminary findings suggest that selective anti-IL-12/23 and anti-IL-23 therapies may represent effective and well-tolerated first-line options in clinical practice. References: 1. Kapizioni C, Desoki R, Lam D, et al. Biologic Therapy for Inflammatory Bowel Disease: Real-World Comparative Effectiveness and Impact of Drug Sequencing in 13 222 Patients within the UK IBD BioResource. J Crohns Colitis. 2024;18(6):790-800. doi:10.1093/ECCO-JCC/JJAD203. 2. Laredo V, Gargallo-Puyuelo CJ, Gomollón F. How to Choose the Biologic Therapy in a Bio-Naïve Patient with Inflammatory Bowel Disease. J Clin Med. 2022;11(3):829. doi:10.3390/JCM11030829/S1. Conflict of interest: Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Furfaro, Federica: Grant: IG-IBD Personal Fees: Pfizer, Biogen, J&J, Abbvie, Amgen, Janssen Privitera, Giuseppe: Consultant fee from Johnson & Johnson Dr. Ferretti, Silvia: No conflict of interest Migliorisi, Giulia: No conflict of interest Scardino, Giulia: No conflict of interest Quadarella, Alessandro: No conflict of interest Orlando, Stefania: Consultancy fees from Abbvie Saibeni, Simone: Consultancy, lecture fees, and advisory board for AbbVie, Alfasigma, Arena, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Johnson & Johnson, MSD, Pfizer, and Takeda. Bergna, Irene Maria Bambina: No conflict of interest Cannatelli, Rosanna: No conflict of interest Viganò, Chiara: Consultancy and lecture fees from: AbbVie, Galapagos, Janssen-Cilag, Johnson & Johnson, Pfizer, Takeda, Celltrion, Alfasigma, Eli Lilly and research grant from Celltrion and Pfizer. Bruno, Alessandro: No conflict of interest 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 Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda
Bezzio et al. (Thu,) studied this question.