DOP084Ustekinumab and vedolizumab in the treatment of fistulising Crohn’s disease: a propensity score-matched analysis from the prospective Persistence Australian National Inflammatory Bowel Disease Cohort (PANIC5) study

Background There are spare data for non-tumour necrosis factor inhibitors (non-TNFis) in fistulising Crohn’s disease (FCD), with existing data mostly derived from post-hoc analyses and small, uncontrolled observational cohorts [1-2]. We evaluated real-world persistence of advanced therapies (ATs) in FCD after TNFi failure. Methods We interrogated the Persistence Australian National IBD Cohort (PANIC), a prospectively-entered national registry of Australian prescription data. We assessed all patients receiving ATs for Crohn’s disease (CD), who had previously received TNFi for a FCD indication on a prior line of therapy. Non-persistence was defined as therapy cessation (>6 months without dispensing), and corticosteroid-free persistence as either non-persistence or corticosteroid use ≥3 months post-initiation. Kaplan-Meier curves and log-rank test assessed persistence, with propensity score matching (PSM) adjusting for baseline imbalances. Results There were 2,625 treatment lines in 1,670 patients over the 16-year period with 5,226 patient-years, using: ustekinumab (497/2,625), infliximab (837/2,625), adalimumab (1,147/2,625), and vedolizumab (144/2,625). Thiopurines and methotrexate were co-prescribed at induction in 20.2% (529/2,625) and 3.9% (103/2,625), respectively. Ustekinumab was associated with the greatest persistence, followed by infliximab, then adalimumab, and poorest persistence with vedolizumab (P<0.0001). This was unchanged when censoring ATs started <2017, and with corticosteroid-free outcomes (both P<0.0001). In subgroup analysis, for second line therapy, ustekinumab was associated with superior persistence compared with infliximab (P=0.027), vedolizumab (P=0.011), and a non-significant trend versus adalimumab (P=0.067). For ≥3rd line, ustekinumab showed greater persistence than all agents (all P<0.01). There was no persistence difference whether agents were accessed on FCD or luminal CD PBS-pathways (P=0.15). After PSM, infliximab showed superior overall- and corticosteroid-free persistence to TNFis, infliximab, adalimumab and vedolizumab (all P<0.05). Conclusion The PANIC cohort with real-world outcomes from non-hierarchical prescribing of biological-agents supports the long-term superiority of ustekinumab in FCD after TNFi failure, whilst vedolizumab shows poorest outcomes. These novel findings help guide clinicians in sequencing ATs in FCD. References: 1.Laurent P, Panaccione R, Gasink C, et al. O30 Closure of perianal fistula in patients receiving ustekinumab in the SEAVUE and STARDUST trials. Gut 2022;71:A17. 2.Feagan BG, Schwartz D, Danese S, et al. Efficacy of Vedolizumab in Fistulising Crohn’s Disease: Exploratory Analyses of Data from GEMINI 2. J Crohns Colitis. 2018 Apr 27;12(5):621-626. Conflict of interest: Chetwood, John: Speaker fees: Novartis, Eli Lilly, Dr Falk Pharma, Johnson & Johnson Paramsothy, Sudarshan: SP has served as a consultant for Vedanta Biosciences and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer