Infliximab and adalimumab in the treatment of fistulizing Crohn's disease: a propensity score-matched analysis from the prospective Persistence Australian National IBD Cohort (PANIC4) study.

Background/aims: There are spare data on comparative medication efficacy in fistulizing Crohn's disease (FCD), particularly with immunomodulator co-therapy. Persistence is a unique way to assess real-world outcomes.

Methods: The persistence of all dispensed biological agents were analysed from the Australian Pharmaceutical Benefits Scheme (PBS) registry data 2005-2021 for FCD. Propensity score matching was performed to account for baseline cohort imbalance.

Results: There were 5,739 lines of therapy in 4,466 patients over the 16-year period with 17,144 patient-years of follow-up; via therapy 2,605/5,739 (45.4%) used adalimumab and 3,134/5,739 (54.6%) used infliximab; 1,697/5,739 (29.6%) used thiopurine co-therapy at induction, whilst 242/5,739 (4.2%) used methotrexate. As a first-line biologic (biologic-naïve), infliximab showed superior overall- and corticosteroid-free persistence to adalimumab (P=0.0002 and P=0.0021 respectively). Used after first-line (biologic-exposed), there was no difference between agents for overall persistence (P=0.064) though infliximab showed greater corticosteroid-free persistence (P=0.030). Co-induction with thiopurine was associated with improved overall- and corticosteroid-free persistence (P=0.0002 and P=0.045 respectively). After propensity score matching, infliximab showed superior overall and corticosteroid-free persistence compared to adalimumab in bio-naïve (P<0.0001 and P=0.0016 respectively), not in bio-exposed patients (P=0.12 and P=0.074 respectively). Thiopurine was associated with superior overall- and corticosteroid-free persistence use, though no difference was seen with methotrexate.

Conclusion: The PANIC cohort with real-world data of non-hierarchical prescribing of biological agents supports the superiority of infliximab over adalimumab in bio-naïve FCD patients, but did not show a therapeutic difference in bio-exposed FCD. Thiopurine co-therapy was independently associated with improved biological agent persistence in FCD.