P245 Biologics Sequencing in Clinical Units (BISCUITS): Comparing outcomes in Crohn’s disease patients on second-line biologics

Abstract

Background Optimal drug sequencing for patients with Crohn’s disease (CD) who fail first line therapy with TNF-α inhibitors (TNFi) remains unclear. BISCUITS uses validated real world data from the UK IBD Registry (IBDR) to compare outcomes in CD patients who failed first line therapy with TNFi and underwent either a within-class switch (WCS) to an alternative TNFi or an out-of-class switch (OCS) to a different mechanism of action. Methods A feasibility study of 86,000 IBDR patient records identified a potential cohort of 2,678 CD patients who switched from a TNFi to a second biologic. Patients with no other prior IBD diagnosis who switched between 26/08/2015 and 31/03/2021 were included. The primary outcome was time to treatment failure after WCS or OCS, defined as days between initiation of second line (index) biologic and cessation, analysed using unadjusted Kaplan-Meier survival curves & Cox proportional-hazards models. Secondary outcomes included corticosteroid- and surgery- free drug persistence at one year (no drug stop, no steroid treatment or IBD related surgery within 365 days of index), analysed using binary logistic regression adjusting for age at index, early or later treatment with first line TNFi, primary non-response (PNR) or secondary loss of response (SLOR) to first-line TNFi, and immunomodulation therapy at index. Results An initial cohort of seven UK sites contacted, consented, and validated data for 180 patients; demographics and significant differences in case mix are shown in Table 1. Preliminary unadjusted findings suggest that OCS were less likely to discontinue index treatment compared to WCS (hazard ratio (HR): 0.64, 95% Confidence Interval (CI): 0.42 – 0.96, p = 0.03). Subgroup analysis in patients who experienced PNR to their initial TNFi indicated OCS were less likely to discontinue index treatment compared to WCS (HR: 0.25, 95% CI: 0.12 – 0.51, p < 0.001). Conversely, no significant difference in drug persistence was seen in the SLOR group (HR = 0.81, 95% CI: 0.49 – 1.36, p = 0.4), as shown in Figure 1. Binary logistic regression indicated OCS were more likely to show steroid-free drug survival at one year (adjusted odds ratio (aOR): 2.10, 95% CI: 1.10 -– 4.10, p = 0.026), surgery-free drug survival at one year (aOR = 3.31, 95% CI: 1.70 – 6.65, p < 0.001), and steroid- & surgery- free drug survival at one year (aOR = 2.14, 95% CI: 1.13 – 4.10, p = 0.02). Conclusion Real world data from this study shows overall higher drug persistence rates in OCS patients and higher steroid- and surgery- free drug survival at one year. OCS was similarly associated with significantly higher rates of drug survival in patients with PNR, but no significant difference was seen in patients with SLOR.