EP660 - Association of SNPs with Biologic Use Progression in IBD Surgery

Purpose/Background: Despite the increasing use and availability of biologic medications for the management of IBD, tailoring use lacks data-driven guidelines. This paucity of data makes selection of any particular biologic challenging as individuals may cycle through multiple medications as they develop recrudescent disease or side effects related to these medications. We therefore sought to leverage our institutional IBD biobank to correlate clinical responses to different classes of biologic medications with a selected panel of IBD-related SNPs.

Methods/Interventions: Patients with UC, CD, or indeterminate colitis with available sequencing data in our institutional biobank who used at least one biologic were included. We examined details regarding biologic use duration, sequence, and reason for discontinuation of therapy. Patients were categorized as responders or non-responders to particular biologic classes: TNF agents, interleukin targeting agents, integrin targeting agents, and JAK inhibitors. A panel of SNPs related to IBD was then analyzed to correlate with baseline clinical characteristics and response to biologic classes. Phenotype data were recoded into binary outcomes (e.g., TNF response) and genotype strings converted to an additive numeric model after filtering for missingness. Logistic regression models, adjusted for disease type, sex, and surgery, were run for each SNP against outcomes, and SNPs with p < 0.05 were further annotated.

Results/Outcomes: 165 patients in our institutional IBD biobank were included. 91 (55%) were female and 98 (59%) had UC. We focus on two primary analyses: Responsiveness to any biologic, and responsiveness to TNF therapy in particular. For the former, we report the most robust associations with SNPs in genes HRP, MTF1, FCRL3; genes related to the innate immune system and autoimmunity. For the latter, we identify associations in ATG16L1, a regulator of autophagy, and CDC14C, a phosphatase with a role in cell turnover.

Conclusion/Discussion: SNPs as pharmacogenetic tools are currently underutilized for prognostication of responses to biologics in IBD. Here we report enriched SNPs in relation to clinical responses to various classes of biologic medications. The identified genes have clinical relevance to the immune system and autophagy; presenting possible inroads for further exploration of the specific mechanisms that yield responsiveness to specific biologics.
While data presented here are not robust enough to provide clinical recommendations for biologic selection, they represent a foray into more tailored medical therapy in an increasingly complex clinical landscape in a notoriously heterogenous disease. We hope to further explore these SNPs and related pathways both as prognostic biomarkers and functional targets for the personalized management of IBD.