Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease.

Background High inter-individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine-induced myelosuppression, thiopurine-induced pancreatitis and immunogenicity of Tumour Necrosis Factor alpha (TNF alpha) antagonists have been identified, but uptake of pre-treatment pharmacogenetic testing into clinical guidelines has been slow. Aim To explore the efficacy of a pharmacogenetic passport for IBD that includes multiple pharmacogenetic predictors of response. Methods Patients with IBD exposed to thiopurines and/or TNF alpha antagonists were retrospectively evaluated for the presence of thiopurine toxicity and/or immunogenicity of TNF alpha antagonists. All patients were genotyped using both whole-exome sequencing and the Illumina Global Screening Array. An in-house-developed computational pipeline translated genetic data into an IBD pharmacogenetic passport that predicted risks for thiopurine toxicity and immunogenicity of TNF alpha antagonists per patient. Using pharmacogenetic-guided treatment guidelines, we calculated clinical efficacy estimates for pharmacogenetic testing for IBD. Results Among 710 patients with IBD exposed to thiopurines and/or TNF alpha antagonists, 150 adverse drug responses occurred and our pharmacogenetic passport would have predicted 54 (36%) of these. Using a pharmacogenetic passport for IBD that includes genetic variants predictive of thiopurine-induced myelosuppression, thiopurine-induced pancreatitis, and immunogenicity of TNF alpha antagonists, 24 patients need to be genotyped to prevent one of these adverse drug responses. Conclusions This study highlights the clinical efficacy of a pharmacogenetic passport for IBD. Implementation of such a pharmacogenetic passport into clinical management of IBD may contribute to a reduction in adverse drug responses.