One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study

Abstract

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe in ammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show optimal response to induction therapy, while others lose their response over time, for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated serum concentrations of in iximab, adalimumab and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and in ammation on anti-TNFα response. We found a signi cant association between the SNP in TNFα promoter (-308G > A) and clinical remission without steroids in patients on in iximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

Genetic Variants Associated with Biological Treatment Response in Inflammatory Bowel Disease: A Systematic Review

“…A large proportion of these SNPs have been located in key cellular pathways, knowledge of which is of great importance in selecting the most effective therapeutic intervention to improve IBD management [50,51]. This is the case for anti-TNFα, which is employed extensively for moderate to severe IBD, although not all patients show an optimal response to induction therapy, and, for others, the response fails over time for unknown reasons [52].…”