Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort

Abstract

Adalimumab; Infliximab; Pharmacogenetics

Adalimumab; Infliximab; Farmacogenètica

Adalimumab; Infliximab; Farmacogenética

The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.

This research was funded by Instituto de Salud Carlos III, grant number PI19/00792 (L.A.L.-F.) and Juan Rodes program JR19/00005 (E.L.-M.), by Instituto de Investigación Sanitaria Gregorio Marañón, grant number 2021-II-postdoc-01 (S.S.-M.), and by Consejería de Educación, Universidades, Ciencia y Portavocía Comunidad de Madrid, grant number PEJ-2021-AI/BMD-21866 (P.Z.-C.). The study was co-funded by the European Union.