Influence of polymorphisms and TNF and IL1β serum concentration on the infliximab response in Crohn's disease and ulcerative colitis.

Aim: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are partially attributable to an increased secretion of proinflamatory cytokines, such as tumour necrosis factor (TNF) and interleukin-1β (IL1β), which play essential roles in the disease pathogenesis and are target molecules for specific therapy. Given the inter-individual variability in the response to the anti-TNF monoclonal antibody infliximab, the aim of our study was to explore the predictive value of TNF and/or IL1β as surrogate markers of infliximab response.

Methods: Serial serum concentrations of TNF and IL1β and TNF promoter region and IL1B polymorphisms were determined in 47 patients (29 CD and 18 UC) receiving infliximab and correlated with treatment response.

Results: Baseline serum concentrations of TNF and IL1β were higher in UC patients than in CD patients (p = 0.0097 and 0.0024, respectively). CD patients showing <0.64 pg/ml IL1β at baseline were more frequently responders than non-responders (p = 0.036), and the C allele of the IL1B polymorphism was associated with higher IL1β serum concentrations (p = 0.026) and with poorer clinical remission after 14 weeks of infliximab treatment. No significant association was found between serum TNF concentration or TNF polymorphism and patient response to infliximab.

Conclusion: This is the first study evaluating the pharmacogenetic role of the rs1143634 polymorphism of IL1B and TNF polymorphisms in infliximab-treated IBD patients. We found an association between the rs1143634 C allele and higher serum IL1β concentrations and a lower response to infliximab treatment in CD patients that warrants the interest of future studies in larger and independent series.