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Single nucleotide polymorphisms in TNF receptor superfamily (TNFRSF) 1A and 1B, and Fas ligand genes, have been associated with responsiveness to infliximab in Crohn's disease.
Dr Steenholdt and colleagues from Denmark investigated if SNPs in TNF receptor superfamily 1A and 1B, and FAS (TNFRSF6) and Fas ligand (TNFSF6), associated with short- or long-term clinical and biological efficacy and with acute severe infusion reactions.
Observational, retrospective and explorative cohort study of infliximab-treated Caucasian patients with Crohn's disease classified as primary nonresponders, response failures on maintenance therapy, maintained remission, and occurrence of acute severe infusion reactions. During infliximab maintenance therapy, minor allele carriage of TNF receptor superfamily 1B, rs976881 is associated with loss of response.  | | The minor allele of Fas ligand, rs76110 increased risk of severe infusion reactions | | Alimentary Pharmacology & Therapeutics |
The research team found that minor allele homozygosity increased the risk substantially, and furthermore associated with a mean CRP increase of 17 mg/L as compared to a mean decrease of 17 mg/L in all others. In contrast, the team noted that minor allele carriage of TNF receptor superfamily 1B, rs1061622 is associated with beneficial response to infliximab induction, and with persistence of remission during maintenance therapy. The researchers found that carriage of the minor allele of Fas ligand, rs76110 increased risk of severe infusion reactions. The team noted that minor allele carriage of TNF receptor superfamily 1B, rs652625 decreased the risk.
Dr Steenholdt's team commented, "The TNF receptor superfamily 1B polymorphisms may contribute to predict efficacy of infliximab." "Moreover, Fas ligand and TNF receptor superfamily 1B polymorphisms may confer genetic susceptibility to severe infusion reactions." "These findings could potentially aid clinical decisions if confirmed in larger studies."
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