Correlation of infliximab related genetic polymorphism, serum trough concentration and efficacy in patients with Crohn's disease / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the correlations of genetic polymorphisms, infliximab(IFX) serum trough concentration, immunogenicity and clinical outcome in patients with Crohn's disease(CD) to provide reference for optimizing IFX treatment in CD patients. METHODS: The clinical data of CD patients treated with IFX in our hospital from September 2017 to September 2019 were prospectively collected. The genotypes TNF-α-308, TNF-α-238, TNF-α-857, TNFRSF1B, ABCB1, FCGR3A were detected by targeted sequencing using multiple PCR combined with high throughput sequencing before administration. The IFX steady-state concentration was determined by ELISA. SPSS 20.0 software was used for statistical analysis and ROC curve was drawn for clinical efficacy and antibody threshold. RESULTS: A total of 111 patients were included in the study, the IFX trough concentration of patients with TNF-α-238GA was significantly lower than that of GG (0.55±0.52) vs. (1.75±1.46) μg/mL (P=0.003), while there was no significant difference in IFX trough concentration among TNF-α-308, TNF-α-857, TNFRSF1B, ABCB1, FCGR3 Agenotypes. Clinical response rate of TNFRSF1B (TG+GG) was significantly higher than that of the wild type (TT) (75.0% vs. 42.3%) (P=0.001), and there was no statistically significant difference in clinical efficacy among patients with different genotypes of other genes (P>0.05). The efficacy of IFX in the treatment of CD and the production of antibody to IFX were significantly correlated with maintenance trough concentration (P1.33 μg/mL had certain predictive significance for biological response, while ≤0.51 μg/mL can be used as a predictor of antibody production.