Correlation of infliximab related genetic polymorphism, serum trough concentration and efficacy in patients with Crohn's disease
10.12092/j.issn.1009-2501.2020.09.006
- VernacularTitle: 克罗恩病患者英夫利西单抗相关基因多态性与血药浓度及疗效关联性研究
- Author:
Rongfang LIN
1
Author Information
1. Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University
- Publication Type:Journal Article
- Keywords:
Clinical efficacy;
Crohn's disease;
Genetic polymorphism;
Infliximab;
Serum trough concentration
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(9):1000-1006
- CountryChina
- Language:Chinese
-
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 (P<0.01). The optimal IFX trough concentration thresholds for predicting CPR≤5 mg/L and clinical response after treatment were 1.33, 0.85 μg/mL, respectively. Trough concentration ≤0.51 μg/mL was used as an indicator to predict the generation of antibody. CONCLUSION: Polymorphisms of TNF-α-238 and TNFRSF1B can affect the maintenance trough concentration and clinical response of IFX in CD patients, respectively. The trough concentration at IFX maintenance stage >1.33 μg/mL had certain predictive significance for biological response, while ≤0.51 μg/mL can be used as a predictor of antibody production.
