P818 Polymorphisms in C1orf106, IL1RN, IL10 are associated with postinduction infliximab trough level in Crohn's disease patients
J. Tang*1, C. Zhang2, X. Wang2, X. Gao1
1The Sixth Affiliated Hospital of Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, China, 2Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
The post induction serum infliximab trough concentration was associated with short-term and long-term response to infliximab (IFX), but it has large interindividual difference.
The present study investigated the effects of genetic (polymorphisms within FCGR3A, ATG16L1, C1orf106, OSM, OSMR, NF-κB1, IL1RN, IL10) and nongenetic (sex, weight, baseline albumin and combination therapy) factors on IFX therapeutic threshold (3 μg/ml) after 14 weeks-induction therapy.
We found that rs7587051, rs143063741, rs442905, rs59457695, rs3213448 and rs3021094 were found to be significantly associated with the post induction IFX trough level (
Genotype in response to infliximab level in patients. Results of 6 SNPs as showed (a) to (f). Mann–Whitney U-test.
Using multi-variate logistic regression analysis, baseline albumin and SNPs within C1orf106, IL1RN, IL10 were included in the multi-variate prediction model (AUROC = 0.758) with p values of 0.002, 0.025, 0.049, 0.056 and 0.047 for baseline albumin, rs442905, rs59457695, rs3213448 and rs3021094, respectively. The sensitivity and specificity of this prediction model was 60.27% and 83.05%, respectively. This result was verified in a testing dataset with AUROC of 0.733.
ROC curve analysis the performance of multi-variate Logistic regression model on training datasets and testing datasets.
Serum albumin level and polymorphisms in C1orf106, IL1RN, IL10 play important role in the variability of IFX post induction level and should be measured before IFX administration. Through the prediction model, the patients who might fail to achieve IFX therapeutic threshold could be found in advance and dose intensification in the future might be needed for them.