Abstract
BackgroundTrough levels of the post-induction serum infliximab (IFX) are associated with short-term and long-term responses of Crohn’s disease patients to IFX, but the inter-individual differences are large. We aimed to elucidate whether single gene polymorphisms (SNPs) within FCGR3A, ATG16L1, C1orf106, OSM, OSMR, NF-κB1, IL1RN, and IL10 partially account for these differences and employed a multivariate regression model to predict patients’ post-induction IFX levels.MethodsThe retrospective study included 189 Crohn’s disease patients undergoing IFX therapy. Post-induction IFX levels were measured and 41 tag SNPs within eight genes were genotyped. Associations between SNPs and IFX levels were analysed. Then, a multivariate logistic-regression model was developed to predict whether the patients’ IFX levels achieved the threshold of therapy (3 μg/mL).ResultsSix SNPs (rs7587051, rs143063741, rs442905, rs59457695, rs3213448, and rs3021094) were significantly associated with the post-induction IFX trough level (P = 0.015, P < 0.001, P = 0.046, P = 0.022, P = 0.011, P = 0.013, respectively). A multivariate prediction model of the IFX level was established by baseline albumin (P = 0.002), rs442905 (P = 0.025), rs59457695 (P = 0.049), rs3213448 (P = 0.056), and rs3021094 (P = 0.047). The area under the receiver operating characteristic curve (AUROC) of this prediction model in a representative training dataset was 0.758. This result was verified in a representative testing dataset, with an AUROC of 0.733.ConclusionsPolymorphisms in C1orf106, IL1RN, and IL10 play an important role in the variability of IFX post-induction levels, as indicated in this multivariate prediction model of IFX levels with fair performance.
Highlights
Infliximab (IFX), a chimeric monoclonal antibody targeting tumor necrosis factor-alpha (TNF-a), has been verified as an effective therapeutic medicine for inflammatory bowel disease (IBD) [1, 2]
We aimed to elucidate whether single gene polymorphisms (SNPs) within FCGR3A, autophagy-related 16 like 1 (ATG16L1), C1orf106, oncostatin M (OSM), oncostatin M receptor (OSMR), NF-jB1, interleukin 1 receptor antagonist (IL1RN), and interleukin 10 (IL10) partially account for these differences and employed a multivariate regression model to predict patients’ post-induction IFX levels
We aimed to elucidate whether polymorphisms within FCGR3A, ATG16L1, C1orf106, OSM, OSMR, NF-jB1, IL1RN, and IL10 are associated with IFX levels and to establish a model to predict before IFX administration the likelihood of obtaining the post-induction therapeutic IFX level !3 lg/mL
Summary
Infliximab (IFX), a chimeric monoclonal antibody targeting tumor necrosis factor-alpha (TNF-a), has been verified as an effective therapeutic medicine for inflammatory bowel disease (IBD) [1, 2]. The post-induction serum IFX trough level is associated with short-term mucosal healing [5], and effective in indicating the durable response to IFX [6,7,8]. Trough levels of the post-induction serum infliximab (IFX) are associated with short-term and long-term responses of Crohn’s disease patients to IFX, but the inter-individual differences are large. We aimed to elucidate whether single gene polymorphisms (SNPs) within FCGR3A, ATG16L1, C1orf106, OSM, OSMR, NF-jB1, IL1RN, and IL10 partially account for these differences and employed a multivariate regression model to predict patients’ post-induction IFX levels. Results: Six SNPs (rs7587051, rs143063741, rs442905, rs59457695, rs3213448, and rs3021094) were significantly associated with the post-induction IFX trough level (P 1⁄4 0.015, P < 0.001, P 1⁄4 0.046, P 1⁄4 0.022, P 1⁄4 0.011, P 1⁄4 0.013, respectively). Conclusions: Polymorphisms in C1orf106, IL1RN, and IL10 play an important role in the variability of IFX post-induction levels, as indicated in this multivariate prediction model of IFX levels with fair performance
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