Multi-alleles predict primary non-response to infliximab therapy in Crohn's disease

Background: Infliximab (IFX) is the first-line treatment for patients with Crohn's disease (CD) and is noted for its relatively high cost. The therapeutic efficacy of IFX has noticeable individual differences. Known single-gene polymorphisms (SNPs) are inadequate for predicting non-response to IFX. In this study, we aimed to identify new genetic factors associated with IFX-therapy failure and to predict non-response to IFX by developing a multivariate predictive model.

Methods: In this retrospective study, we collected and analysed the data of Chinese patients with CD who received IFX therapy at one hospital between June 2013 and June 2019. Primary non-response (PNR) and non-durable response (NDR) were evaluated using a simple endoscopic score for CD (SES-CD). A total of 125 SNPs within 44 genes were genotyped. A multivariate logistic-regression model was established to predict non-response to IFX. An area-under-the-receiver-operating-characteristics curve (AUROC) was applied to evaluate the predictive model performance.

Results: Forty-two of 206 (20.4%) patients experienced PNR and 15 of 159 (9.4%) patients experienced NDR. Nine SNPs were associated with PNR (P < 0.05). A PNR predictive model was established, incorporating 2-week high-sensitivity C-reactive protein (hs-CRP), rs61886887, rs61740234, rs357291, rs2269330, and rs111504845, and the AUROC on training and testing data sets were 0.818 (P < 0.001) and 0.888 (P < 0.001), respectively. At week 14, hs-CRP levels ≥ 2.25 mg/L were significantly associated with NDR (AUROC = 0.815, P < 0.001). PNR-associated SNPs were not mutually associated with NDR, suggesting distinct mechanisms between PNR and NDR.

Conclusion: Genetic polymorphisms are significantly associated with response to IFX among Chinese CD patients.