Objective:To investigate the risk factors and establish a prediction model of primary non-response (PNR) to anti-tumor necrosis factor-α(TNF-α) monoclonal antibody in Crohn′s disease (CD) patients.Methods:From December 1, 2018 to July 31, 2022, 103 patients with CD treated with the anti-TNF-α monoclonal antibody in Renmin Hospital of Wuhan University were enrolled (modeling group), and at the same time, 109 patients with CD treated with anti-TNF-α monoclonal antibody in Zhongnan Hospital of Wuhan University were selected (validation group). The baseline clinical data of all the patients before the first treatment of anti-TNF-α monoclonal antibody were collected, which included C-reactive protein (CRP), the simplified Crohn′s disease activity index (CDAI), and modified multiplier simple endoscopic score for Crohn′s disease (MM-SES-CD), etc. Multivariate logistic regression was used to screen the independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody, and to establish the nomograms prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), the net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA) were used to evaluate the predictive efficacy and clinical application value of the prediction model. DeLong test was used for statistical analysis.Results:The results of multivariate logistic regression analysis showed that high level of CRP ( OR=1.030, 95% confidence interval (95% CI) 1.002 to 1.059), simplified CDAI ( OR=1.399, 95% CI 1.023 to 1.913), and MM-SES-CD ( OR=1.100, 95% CI 1.025 to 1.181) in baseline were independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody ( P=0.033, 0.036 and 0.008). The results of ROC analysis showed that the AUCs of CRP, simplified CDAI, MM-SES-CD, and the prediction model in the modeling group and the validation group were 0.697(95% CI 0.573 to 0.821), 0.772(95% CI 0.666 to 0.879), 0.819(95% CI 0.725 to 0.912), 0.869 (95% CI 0.786 to 0.951) and 0.856 (95% CI 0.756 to 0.955), respectively. The AUC of the prediction model in the modeling group was greater than those of CRP and simplified CDAI, and the differences were statistically significant ( Z=3.00 and 2.75, P=0.003 and 0.006), while compared with MM-SES-CD and the validation group, the differences were not statistically significant (both P>0.05). However, compared with MM-SES-CD, the NRI and IDI of the prediction model in the modeling group were 0.205(95% CI 0.002 to 0.409, P=0.048) and 0.098(95% CI 0.022 to 0.174, P=0.011), respectively, suggesting that the predictive ability of the prediction model was better than that of MM-SES-CD. The results of DCA indicated that the prediction model had significant clinical benefits in both the modeling group and the validation group. Conclusions:A prediction model was successfully constructed based on the independent risk factors for PNR in patients with CD treated with the anti-TNF-α monoclonal antibody. After verification, the prediction model has good prediction performance and significant clinical benefits.