Early Prediction of Primary Non-Response to Infliximab in Crohn's Disease Using Routinely Available Clinical and Week 2 Laboratory Indicators: A Two-Center Real-World Cohort Study.

PURPOSE: Primary non-response (PNR) occurs in a subset of patients with Crohn's disease (CD) after infliximab (IFX) induction therapy and remains challenging to identify early. This study aimed to develop and perform preliminary external validation of an early PNR risk stratification model using routinely available clinical and Week 2 laboratory indicators. PATIENTS AND METHODS: This two-center real-world retrospective cohort study included patients with CD receiving IFX induction therapy from January 2019 to September 2025. Center 1 served as the derivation cohort and Center 2 as the external validation cohort. Model 2C, incorporating complicated disease behavior, Week 2 C-reactive protein (CRP), and Week 2 albumin, was developed using multivariable logistic regression. Model performance was assessed using discrimination, calibration, and overall prediction accuracy. Bootstrap internal validation was performed in the derivation cohort, and the model formula and prespecified fixed cutoff were applied unchanged to the external validation cohort. RESULTS: Among 201 patients, 63 experienced PNR and 138 did not. The derivation and external validation cohorts included 125 and 76 patients, respectively; complete-case analyses of Model 2C included 120 and 76 patients. Higher Week 2 CRP and lower Week 2 albumin were associated with increased PNR risk. In the derivation cohort, Model 2C showed an apparent AUC of 0.814 and a bootstrap-corrected AUC of 0.797. In the external validation cohort, discrimination remained good (AUC, 0.888), but calibration was suboptimal, with a calibration slope of 0.662 and an observed-to-expected ratio of 0.713, indicating systematic risk overestimation (observed event rate, 34.2%; mean predicted risk, 48.0%). Using the prespecified cutoff of 0.2175, the low-risk group had a PNR rate of 3.4% and a negative predictive value of 96.6%. CONCLUSION: Model 2C provides an exploratory approach for early PNR risk stratification during IFX induction therapy, particularly for identifying patients at lower risk of PNR. However, it should not be interpreted as a tool for individual absolute-risk prediction or used as a standalone basis for treatment intensification or switching. Further multicenter prospective validation, recalibration assessment, and clinical-impact studies are required.