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Development of a clinical model to predict secondary non-response of infliximab treatment in Crohn’s disease

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Secondary non-response to infliximab (IFX) in patients with Crohn’s disease (CD) is so common that prediction of non-response is required to adopt the optimal therapy for an individual patient.

Methods

The clinical model was constructed in a training cohort. Clinical features, serological parameters, and genetic biomarkers at week 14 IFX therapy were obtained as predictors. Secondary non-response was defined at week 54. Univariate analysis was first performed to eliminate irrelevant predictors with non-response. Then, a logistic regression model was developed by using predictors with P < 0.1 in a univariate analysis. Finally, the model was validated with reference to its discrimination, calibration, and decision curve analysis (DCA).

Results

In a univariate analysis, erythrocyte sedimentation rate (ESR), the previous surgery, disease location, C-reactive protein (CRP), and TNFRSF1B (676 T>G) were found associated with secondary non-response to IFX. Logistic regression analysis with stepwise backward selection P < 0.05 then identified that ESR, the previous surgery, CRP, and TNFRSF1B (676 T>G) could serve as independent predictors, and a clinical model was developed based on the above predictors. Model 2 with TNFRSF1B (676 T>G) incorporated demonstrated more satisfactory discrimination (P = 0.029), better calibration (U P2 > 0.05), and higher clinical value in the validation cohort.

Conclusions

The study presents a model to predict non-response to IFX in CD, which incorporates previous surgery, ESR, CRP, and TNFRSF1B (676 T>G). This model can be used to help clinicians adjust the therapeutic strategy and CD patients avoid unnecessary exposure to IFX.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160# Pu Jian Ave, Shanghai, 200127, China

    Lijun Xu, Jun Shen & Qing Zheng

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  1. Lijun Xu
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  2. Jun Shen
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Contributions

LX performed the statistical procedure and draft the article. JS designed this study, and QZ helped edit the manuscript. The final version of the manuscript was approved by all authors.

Corresponding authors

Correspondence to Jun Shen or Qing Zheng.

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The authors declare that they have no conflict of interest.

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This study was approved by the ethics review board in Renji Hospital, School of Medicine, Shanghai Jiao Tong University.

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Xu, L., Shen, J. & Zheng, Q. Development of a clinical model to predict secondary non-response of infliximab treatment in Crohn’s disease. Int J Colorectal Dis 35, 2019–2026 (2020). https://doi.org/10.1007/s00384-020-03679-8

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