Therapeutic Advances in Gastroenterology (May 2024)

Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn’s disease

  • Liang Chen,
  • Dengfeng Kang,
  • Leilei Fang,
  • Mingming Sun,
  • Mingsong Li,
  • Guangxi Zhou,
  • Chunjin Xu,
  • Zhi Pang,
  • Yulan Ye,
  • Baisui Feng,
  • Huili Wu,
  • Jian Lin,
  • Baijing Ding,
  • Changqin Liu,
  • Yanhong Shi,
  • Zhanju Liu

DOI
https://doi.org/10.1177/17562848241256237
Journal volume & issue
Vol. 17

Abstract

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Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn’s disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn’s disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD ( p < 0.001), CDAI ( p < 0.001), and C-reactive protein (CRP) ( p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.