Risk Prediction and Comparative Efficacy of Anti-TNF vs Thiopurines, for Preventing Postoperative Recurrence in Crohn's Disease: A Pooled Analysis of 6 Trials

Clin Gastroenterol Hepatol. 2022 Dec;20(12):2741-2752.e6. doi: 10.1016/j.cgh.2021.10.021. Epub 2021 Oct 20.

Abstract

Background & aims: The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification.

Methods: After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines.

Results: In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33-0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26-0.96), and severe ER (RR, 0.41; 95% CI, 0.21-0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups.

Conclusions: Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.

Keywords: Adalimumab; Azathioprine; Ileocecal; Inflammatory Bowel Disease; Infliximab; Mercaptopurine; Resection.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Crohn Disease* / drug therapy
  • Crohn Disease* / prevention & control
  • Crohn Disease* / surgery
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Neoplasm Recurrence, Local
  • Postoperative Period
  • Recurrence
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha
  • Immunosuppressive Agents