Treat to Target: The Role of Histologic Healing in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis

Clin Gastroenterol Hepatol. 2021 Sep;19(9):1800-1813.e4. doi: 10.1016/j.cgh.2020.09.046. Epub 2020 Sep 30.


Background: Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies.

Methods: We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined.

Findings: Our meta-analysis included 28 studies contributing 2,806 patients (2677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR, 2.41; 95% CI, 1.91-3.04), with a similar effect noted in the subgroup with endoscopic Mayo endoscopic score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates-Geboes <3.1 (OR, 2.40; 95% CI, 1.57-3.65), Geboes <2.1 (OR, 3.91; 95% CI, 2.21-6.91) and Geboes 0 (OR, 7.40; 95% CI, 2.00-18.27). Among individual histologic features, basal plasmacytosis (OR, 1.94), neutrophilic infiltrations (OR, 2.30), mucin depletion (OR, 2.05), and crypt architectural irregularities (OR, 2.22) predicted relapse. There was no association between histologic activity and relapse in CD.

Conclusions: In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact.

Keywords: Histologic Healing; Relapse; Ulcerative Colitis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Colitis*
  • Colitis, Ulcerative*
  • Crohn Disease*
  • Humans
  • Inflammatory Bowel Diseases*
  • Remission Induction