Treat-to-target in Crohn’s disease: Will transmural healing become a therapeutic endpoint?

Abstract

Crohn’s disease (CD) represents a chronic transmural inflammatory condition of the gastrointestinal tract, which usually leads to structural damage and significant disability. Deep remission - defined by both clinical and endoscopic remission, signifying mucosal healing - represents the current endpoint in the treat-to-target strategy, significantly improving patients’ long-term outcomes. Transmural healing (TH) could be a more effective target, but this possibility remains unclear. This narrative review aims to critically review and summarize the available literature relating TH to long-term outcomes, being the first of its kind and to the best of the author’s knowledge. A systematic literature search (from inception to March 31 2018) was performed, using multiple databases, and identifying seven full-text manuscripts. In those studies, long-term favorable outcomes (≥ 52 wk) included sustained clinical remission, as well as fewer therapeutic changes, CD-related hospitalizations, and surgeries. Despite heterogeneous design and methodological limitations, six of the studies demonstrated that TH or intestinal healing (TH plus mucosal healing) were predictive for the aforementioned favorable outcomes. Therefore, TH may become a reasonable therapeutic target and be included in the concept of deep remission. Further prospective, well-designed, multicenter trials aiming to better define the role of TH in personalized therapy for CD and to determine the long-term influence of TH on bowel damage and disability are warranted.

Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn’s Disease than Endoscopic Healing

“…There is evidence that patients who achieve transmural healing also have more favorable clinical outcomes on follow-up compared with patients who achieve EH alone. 29 It is unclear whether transmural inflammation persists in the setting of histologic healing as demonstrated on mucosal biopsies or whether achieving the potentially even deeper target of transmural healing could result in further improvement in clinical outcome compared with histologic healing alone, but this should be looked at in future research.…”

Systematic review and meta‐analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease

“…The treatment paradigm has shifted to a treat‐to‐target approach in CD in which endoscopic healing is paramount to improve remission rates and long‐term risk of complications . Despite their higher efficacy, biologics are often used as a later line of therapy for Crohn's disease (CD), after steroids, 5‐ASA or thiopurines .…”

Precision medicine for pediatric inflammatory bowel disease: a perspective

“…In IBD, we use this strategy to avoid long-term bowel damage. According to data from large-scale cohort studies and randomized controlled trials, mucosal healing or transmural healing is considered to be the potential treatment target in CD [37][38][39][40].…”