Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease

Background: Clinical manifestations of Crohn's disease (CD) do not reliably correlate with endoscopic activity. While treating to achieve clinical remission (CR) has neither proven to improve CD outcomes nor alter the natural disease course, it is unclear whether targeting objective measures like mucosal healing (MH) is associated with improved long-term outcomes.

Aim: To perform a systematic review and meta-analysis comparing long-term outcomes in active CD patients who achieve MH compared to those who do not.

Methods: We performed a systematic literature search to identify studies with prospective cohorts of active CD patients that included outcomes of patients who achieved MH at first endoscopic assessment (MH1) compared to those who did not. The primary outcome was long-term (≥50 weeks) CR. Secondary outcomes included CD-related surgery-free rate, hospitalisation-free rate and long-term MH rate. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated.

Results: Twelve studies with 673 patients met inclusion criteria. Patients achieving MH1 had a pooled OR of 2.80 (95%CI, 1.91-4.10) for achieving long-term CR, 2.22 (95%CI, 0.86-5.69) for CD-related surgery-free rate, and 14.30 (95%CI, 5.57-36.74) for long-term MH. Sensitivity analyses suggested no difference in outcomes if MH1 was achieved on biologics vs. non-biologics. No significant publication bias or heterogeneity was detected.

Conclusions: Achieving MH1 is associated with increased rates of long-term clinical remission, and maintenance of mucosal healing in active Crohn's disease and may therefore be a reasonable therapeutic target.