Background: Mucosal healing (MH) is currently accepted as the optimal target in Crohn's disease (CD), and is associated with improved long-term outcomes including reduced hospitalizations and surgery. However, even in patients with sustained MH, residual transmural inflammation may persist. The benefits of obtaining complete transmural healing (TH) have not been previously assessed. The aim of the study was to evaluate the long-term outcomes of TH in CD.
Methods: This was a multicenter observational study including patients from a prospective database of Inflammatory bowel disease (Grupo de Estudos de Doença Inflamatόria Intestinal). Patients with CD with a MRI-enterography (MRE) and colonoscopy performed in a 6-month interval were included. MRE was classified as active/inactive based on abnormal bowel wall thickening, contrast enhancement, fat creeping, Comb sign, and complications (stricture, abscess or fistula). In non-operated patients, colonoscopy was classified as active/inactive based on the presence of ulceration. In operated patients, colonoscopy was classified as active/inactive if the Rutgeerts score was ≥i2. We defined 3 groups: TH (inactive MRE with inactive colonoscopy); MH (active MRE with inactive colonoscopy), No healing (NH) (active colonoscopy). We evaluated several outcomes at 1 year including the need for surgery, hospital admission, therapy escalation (immunomodulator, biologic or escalation of biologic), and a compound outcome including any of the former. Patients with disease restricted to the colon were excluded.
Results: A total of 214 patients [TH (n=33), MH (n=52), NH (n=129)], 91 (41.7%) previously operated, were included in the study. MRE and colonoscopy showed active inflammation in 162 (74.3%) and 132 patients (60.6%), respectively. At 12 months, patients with TH showed lower rates of hospital admission than patients with MH and NH (6.1% vs 17.3%, p=0.188 (ns) and 24.0%, p=0.014), therapy escalation (15.2% vs 36.5%, p=0.027 and 54.3%, p<0.001), surgery (0% vs 11.5%, p=0.047 and 11.6%, p=0.027), and any outcome (18.2% vs 44.2%, p=0.011 and 63.6%, p<0.001). Patients with TH showed longer times to surgery (p=0.045 and p=0.044 for MH and NH), therapy escalation (p=0.046 and p<0.001 for MH and NH), and to reach any endpoint (p=0.019 and p<0.001 for MH and NH). Increasing age (OR 0.971, 95% CI [0.951–0.992], p=0.006), MH (OR 0.384, 95% CI [0.208–0.707], p=0.002), and TH (OR 0.336, 95% CI [0.171–0.660, p=0.002] were independently associated with a lower likelihood of reaching the compound outcome.
Conclusions: TH is associated with improved long-term outcomes in patients with CD, including lower risk of hospital admission, therapy escalation and surgery. Our data suggests that TH is a better suitable target than MH in CD.