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

Table 2 Definitions used in the included studies

First author, year, country	CR definition; percentage	MH: definition; percentage, timing	Cross-sectional imaging method (details)	TH (± IH): definition	Percentage of TH, timing	Agreement MH-TH
Eder, 2016, Czech Republic[42]	CDAI < 150	MH: ≥ 50% decrease in SES-CD; 62%, after induction	MRE (score: SEAS-CD)	TH: ≥ 50% decrease in SEAS-CD IH: TH + MH: ≥ 50% decrease in both SES-CD and SEAS-CD	TH: 38%, IH: 31%, both after induction	N/A
Sauer, 2016, United States[43]	According to PGA	No IC	MRE (no score; "all or none" approach - abnormal BWT, increased enhancement)	TH: lack of active inflammation, complete MRE healing (normal BWT and no increased enhancement)	TH: 35.6%, at inclusion	N/A
Deepak, 2016, United States[14]	N/A	Inactive IC; 17.3%, at 2nd CTE/MRE (data missing in 61% of patients)	MRE/CTE (score by[37]): BWT ≥3 mm, mural hyperenhancement, or intramural hyperintense T2 signal; segments length; comb sign, peri-enteric inflammation (absent, localized edema, inflammatory mass, abscess), fistula, stricture	TH: reduction in lesion length to 0 cm and a score < 1 for all other parameters (decreased enhancement or length of disease, no worsening of parameters of active inflammation - dilated vasa recta/comb sign, perienteric inflammation (edema, phlegmon, or abscess), or fistula	Complete radiologic responders: 37%, at 2nd CTE/MRE	Of inactive ileum at IC: 46% with active disease at 2nd CTE/MRE
Fernandes, 2017, Spain[13]	N/A	Inactive IC: no mucosal ulceration; in operated patients - Rutgeerts score 0-1; Inactive IC: 39.4% MH group = inactive IC + active MRE: 24.3%	MRE (active: BWT > 3 mm, increased contrast enhancement, and complications - stricture, abscess, or fistulae; additionally: fat creeping and comb sign)	IH (TH) group: MH + inactive MRE NH: active endoscopy, irrespective of the MRE findings	Inactive MRE: 25.7% IH group: 15.4% NH group: 60.3%	Significant low correlation between inflammation assessed by MRE and IC (Spearman’s rho = 0.244, P < 0.001)
Ripollés, 2016, Spain[41]	HBi < 5 and normal CRP, without CS	No IC	US/CEUS (sonographic score: transmural inflammation - BWT, color Doppler grade, mural enhancement; extramural involvement, and obstructive disease)	TH: BWT < 3 mm, besides color Doppler grade 0 and the absence of complications, regardless of the persistence of parietal enhancement	TH: 14%, at 12 weeks and 30%, at 52 wk	N/A
Orlando, 2018, Italy[44]	N/A	No IC	US/UEI (bowel wall stiffness: strain ratio between mesenteric tissue and bowel wall; strain ratio ≥ 2 = severe ileal fibrosis	TH: BWT ≤ 3 mm	TH at 14 and 52 wk: 27% and 30%, respectively. Baseline strain ratio: lower in those with TH (P < 0.05)
Laterza, 2018, Italy[15]	HBi ≤ 4; 56% at baseline	MH: SES-CD ≤ 2; 19%, at baseline	CTE (qualitative judgment on transmural activity, based on lesions: BWT, stenosis, target sign, comb sign, lymphadenopathy, fistula, abscess, sinus tract, fibrofatty proliferation, perienteric stranding, free fluid in the abdomen)	TH: absence of typical CTE lesions	TH: 17.5%, at baseline	Agreement between CTE and IC in 47% (k = – 0.05; P = 0.694); Agreement between CTE, IC and HBi in 18% (k = 0.01; P = 0.41), TH: detected in 27% with MH

BWT: Bowel wall thickness; CD: Crohn’s disease; CDAI: Crohn’s disease activity index; CEUS: Contrast-enhanced ultrasonography; CR: Clinical remission; CRP: C-reactive protein; CTE: Computed tomography enterography; HBi: Harvey-Bradshaw index; IC: Ileocolonoscopy; IH: Intestinal healing; MH: Mucosal healing; MRE: Magnetic resonance enterography; N/A: Not available; NH: No healing; PCDAI: Pediatric-CD activity index; PGA: Physician global assessment; SEAS-CD: Simple enterographic activity score for CD; SES-CD: Simple endoscopic score in CD; TH: Transmural healing; UEI: Ultrasound elasticity imaging; US: Ultrasonography.