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

Table 3 Outcomes of patients achieving transmural healing and intestinal healing

First author, year, country	Long-term CR; percentage; other findings	Change in medication	Reduction in hospitalizations for active CD	Reduction in CD-related surgery	Other findings/Comments	Limitations
Eder, 2016, Czech Republic[42]	38%; TH: not useful for predicting long-term CR IH: predicts long-term CR, P = 0.02 (75% Sen, 72% Spe)	N/A	N/A	N/A	MH: borderline significance (P = 0.06) in predicting long-term CR (50% Sen, 80% Spe)	RS, Low number of patients, Only ileocolonic CD, No MRE, No IC by the end of 1 yr therapy
Sauer, 2016, United States[43]	TH: 88.9% vs 44.6% of those with MRE active inflammation (no TH), P < 0.001	TH: 8.3% vs no TH: 44.6% (switching from IMD to biologic and changing type of biologic, P < 0.001)	N/A	TH: 2.8% vs No TH: 18.5%, P = 0.024	N/A	RS, All MRE - part of patient care, No standardized MRE score, No MRE, No IC at end of follow-up
Deepak, 2016, United States[14]	N/A	Complete or partial radiologic response decreases risk for CS use by over 50% [HR: 0.37 (95%CI: 0.21-0.64), P < 0.001 and 0.45 (95%CI: 0.26-0.79), P = 0.005 respectively]	Complete response decreases risk of hospitalizations by over two-thirds [HR: 0.28 (95%CI: 0.15-0.50), P < 0.001]; also partial response decreases risk [HR: 0.54; (95%CI: 0.32-0.92), P = 0.04]	Complete response decreases risk of surgery by over two-thirds [HR: 0.34 (95%CI: 0.18-0.63)], P < 0.001	First data to demonstrate the magnitude and significance of radiological response as a treatment target and endpoint; Penetrating behavior is a risk for hospitalization for active disease and shows a trend towards increased surgical risk	RS Tertiary referral center Not all IC available
Fernandes, 2017, Spain[13]	N/A	IH: less therapy escalation vs MH and vs NH (15.2% vs 36.5%, P = 0.027 and vs 54.3%, P < 0.001); IH: longer time until therapy escalation vs MH, P = 0.046 and vs NH, P < 0.001; MH better outcome than NH	IH: hospitalization rate lower vs MH and vs NH (3.0% vs 17.3%, P = 0.044 and vs 24.0%, P = 0.003); no difference MH vs NH IH: time until hospital admission longer vs MH, P = 0.046 and vs NH, P = 0.008	IH: surgery rates lower vs MH and vs NH (0% vs 11.5%, P = 0.047 and vs 11.6%, P = 0.027); no difference MH vs NH IH: longer time to surgery vs MH (P = 0.045) and vs NH (P = 0.044)	Endoscopic remission (OR: 0.331, 95%CI: 0.178-0.614, P < 0.001) and MRE remission (OR: 0.270, 95%CI: 0.130-0.564, P < 0.001): independently associated with a lower likelihood of reaching any of the studied outcomes	RS, dichotomous definition of IH and MH, No scores, No patients with stenosis, Interval between IC and MRE (up to 6 mo) Only baseline IC and MRE
Ripollés, 2016, Spain[41]	Good sonographic response at 52 wk predicts good long-term clinical outcome (2-3 yr) with a Sen of 78% and Spe of 81.3%; OR: 15.5	TH at 52 wk: 93% did not require change in medication/surgery	N/A	TH/sonographic improvement at 52 wk: less likely to require change/intensification in MD or surgery during follow-up vs no improvement (11% vs 65%, P < 0.001)	Changes in BWT: most important in assessment of the effects of therapy; 42% of patients without complications achieved TH vs only 5% with complicated behavior; Initial stricture: the only sonographic feature predictive for negative response (P = 0.0001)	No IC, No validated US-based activity score
Orlando, 2018, Italy[44]	N/A	N/A	Hospitalization rate decreases significantly with an increase in the number of parameters indicating remissions at baseline	Significant less surgery in patients with a strain ratio < 2 at baseline (P = 0.009)	No association between baseline BWT at US and therapeutic outcomes	Low number of patients, No IC, Single center study
Laterza, 2018, Italy[15]	N/A	Complete remission vs patients with one or two remissions (partial remission) vs no remission: differences among groups different only for the need of topical CS (P = 0.03)	Complete remission (CR, MH, TH): trend for fewer hospitalizations vs patients with only MH or TH or CR	N/A	Endoscopic remission: significantly less changes in therapy vs endoscopic activity (P = 0.02) Multiparametric (CR, MH, and TH) evaluation might have a better value to predict significant changes in therapy and hospitalization	Heterogeneous therapies CTE: qualitative non-validated score Only baseline clinical, IC and CTE evaluation

BWT: Bowel wall thickness; CD: Crohn’s disease; CFREM: Clinical CS-free remission; CR: Clinical remission; CS: Corticosteroids; CTE: Computed tomography enterography; IC: Ileocolonoscopy; IH: Intestinal healing; IMD: Immunomodulators; MD: Medication; MH: Mucosal healing; MRE: Magnetic resonance enterography; N/A: Not available; NH: No healing; RS: Retrospective study; Sen: Sensitivity; Spe: Specificity; TH: Transmural healing.