Copyright
©The Author(s) 2018.
World J Clin Cases. Oct 26, 2018; 6(12): 501-513
Published online Oct 26, 2018. doi: 10.12998/wjcc.v6.i12.501
Published online Oct 26, 2018. doi: 10.12998/wjcc.v6.i12.501
Table 1 Characteristics of the included studies
| First author, year, country | Study type | CD population, disease location, behavior, surgery | Duration of CD in yr | MD | Aim of study | Methods used to assess CD activity, timing | Follow-up time |
| Eder, 2016, Czech Republic[42] | RS | 26 adults, responsive to induction doses of anti-TNF, median age (IQR) 27 yr (IQR: 21-36), 61% F, L3, B1 62%, B2 7%, B3 31% | Median (IQR): 4 (2-6) | Study MD: IFX or ADA, 1 yr Concomitant MD: CS 88%, AZA 88%, 5ASA 100%, AB 54% | Predictive role of MH, TH and IH healing on long-term CR | Clinical, endoscopic, and MRE activity: before starting anti-TNF and after induction (week 12-14 for ADA and week 9-12 for IFX) | Median 29 mo (IQR: 14-46) after finishing 1 yr of anti-TNF |
| Sauer, 2016, United States[43] | RS | 101 children, 41.6% F, L1 28%, L2 24%, L3 54.5%, L4a 17.8%, L4b 24.7%, B1 76%, B2 18%, B3 2%, B2B3 4%, perianal 14% | Median (range): 4.7 (1.65-11.5) | IMD 33%, Biologic 67% | Predictive role of MRE remission on long-term CR, MD change and surgery | MRE, at median of 1.3 yr from diagnosis | Median 2.8 yr after MRE |
| Deepak, 2016, United States[14] | RS | 150 adults, 66% treatment-naïve, median age (IQR) at diagnosis 23 yr (IQR: 19-33), 50% F, L1 48.7%, L3 40.7%, L4 10.6%, B1 45%, B2 35.3%, B3 19.3%, perianal 19.3%, prior CD-related surgery 61.3% | Median (IQR): 9 (3-21) | At second CTE/MRE: Anti-TNF alone: 20%, THIO alone 36%, MTX alone 5.3%, Anti-TNF + THIO 24%, Anti-TNF + MTX 5.3%, Budesonide 8%, Natalizumab 1.4% | Predictive role of radiologic response on long-term outcomes: CS use, hospitalization, and surgery | Serial CTE/MRE: first and follow-up (705 CTE/MREs): pre-therapy and after 6 mo or 2 CTE/MREs ≥ 6 mo apart (during maintenance therapy) | Median 4.6 yr (IQR: 1.6-7) |
| Fernandes, 2017, Spain[13] | RS | 214 adults, 49.5% F, median age (IQR) 36.8 (16–77) yr, L1 76.6%, L3 23.4%, L4 10.3%, B1 44.4%, B2 26.2%, B3 29.4%, perianal 29.9%, prior intestinal resection 40.7% | Median (IQR): 7.4 (0-40.8) | THIO 54.7%, MTX 0.5%, Anti-TNF 18.7% | Predictive roles of MH and TH for hospital admission, surgery and MD escalation (start an IMD or biologic, escalate anti-TNF or switch to a different biologic) | MRE and IC performed within a 6-mo interval (median: 2.3 mo) | Median (IQR): 3.5 (1-7.9) yr Evaluation after 12 mo |
| Ripollés, 2016, Spain[41] | PS multicenter | 51 adults, active disease, 47% F, median age (IQR) 35 yr (27-46), L1 57%, L2 21.5%, L3 21.5%, B1 57%, B2 10%, B3 33%, perianal 27.5%, history of surgery 33% | Median (IQR): 5 (2-10.3) | Active MD: Anti -TNF (IFX or ADA) 100% (63% combined with IMD) | Predictive role of TH on clinical outcome, change in MD, surgery | Clinical and US / CEUS at baseline, 12 wk and 1 yr after treatment | Median (IQR): 16 mo (12.2-32) |
| Orlando, 2018, Italy[44] | PS | 30 adults, 33.3% F, mean age (± SD) 38.8 (± 14.5) yr, L1 40%, L3 60%, B1 53.3%, B2 40%, B3 6.7%, prior intestinal resection 40% | Mean ± SD: 9.8 ± 7.7 | Active MD: Anti-TNF (IFX 53.3%, ADA 46.7%) Concomitant MD: 5ASA 10%, CS 10%, THIO 16.7% | Predictive role of TH and intestinal fibrosis on clinical outcome (hospitalization and surgery) | US and UEI at baseline, 14 and 52 wk after therapy | Median (range): 20 mo (10-38) |
| Laterza, 2018, Italy[15] | PS | 57 adults, mean age (± SD) 45.3 (± 17) yr, 42.2% F, L1 38.6%, L2 8.7%, L3 52.6%, B1 31.6%, B2 54.4%, B3 14%, perianal 7%, previous surgery 22.8% | Mean ± SD: 7.4 ± 1 | No therapy 10.5%, CS 26.3%, Anti-TNF 10.5%, CS + IMD 15.8%, CS + anti-TNF 8.8%, IMD + anti-TNF 8.8%, CS + IMD + anti-TNF 19.2% | Predictive role of a single and/or combined (CR, MH and TH) remission on outcomes (surgery, hospitalizations, MD changes - introduction of IMD or anti-TNF, anti-TNF escalation, switch to another anti-TNF, need for CS and deaths) | Clinical, endoscopic and CTE at baseline | Up to 36 mo |
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 |
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 |
- Citation: Serban ED. Treat-to-target in Crohn’s disease: Will transmural healing become a therapeutic endpoint? World J Clin Cases 2018; 6(12): 501-513
- URL: https://www.wjgnet.com/2307-8960/full/v6/i12/501.htm
- DOI: https://dx.doi.org/10.12998/wjcc.v6.i12.501