Table 1.

Crohn’s disease—full-text articles—adults.

Author	No. of patients	Treatment	Time point of assessment	Reference standard	IUS response/remission definition	BWT decrease or no. of patients with/without increased BWT	CDS decrease or no. of patients with/without increased CDS	IUS remission	IUS response/remission association with reference standard
Paredes 201916	33	Anti-TNF	Baseline, 12 weeks, 1 year	CDAI	Response: decrease in BWT >2 mm and CDS decrease by 1 grade. Remission: BWT ≤3 mm and CDS grade 0 or 1	Week 12: Median decrease 1.5 mm [24%]	Baseline: CDS 2 or 3: 28 [85%] Week 12: 11 [33%], p <0001	Week 12: 7 [21%]. 1 year: 14 [42%]	N/A
Paredes 201017	24	Anti-TNF	Baseline, 2 weeks after induction	CDAI	Response: BWT decrease >0.5 mm and CDS decrease by 1 grade. Remission: BWT ≤3 mm, CDS grade 0, no intraabdominal complications	Decrease in 11 [46%] patients. Responders [mean ± SD]: 1.2 ± 1.6 mm [19%]. Non-responders: 0.1 ± 0.2 mm, p = 0.01	Baseline: CDS 2 or 3: 17 [71%] 2 weeks after induction: 11 [46%] p <0.02.CDS decreased in 10 [42%]	BWT normalisation: 29%. CDS normalisation: 33%. Transmural complications: 50%	No decrease of BWT or CDS in patients without treatment response, p <0.05
Castiglione 201318	133	Anti-TNF or AZA/6-MP	Baseline, 2 years	CDAI, SES-CD, CRP	Response: N/A. Remission: BWT <3 mm	Mean decrease anti-TNF: 2.0 mm [33%], AZA/6-MP: 0.4 mm [6%]	N/A	Anti-TNF: 17/66 [25%] .AZA/6-MP: 3/67 [5%]	TR with ER: κ = 063, p = 001. 2 TR cases were without ER. TR with CDAI: κ = 027, p <0.01. TR with CRP: κ=079, p = 0.02
Castiglione 201719	40	Anti-TNF	Baseline, 2 years	CDAI, SES-CD, MRE	Response: N/A. Remission: BWT ≤3 mm	Mean decrease IUS: 2.2 mm [36%]. MRE: 2.7 mm [N/A]	N/A	10 [25%]: Type of anti-TNF did not determine a significant difference in TR outcome	IUS remission and ER κ = 063, p <0.01. IUS remission and MRE remission κ = 090; p <0.01. CRP and TR κ = 027, p = <0.01. TR and CRP κ = 079, p = 0.02
Kucharzik 201720	234	CS, anti-TNF, AZA/MTX, 5-ASA	Baseline, 3 months, 6 months, and 12 months	HBI	Abnormal BWT TI: >2 mm. Colon: >3 mm.Response: N/A.Remission: N/A	Sub-group 1 [all scans, N = 134]: abnormal BWT at baseline, 3, 6, and 12 months: TI: 75%, 57%, 44% ,and 36%. Sigmoid: 47%, 22%, 27%, 23% .All with p-values <0.05. Sub-group 2 [baseline, 3 months, N = 182] TI normalisation: 107 [59%]. A 10% or 25% BWT reduction was found in 95% and 80% of patients, respectively	Sub-group 1: CDS 3 + 4. Baseline, 3, 6, and 12 months: 44%, 18%, 14%, and 10%, p <0.001	N/A	Sub-group 2: BWT reduction = HBI reduction in 86%. CDS change [3 + 4  =  >1 + 2] correlated with CRP at Months 3 and 12 in both sub-groups. Sub-group 2: correlation between CRP and BWT [TI], Spearman = 0.46 and BWT and HBI [transverse colon], Spearman 0.42
Ripolles 201621	51	Anti-TNF. Anti-TNF + AZA/MTX	Baseline, 12 weeks, 1 year,2 years [clinical]	HBI, CRP	Response: decrease in BWT [≥2 mm], CDS [≥1], CEUS—mural enhancement [≥20%] and/or absence of complications. Remission: BWT ≤3 mm, CDS = 0, no complications	12 weeks mean decrease: 1.2 mm [18%], p <0.05. 52 weeks: 1.5 mm [24%], p = NS	Baseline CDS 3–4: 43 [84%]. 12 weeks: 19 [37%] p = 0.0001. 52 weeks: 19 [37%] p = NS.26 [51%] improved with normalisation in 7	N/A	N/A
Ripolles 200822	28	5-ASA or CS ± AZA	Baseline, 3–8 days, 4 weeks	CDAI, CRP	BWT >= 3 mm abnormal. Response: decrease in CDS [3 = >2 or 2 = >0/1, not from 1 = >0] and BWT [≥25% decrease]. Sonographic active disease: CDS ≥2 or BWT >5 mm	4 weeks mean decrease 0.8 mm [12%], p = NS	Baseline: grade 2–3 vascularity: 18/22 [82%]. CDAI >150 and 4/6 [67%]. CDAI <150 2nd examination: improvement	N/A	No correlation between clinical and sonographic changes between baseline, 2nd and 3rd examination
							in 5/22 [23%]. 3rd examination: 15/22 [68%] with increased vascularity
Dubbins 198423	19	AZA/MTX	Baseline, 2–4 months	N/A	N/A	Mean decrease 6 mm [60%]	N/A	N/A	N/A
Onali 201024	25	5-ASA ± CS	1 year, 2 years, 3 years	CDAI, Rutgeerts’ score, SBFT	CD recurrence: 1 ]BWT >3 mm. 2] stiff loop = increased BWT, not distended by oral contrast. 3] small bowel dilation, diameter >2.5 cm	1-year recurrence: 25/25 [100%]. BWT median [range] 5 mm [35–10]. 3.5 mm in one patient with Rutgeerts’ i0. 2 years: 21/21 [100%]. 3 years: 15/15 [100%]. 3.5 mm in one patient with Rutgeerts’ i0	N/A	N/A	N/A
Moreno 201425	30	Anti-TNF ± AZA/6-MP	Baseline, 14 months [range: 13–25 months]	CDEIS	Remission: BWT ≤3 mm, CDS = 0–1, and CEUS peak enhancement <46%	Mean decrease 3 mm [40%], p = <0.05	Baseline CDS 3–4: 27 [90%]. After treatment: 6 [20%], p ≤0.001	Segmental assessment: 37/59 [64%]. Overall assessment: 15/30 [50%]	Segmental: association: TR vs. ER: [κ = 0.76; p <0.001]. BWT ≤3 mm predicts ER [93%]. Overall: TR vs. ER: [κ = 0.73, p <0.001] BWT ≤3 mm predicts ER [96%]
Orlando 201826	30	Anti-TNF	Baseline, 14 weeks, 52 weeks	Surgery is outcome	Remission: BWT ≤3 mm	Mean SD decrease 0.74 ± 1.2 mm [1.25 ± 1.95%], p ≤0.05. ADA vs. IFX = NS	BWT variations and TR were not influenced by CDS or BWS [p = NS]	Week 14: 8 [27%]. Week 52: 9 [30%]	N/A
Socaciu 201527Δ	13	N/A	Baseline, 12 weeks	CDAI	N/A	12 weeks decrease: 1.7 mm [25%]	N/A	N/A	Wilcoxon [z = 213, p = 0.033]. Spearman: [rho = 065, p = 0.015]
Goertz 201828Δ	11	VED	Baseline,2 weeks, 6 weeks, 14 weeks	HBI	N/A	5 responders: baseline: 5.3 ± 0.8 mm. Week 14: 5.3 ± 1.8 mm. 6 non-responders: baseline: 6.6 ± 0.6 mm. 14 weeks 6.1 ± 1.2mm	5 responders: baseline: 2.4 ± 0.9. Week 1.4: 1.2 ± 0.8. 6 non-responders: baseline: 2.0 ± 0.6, 14 weeks 1.5 ± 0.8	N/A	N/A
Quaia 201929	115	Anti-TNF ± CS	Baseline, 6 to 18 weeks	CDAI, CDEIS	N/A	12 weeks decrease: response group: 3.0 mm [43%]. Non-response group: 1.0 mm [14%]	N/A	N/A	N/A
Saevik 201430	14	CS or anti-TNF	Baseline, 1 month, 3 months, 12 months	CDAI	BWT > 2 mm abnormal if lumen >0.5 cm or abnormal if BWT > 3 mm + lumen <0.5 cm	1-month decrease: 0.3 mm [5%]. 12 weeks: 0.01 mm [0.2%]. 1 year: 1.6 mm [34%]	N/A	N/A	N/A
Chen 201831	29	AZA + EEN	Baseline and when clinical parameters became normal	CDAI, SES-CD	Remission: ≤3 mm and normalisation of IUS parameters.b CDS 3/4: positive	Decrease 4.4 mm [47%], p <0.05	Positive baseline: 90%.During follow-up: 17%, p <0..05	5 [17%]	N/A
Hoffman 201932	57	UST	Baseline,24 ± 6 weeks,24–48 ± 6 weeks	HBI	Response: ≤3 mm	Baseline abnormal BWT: 19/22 [79%]. 24 ± 6 weeks, 8/13 steroid free clinical remission/response vs. 5/13 non-response. 6/13 [46%] had BWT >3 mm, p = 0.43. Weeks 24–48 ± 6: 6/13 in response /remission with improvement or no inflammation vs. 5/13 non-response, p = NS	N/A	N/A	N/A
Zorzi 201933	80	Anti-TNF	Baseline, 18 months [median]	ER	BWT: >3 mm, abnormal. Improved lesions: [a] BWT improvement [≥1 mm] or normalisation TI <3 mm; colon <4 mm; [b] decreased length; [c] no worsening of other IUS parametersc	41 [51%] were classified as responders, 27 [34%] as partial responders, and 12 [15%] as non-responders. There was a significant relationship between ultrasonographic response and clinical outcomes considered	N/A	N/A	N/A
Calabrese 202134	188	ADA, IFX, UST, VED	Baseline,3 months,6 months,12 months	HBI, CRP, FCP	Remission: ileum BWT ≤ 3 mm, colon BWT ≤4 mm and normalisation of other parametersd	Ileum: median decrease 3 months: 0.5 mm [8%]. 6 months: 1 mm [17%]. 12 months: 1 mm [17%], p <0.05. Colon: 3 months: 0.85 mm [14%]. 6 months: 1.45 mm [23%]. 12 months: 2.35 mm [37%], p <0.05	Ileum: baseline: 125/158 [79%] with increased CDS. 3 months: 89/158 [56%]. 6 months: 67/156 [43%]. 12 months: 52/133 [39%], p <0.05. Colon: baseline: 22/30 [73%].	3 months: 31/188 [16%]. 6 months: 42/171 [25%]. 12 months: 43/156 [28%] [ADA 27%, IFX 37%, VED 27%, UST 20%]	N/A
							3 months: 14/30 [47%]. 6 months: 10/25 [40%]. 12 months: 9/23 [39%], p <0.05
Hoffman 202035	23	UST	Baseline,8 weeks	CDAI, CRP	Response: decrease of BWT ≥1.0 mm	10/23 [43%] responded	Baseline: 9 patients with Limberg 2. 8 weeks: 4	N/A	Responders: substantial decrease in CDAI ≥70 points and CRP ≥0.5 mg/dl in 9/10 and 8/10, respectively
Li Ma 202136	77	AZA/MTX ± Anti-TNF, 5-ASA	Baseline,6 months	CDAI, CRP, SES-CD, CTE, MRE	Remission: BWT ≤ 3 mm and normalisation of other parameterse	N/A	N/A	6 months: 25/77 [32%]	TR and ER poorly correlated, k = 0387, p < 005 TR and CTE highly correlated, k = 0793, p < 005
Helwig 202137f	180	AZA/MTX ± anti-TNF, anti-integrin, systemic CS	Baseline,12 ± 4 weeks,52 ± 4 weeks	HBI	Response: BWT reduction >25% or a normalisation of BWT.Remission: three different definitions. 1] Normalisation of BWT [Ileum ≤2 mm, sigmoid ≤4 mm, rest of colon ≤3 mm] and normalised CDS. 2] normalised BWT and CDS, restored BWS and no I-fat [minus one factor that could not be assessed]. 3] All factors normalised	12 weeks: No. of patients with response: 77/118 [65%]	N/A	12 weeks: Definition: 1: 58/180 [32%]2 67/180 [37%]3 43/180 [24%]	N/A
Jessen 202038g	21 CD, 20 UC	IFX	Baseline, Week 6	HBI, partial Mayo score	N/A	N/A	Data not stratified by disease. Responders: median 1 CDS point decreaseNon-responders: median 0 CDS points decrease	N/A	N/A

5-ASA, mesalazine; ADA, adalimumab; anti-TNF, infliximab and adalimumab; AZA, azathioprine; AZA/6-MP, azathioprine/mercaptopurine; AZA/MTX, azathioprine/methotrexate; BWS, bowel wall stratification; BWT, bowel wall thickness; CD, Crohn’s disease; CDAI,Crohn’s Disease Activity Index; CDS, colour Doppler signal; CRP, C-reactive protein; CS, corticosteroids; CTE, computer tomography enterography; EEN, Total Protein Enteral Nutritional Powder; ER, endoscopic remission; FCP, faecal calprotectin; HBI, Harvey-Bradshaw Index; IFX, infliximab; IUS, intestinal ultrasound; MRE, magnetic resonance enterography; N/A,not available; NS, not significant; UST, ustekinumab; SBFT, small bowel follow-through; SD, standard deviation; SES-CD,Simple Endoscopic Score—Crohn’s Disease; TI, terminal ileum; TR, transmural remission; UC, ulcerative colitis; VED, vedolizumab; CEUS, conteast-enhanced ultrasound.

^aNo colour Doppler signal, normal five-layer bowel wall stratification, no inflammatory fat, no lymph node enlargement, or presence of strictures or pre-stenotic dilation.

^bNo colour Doppler signal, normal bowel wall stratification, no pre-stenotic dilations, strictures, fistulae, inflammatory fat, abscesses, lymphadenopathy, or ascites.

^cOr fistulising disease.

^dColour Doppler signals, length of disease, bowel wall stratification, inflammatory mesenteric fat, lymph nodes, stenosis, pre-stenotic dilation, abscess, fissures, and fistulae

^eColour Doppler signals, bowel wall stratification, inflammatory mesenteric fat, abscesses, and fistulas=e.

^fReport data on both Crohn’s disease and ulcerative colitis, stratified by disease.

^gReport data on both Crohn’s disease and ulcerative colitis, not stratified by disease.