Intestinal ultrasound measurement of bowel wall thickness can be used as a sole marker for defining anti-TNF maintenance therapy failure in Crohn’s disease

Abstract

Introduction:

Bowel wall thickness (BWT) measurements in intestinal ultrasound (IUS) are recognized indicators of inflammatory activity in Crohn’s disease (CD). However, the added value of other ultrasonographic parameters for monitoring and predicting treatment failure during anti-tumor necrosis factors’ (TNF) maintenance therapy is still not absolutely defined.

Objectives:

To determine whether BWT, as measured by IUS, can serve as a reliable single marker for predicting treatment failure in CD patients under anti-TNF therapy, compared to a combination of ultrasonographic parameters.

Design:

This study was a single-center, retrospective cohort study.

Methods:

This study included 103 CD patients in clinical remission on anti-TNF therapy, who had an IUS examination within 10 months following therapy initiation. We investigated the correlation of these ultrasonographic parameters with subsequent treatment failures, defined by disease flares, and the need for surgery, hospitalization, corticosteroid use, dose escalation, and drug discontinuation.

Results:

Treatment failure occurred in 59.2% of patients within a median of 5 months post-index IUS. Significant differences were observed in BWT (3.9 mm in the failure group vs 3 mm in the remission group, p = 0.007), bowel wall flow (BWF; 49.2% vs 23.8%, p = 0.009), and mesenteric hypertrophy (20.4% vs 7.1%, p = 0.006). In receiver operating characteristic analysis for BWT, the area under the curve (AUC) of BWT >3 mm was 0.66, with a sensitivity of 67.2% and specificity of 69.1%. The combined (BWT, BWF, and mesenteric hypertrophy) AUC was 0.68 (sensitivity of 62.9%, specificity of 61.9%). Delong’s test showed no significant difference in AUC (p = 0.137). BWT emerged as the most significant parameter in stepwise regression analysis.

Conclusion:

Our findings suggest that BWT alone may be used as a single ultrasonographic marker of treatment, therefore simplifying the use of IUS. Using a single objective ultrasonographic parameter simplifies the use of IUS, an important factor that can facilitate the use of this important imaging technique.

Graphical abstract

Plain language summary

Using bowel thickness alone to predict treatment failure in Crohn’s disease

This study explored whether bowel wall thickness (BWT) measured by intestinal ultrasound (IUS) could predict treatment failure in Crohn’s disease (CD) patients receiving anti-TNF therapy. Among 103 patients, BWT greater than 3 mm was strongly associated with treatment failure, including disease flares, surgery, and medication changes. Using BWT alone was as effective as combining it with other parameters, like bowel wall flow and mesenteric hypertrophy. This simplified approach reduces exam time, improves accessibility, and supports IUS as a quick, non-invasive tool for monitoring CD. The findings highlight BWT’s potential to guide early intervention and improve treatment outcomes for patients.

Keywords

anti-TNF therapy bowel wall thickness (BWT)intestinal ultrasound (IUS)therapy failure

Introduction

Crohn’s disease (CD) is a chronic, transmural, relapsing disease that may cause significant complications, leading to recurrent hospitalization and surgery.^1,2 The medical management of CD aims to induce and maintain remission and to prevent complications.^3,4 A considerable proportion of patients experience treatment failure or intolerance, necessitating therapy escalation or a switch to alternative therapies.⁵

Intestinal ultrasound (IUS) is used as an objective and effective tool for the diagnosis and monitoring of CD, which enables the identification of early failure to treatment and prediction of disease exacerbations as well as postoperative recurrence.^6
–13

Bowel wall thickness (BWT) is a key ultrasonographic marker of inflammatory activity in CD, correlating with disease severity and predicting treatment response. Changes in BWT during treatment offer crucial insights into the effectiveness of therapies, enabling adjustments to treatment plans and reflecting transmural healing (TMH), underscoring its potential as a noninvasive marker for comprehensive disease management.^14,15 Other signs include excessive blood flow (bowel wall flow, BWF) within the affected bowel segment, loss of bowel wall stratification (BWS), mesenteric fat hypertrophy, enlarged lymph nodes, stricture, and the presence of extraintestinal complications, such as abscesses or fistulae.^9,16,17

Although the significance of BWT has been extensively examined, less is known about the use of BWT as a standalone predictor with comprehensive IUS measurements. In addition, the added value of other IUS activity parameters is not thoroughly defined. Therefore, we aimed to test whether the sole use of BWT is sufficient for the characterization of treatment failure and to examine the added value of the other ultrasonographic activity signs to that of BWT during biological maintenance therapy in CD patients and their proficiency to detect treatment failure.

Materials and methods

Study population and design

We conducted a retrospective, single-center cohort study at Sheba Medical Center. The study population included adult CD patients treated with scheduled maintenance anti-tumor necrosis factor (TNF) therapy (infliximab (IFX) or adalimumab (ADA)), who had undergone at least one IUS exam 6–18 months after therapy initiation and were in clinical remission (Harvey-Bradshaw index ⩽4) at the time of the IUS. Patients, from July 2017 to July 2022, were selected consecutively from the medical records of all patients meeting the inclusion criteria, and the following variables were collected for each patient: age, gender, disease duration, disease location, disease behavior as per the Montreal classification, perianal involvement, smoking status, extraintestinal manifestations (EIMs), and previous surgeries. In addition, information regarding drug therapies, including the type, dosage, and duration of treatment, was also recorded.

We excluded patients <18 years, pregnant women, unconfirmed CD diagnosis at the time of data collection, and cases with the absence of a formal IUS report.

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Sheba Medical Center ethics committee (Approval Number: SMC-5598-08), and patient consent was waived. The reporting of this study confirms the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.¹⁸

Intestinal ultrasound

The IUS scans were performed by two experienced sonographers (D.C., A.A.). The IUS exams were performed using a GE Logiq S8 ultrasound machine with convex (3.5–5 MHz) and linear probes (7.5–10 MHz). All examinations were performed without any preceding preparation, using a consistent technique and protocol, beginning the examination with the terminal ileum (TI), proximal to distal colon, followed by a scan of the small bowel. The bowel activity parameters assessed included BWT, which was measured in longitudinal sections in at least two different areas at a minimal distance of 1 cm from each other. The thickest segment of each bowel part was recorded. Additional signs of inflammation were documented, including Doppler signals for BWF using the modified Limberg scoring system (0 = absent signal; 1 = short signals inside the bowel; 2 = long signals inside the bowel; 3 = long signals inside and outside of the bowel—for statistics we include 1–3 as abnormal bowel flow), the presence (or absence) of mesenteric fat hypertrophy, BWS and lymph node enlargement, intramural and extramural complications, such as strictures with or without pre-stenotic dilatations, fistulas, and abscesses, were also recorded. A formal standardized protocol for IUS reporting was documented.

Outcome and definitions

The primary outcome of this study was to assess whether BWT measurements can be solely used (without the need for assessment of other parameters) for the detection of treatment failure and to examine the added value of various ultrasonographic activity signs, alongside BWT, and their association with subsequent treatment failure. Treatment failure was defined as disease flare and the necessity for CD-related surgery, hospitalization, corticosteroid usage, dosage adjustments (including dose escalation or shortening of administration periods), and drug discontinuation. A disease flare was defined as a clinical exacerbation combined with elevated inflammatory parameters and/or active disease evident in endoscopy or imaging. The first occurrence was calculated as the primary cause of failure. All examinations were performed as part of the routine clinical practice, and the performers were blinded to the patients’ outcomes. The therapeutic adjustments post-IUS were not solely based on ultrasonographic findings; they were made after a thorough clinical evaluation by the treating physician. The outcome data were collected separately for this study.

Statistical analysis

We used descriptive statistics to examine the socio-demographic and clinical characteristics of the study cohort. We presented each variable with the most suitable central and dispersion measures. Dichotomous and nominal variables (e.g., sex, phenotype) were presented by number and %. Numerical (continuous) variables (e.g., patient age) were described by mean ± standard deviation (SD). Numerical (count) variables (e.g., EIM) were presented by median and interquartile range (IQR).

First, we used univariate analysis to examine the association between sociodemographic and clinical characteristics with treatment failure and discontinuation of medication. For nominal variables, we used either the Chi-square or Fisher’s exact test. For continuous variables with a normal distribution, we used an independent T-test. For continuous variables with non-normal distribution or count variables, we used Mann–Whitney test. The normality of continuous variables was assessed using Q–Q plots, the Shapiro–Wilk test, and the Kolmogorov–Smirnov test.

Next, we used multivariable logistic regression to examine the association between clinical characteristics and treatment failure and discontinuation of medication after adjusting for potential confounders, which showed a significant association with the dependent variable. Also, the stepwise backward selection method was used to select the most significant predictors out of the variables that showed a significant association in the multivariable regression. Finally, receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of two regression models: (1) BWT alone adjusted to potential confounders from the original multivariable model compared to (2) a combined model incorporating BWT, BWF, and mesenteric hypertrophy. Also, we used DeLong’s test to compare the models.

In addition, we analyzed the correlation between BWT and other parameters. Pearson or Spearman correlation coefficients were used based on the distribution of the data to assess the strength and direction of these relationships.

All analyses were conducted using SPSS Statistics V. 25 and R software. A two-sided test significance level of 0.05 was used throughout the entire study.

Results

A total of 103 consecutive CD patients (54.4% male and 45.6% female) who initiated anti-TNF therapy between July 2017 and July 2022 were included (67% ADA and 33% IFX; Figure 1). The median disease duration was 6 years (IQR 4–13). Most patients had ileal involvement (n = 59.2%), followed by ileocolic (n = 35.9%) and colonic involvement (n = 4.9%). The clinical and demographic characteristics of the included patients are detailed in Table 1. IUS was performed within a median of 10 months (6–18) of anti-TNF therapy initiation. All patients were in clinical remission during the time of the ultrasonographic assessment.

Figure 1.

Flowchart presenting the selection process and outcomes.

Table 1.

Baseline characteristics of the CD patients included in the study.

Variable	All patients (n = 103)
Patient sex
Male	56(54.4)
Female	47(45.6)
Age at diagnosis, years	26.1 ± 9.9
Disease duration, years	6(4–13)
HBI ( at the time of IUS)	3(2–4)
Smoking
No	73(70.9)
Active	17(16.5)
Previous	13(12.6)
Disease location
L1	61(59.2)
L2	5(4.9)
L3	37(35.9)
Disease phenotype
B1	44(42.7)
B2	28(27.2)
B3	31(30.1)
Perianal disease	16(15.5)
Previous surgeries	34(33.0)
EIM	0(0–1)
Anti-TNF therapy
IFX	34(33.0)
ADA	69(67.0)
Time anti-TNF to IUS, months	10.6 ± 3.3

No. (%); mean ± SD; median(IQR).

ADA, adalimumab; anti-TNF, anti-tumor necrosis factor; B1, non-stricturing non-penetrating; B2, stricturing; B3, penetrating; EIM, extraintestinal manifestations; HBI, Harvey–Bradshaw index; IFX, infliximab; IQR, interquartile range; IUS, intestinal ultrasound; L1, small bowel disease; L2, colonic disease; L3, ileocolonic; SD, standard deviation.

The median duration of follow-up after the index IUS examination was 15 months (5–35). Sixty-one out of the 103 patients (59.2%) experienced treatment failure that occurred at a median of 5 months (2–12.5) following the performance of the IUS exam. Twenty-three (37.7%) patients required an increase in the anti-TNF dosage, 22 (36%) required a switch to other biological medication, 6 (9.9%) required corticosteroid use, 5 (8.2%) underwent CD-related surgery (4 for luminal disease and 1 for perianal disease), and 5 (8.2%) required hospitalization. There was no significant difference between the groups in terms of disease duration, type of anti-TNF treatment, treatment duration, smoking status, or disease location. The only significant distinction was in EIMs, which were more pronounced in the treatment-failing group (Supplemental Table 1).

Pathological IUS findings were significantly more common in the treatment failure group (Supplemental Table 2). These parameters include thickened BWT (median 3.9 mm (IQR 2–5.2 mm) vs 3 mm (2–3.5 mm), p = 0.007), increased BWF (49.2% vs 23.8%, p = 0.009), mesenteric hypertrophy (29.5% vs 7.1%, p = 0.006), BWS (16.4% vs 0%, p = 0.005), and complications (abscess, fistula, stricture; 14.8% vs 2.4%, p = 0.045).

On multivariate analysis, BWT >3 mm (odds ratio (OR): 3.25, 95% confidence interval (CI): 1.30–8.12, p = 0.012), abnormal BWF (OR: 2.93, 95% CI: 1.16–7.39, p = 0.023), and mesenteric hypertrophy (OR: 4.44, 95% CI: 1.15–17.07, p = 0.030) were independently associated with therapy failure (Table 2). The ROC curve illustrating the correlation with treatment failure using various BWT thresholds is presented in Figure 2. The diagnostic performance of these individual IUS parameters and their combined model is summarized in Table 3, highlighting their predictive value for the detection of therapy failure.

Table 2.

Multivariable logistic regression of sonographic characteristics associated with treatment failure.

Variable	aOR	95% CI	p-Value
MAX BWT	1.42	1.04–1.93	0.027
MAX BWT
⩾3	3.25	1.30–8.12	0.012
⩾3.5	2.70	1.07–6.78	0.035
⩾4	2.47	0.93–6.51	0.068
⩾4.5	2.45	0.85–7.09	0.099
⩾5	3.02	0.88–10.30	0.078
⩾5.5	1.96	0.47–8.10	0.354
BWF high	2.93	1.16–7.39	0.023
Enlarged lymph nodes	1.41	0.32–6.34	0.651
Fat hypertrophy	4.44	1.15–17.07	0.030
Disturbed BWS	4.64	0.93–23.20	0.062
IUS complication	6.04	0.69–52.59	0.104

Bolded values indicate statistically significant associations (p < 0.05).

aOR, adjusted odds ratio; BWF, bowel wall flow; BWS, bowel wall stratifications; BWT, bowel wall thickness; CI, confidence interval; IUS, intestinal ultrasound; MAX BWT, maximal bowel wall thickness.

Figure 2.

ROC curve analysis for correlating outcomes. (a) Displays ROC curves assessing the sensitivity and specificity of multiple Max-BWT thresholds for correlating with treatment failure. Each line represents a different threshold from ⩾3 to ⩾5.5 mm. The blue line (Max BWT ⩾3 mm): This specific threshold shows an AUC of 0.66, with a sensitivity of 57.4% and specificity of 73.8%, highlighting its utility in identifying patients at risk of therapy failure. It also shows an NPV of 54.4% and a PPV of 76.1%. (b) For different Max BWT thresholds correlating with drug discontinuation. The green line represents the ROC curve for BWT ⩾4 mm, with an AUC of 0.65, showcasing a sensitivity of 50.0% and specificity of 80.7%. The NPV of 66.7% and the PPV of 67.7%. (c) ROC curves for two regression models correlating with the presence of therapy failure. The red curve represents the model using BWT alone, which achieved an AUC of 0.74 (95% CI: 0.64–0.84). The blue curve represents the model using BWT, BWF, and mesenteric hypertrophy, with an AUC of 0.67 (95% CI: 0.56–0.77). DeLong’s test confirms that there is no statistically significant difference between the models (p-value = 0.137).

Table 3.

The diagnostic performance of individual IUS parameters and their combined model.

Variable	Sensitivity (%)	Specificity (%)	NPV (%)	PPV (%)	AUC
BWT	67.2	69.1	59.2	75.9	0.66
BWF	49.2	76.2	50.8	75.0	0.63
Fat hypertrophy	29.5	92.9	47.6	85.7	0.61
Combined model	75.4	61.9	36.6	74.2	0.68

AUC, area under the curve; BWF, bowel wall flow; BWT, bowel wall thickness; IUS, intestinal ultrasound; NPV, negative predictive value; PPV, positive predictive value.

A subgroup analysis focusing on the group that discontinued anti-TNF treatment was performed. This analysis included all instances of treatment failure, not just the first cause. Overall, an additional 24 patients discontinued therapy. In 12 patients, previous dose escalation failed to achieve a treatment response, in 9 patients, treatment was discontinued due to hospitalization or steroid dependency, and 3 patients required surgical interventions.

Therefore, drug discontinuation occurred in 46 (44.6%) patients with a median time of 19 months (6.7–35) following the IUS examination. This cohort compared to therapy failure group without drug discontinuation was found to have significantly longer disease duration (10.8 ± 9.3 vs 8.1 ± 9, p = 0.036), an older age at the diagnosis (28.9 ± 10.5 vs 23.8 ± 8.8, p = 0.012), and diagnosis of EIMs (p = 0.02).

BWT of ⩾4 mm was significantly associated with drug discontinuation (Figure 2). The association of the other IUS inflammatory parameters with treatment failure is described in Table 4. On multivariate analysis, only increased BWT (⩾4 mm; OR: 2.68, 95% CI: 1.04–6.89, p = 0.042) and mesenteric hypertrophy (OR: 5.29, 95% CI: 1.61–17.44, p = 0.006) were significantly associated with drug discontinuation (Supplemental Table 3).

Table 4.

Univariate analysis results of sonographic characteristics associated with discontinuation of anti-TNF therapy.

Variable	Stopped (n = 46)	Continued (N = 57)	All patients (n = 103)	p-Value
MAX BWT	4.0 ± 1.7	3.2 ± 1.5	3.5 ± 1.6	0.013 ^a
MAX BWT
⩾3	28(60.9)	18(31.6)	46(44.7)	0.003 ^b
⩾3.5	24(52.2)	16(28.1)	40(38.8)	0.013 ^b
⩾4	23(50.0)	11(19.3)	34(33.0)	0.001 ^b
⩾4.5	18(39.1)	9(15.8)	27(26.2)	0.007 ^b
⩾5	14(30.4)	7(12.3)	21(20.4)	0.023 ^b
⩾5.5	9(19.6)	5(8.8)	14(13.6)	0.112^b
BWF high	22(47.8)	18)31.6)	40(38.8)	0.093 ^b
Enlarged lymph nodes	4(8.7)	5(8.8)	9(8.7)	1.00^b
Fat hypertrophy	16(34.8)	5(8.8)	21(20.4)	0.001 ^b
Disturbed BWS	8(17.4)	2(3.5)	10(9.7)	0.040 ^c
IUS complication	8(17.4)	2(3.5)	10(9.7)	0.040 ^c

Boldface type indicates p < 0.05. No. (%); mean ± SD; median (IQR).

Mann–Whitney.

Chi-square.

Fisher.

Bolded values indicate statistically significant associations (p < 0.05); Anti-TNF, anti-tumor necrosis factor; BWF, bowel wall flow; BWS, bowel wall stratifications; BWT, bowel wall thickness; IUS, intestinal ultrasound; MAX BWT, maximal bowel wall thickness.

There was a significant correlation between BWT and BWF (r = 0.56, p < 0.001) and between BWT and fat hypertrophy (r = 0.50, p < 0.001). In a stepwise regression model, BWT was the only significant parameter associated with therapy failure, with a coefficient (B) of 0.432 (p = 0.005). In the sub-analysis for the drug discontinuation subgroup with a BWT ⩾4 mm, the coefficient (B) was 1.431 (p = 0.001). BWF and fat hypertrophy were not included in the model due to their lack of statistical significance. The ROC curves demonstrated that the adjusted BWT model achieved a higher area under the curve (AUC: 0.74, 95% CI: 0.64–0.84) compared to the combined model (BWT, BWF, and fat hypertrophy; AUC = 0.67, 95% CI: 0.56–0.77). However, DeLong’s test showed no significant difference in AUC between the two models (p = 0.137; Figure 2). This finding, together with the stepwise analysis results, suggests that BWT alone is the most effective marker of therapy failure.

Discussion

This study emphasizes the fundamental role of BWT as a key ultrasonographic marker that is associated with treatment failure in CD. This finding may simplify IUS performance, decrease examination time, assist external central reading of IUS for studies, and make artificial intelligence-assisted IUS analysis more achievable.

BWT serves as a surrogate of transmural response to treatment. Previous studies have demonstrated high sensitivity and specificity of BWT for the diagnosis and follow-up of IBD patients.^9,12,13,19 Moreover, BWT was previously demonstrated to have the potential to be used as a single ultrasonographic sign for the follow-up and prediction of therapeutic response in CD^12
–15,20 and to guide treatment decisions, such as the initiation of appropriate medications or adjustments in therapy to induce and maintain remission.²¹ Furthermore, previous studies had demonstrated the correlation between anti-TNF drug levels and BWT.^12,13,22

In this study, we decided not to include formal IUS activity scores, such as International Bowel Ultrasound Segmental Activity Score or Bowel ultrasound score (BUSS),^23,24 as our primary objective was to simplify IUS assessment by focusing on BWT as a single marker. BWT alone demonstrated significant correlation to treatment failure, and streamlining IUS reporting could enhance its accessibility in routine clinical practice. Future prospective studies could explore the additional utility of incorporating these activity scores in a more structured setting.

The use of TMH as a treatment goal is expanding rapidly. TMH is associated with improved long-term outcomes and a reduced risk of complications such as fistulas and surgery.^14,15

In this study, we have demonstrated a significant association between BWT >3 mm and treatment failure in patients receiving anti-TNF therapy during the maintenance phase and in clinical remission. Furthermore, BWT ⩾4 mm was significantly associated with drug discontinuation. In addition, in the stepwise and ROC analyses, BWT was the most significant IUS parameter related to therapy failure. Therefore, our study results also support the use of TMH assessment as a treatment target in CD.

BWF assesses the hyperemia of the bowel wall and is evaluated using color Doppler.²⁵ Increased vascular signal in the submucosa that penetrates the muscularis propria has been identified as a significant marker of inflammation in patients with CD, and a heightened signal is predictive of more severe disease.^26,27

We demonstrated that increased BWF is significantly associated with treatment failure, although its impact on drug discontinuations was less prominent. This finding can be attributed to the presence of fibrosis in the involved intestinal loops, translated into an IUS image of increased BWT without an increase in BWF.

The data on the prevalence and clinical impact of mesenteric fat hypertrophy on disease severity and management are limited. Mesenteric fat hypertrophy was previously reported to be correlated to biochemical and clinical activity of CD and to findings of increased BWT and extraintestinal complications.^28,29 In quiescent CD, mesenteric fat hypertrophy was not correlated with disease relapse.²⁸ In this study, mesenteric fat hypertrophy was significantly associated with therapy failure and drug discontinuation, highlighting the significance of this ultrasonic parameter of disease activity.

BWS represents the finding of partially or extensively disrupted bowel wall layering. The most common definition relates to a limited hypoechoic disruption or total loss of BWS.^30,31 In our cohort, the therapy failure group and drug discontinuation group had significantly higher rates of BWS loss in the univariate analysis. However, this effect was lost in the multivariate analysis.

Regional mesenteric lymphadenopathy detected by IUS is a common but nonspecific sonographic finding in CD and could be linked to young age, early disease, and the presence of extramural complications (abscesses or fistulae).³² However, the relation of this sign to disease behavior remains poorly investigated. In this study, we did not find a significant correlation between lymph node enlargement on IUS and therapy failure or drug discontinuation.

The significant correlation of BWT with BWF and fat hypertrophy highlights their interrelated roles in the ultrasonographic features of CD. However, BWT emerged as the most significant parameter in a stepwise regression analysis, demonstrating its robustness as a correlate of treatment failure. BWT alone is sufficient to define the risk of treatment failure, as BWF and fat hypertrophy were not included in the model due to their lack of statistical significance. This finding highlights BWT’s unique correlative power and supports its use as a singularly reliable marker in clinical practice for assessing and managing CD treatment outcomes.

Our study had several strengths, such as evaluating multiple parameters beyond the common inclusion of BWT and BWF. In addition, we assessed patients who were in clinical remission on anti-TNF maintenance therapy, providing novel data and new insights into the significance of various ultrasound parameters during this phase. Nonetheless, our study also has several limitations. The retrospective design and single-center nature, which may introduce selection bias, although this feature also reflects real-life clinical experiences. The cohort is limited to CD treated with anti-TNF and may not be representative of other biological drugs. Furthermore, as the BWT increased, the number of patients included in the analysis decreased. This fact may explain the reduction in significance for wall thicknesses >5 mm. Another limitation relates to the lack of previous IUS data to calculate the BWT response to therapy.

Conclusion

Our study highlights the significant role of BWT as an exclusive ultrasonographic marker for the detection of treatment failure. Using a single objective ultrasonographic parameter simplifies the use of IUS, an important factor that may facilitate the use of this important imaging technique. As the number of novice and less experienced IUS users continues to grow, simplification of the IUS technique can potentially increase the accuracy of IUS and increase the expectancy of IUS. Future prospective studies with larger cohorts are needed to support the results and further validate the merit of BWT as a single reliable marker.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251343008 – Supplemental material for Intestinal ultrasound measurement of bowel wall thickness can be used as a sole marker for defining anti-TNF maintenance therapy failure in Crohn’s disease

Supplemental material, sj-docx-1-tag-10.1177_17562848251343008 for Intestinal ultrasound measurement of bowel wall thickness can be used as a sole marker for defining anti-TNF maintenance therapy failure in Crohn’s disease by Ahmad Albshesh, Shadi Haj, Ido Veisman, Lior Dar, Shomron Ben-Horin, Ohad Regev, Uri Kopylov and Dan Carter in Therapeutic Advances in Gastroenterology

Footnotes

Appendix

Acknowledgements

None.

Declarations

ORCID iDs

Ahmad Albshesh

Ido Veisman

Shomron Ben-Horin

Uri Kopylov

Dan Carter

Supplemental material

Supplemental material for this article is available online.

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