Introduction

Transmural healing (TH) has been proposed as a therapeutic target in Crohn’s Disease (CD) with studies showing a better prognosis than endoscopic healing (EH). However, EH is not always accompanied by TH and vice versa.

Aims & Methods

We aimed to evaluate the endoscopic and radiological factors associated with the discordance between EH and TH, the impact of earlier biological initiation on this mismatch and the long-term effect on prognosis. Multicentric retrospective study in patients with CD under biologic therapy who had a baseline computed tomography enterography (CTE) or magnetic resonance enterography (MRE) before therapy initiation and a follow-up ileocolonoscopy and MRE at 12±6 months. EH was defined as an SES-CD<3 or absence of ulcers and TH as the complete normalization of mural and extra-mural inflammation. All radiologic examinations were reviewed by expert radiologists after a consensus and the analysis was performed by inflamed intestinal segments using the McNemar’s test. The impact of the time of biological therapy initiation was assessed using logistic regression. After 5 years of follow-up, we assessed for the presence of long-term bowel damage defined as the need for intestinal resection or progression in disease phenotype (presence of new stenosis or fistula or worsening of previously existing stenosis or fistula).

Results

84 patients were included (52% females) with a median age at diagnosis of 27 yo (IQR 22-37). Half had ileocolonic involvement, 42% isolated ileal disease and 8% colonic disease; most had inflammatory phenotype before treatment (51%) and a median disease duration of 15 months (IQR 4-84). Almost half of the patients (49%, n=41) achieved EH and of those 63% (n=26) did not achieve TH; 23% (n=19) attained TH, of whom 21% (n=4) did not achieve EH. Most of the patients who achieved EH but not TH had persistent disease in the small bowel when compared to the large bowel (88.5% vs 11.5%, p<0.01). Among patients who achieved EH, 71 intestinal segments with signs of inflammation before treatment initiation were analysed. Only the presence of a stricture had a non-significant variation with therapy when compared with the baseline assessment (Table 1). Among the endoscopic variations in patients who achieved TH, only the presence of endoscopic stenosis did not achieve a significant variation and remained persistent (Table 1). There were no differences according to the time of initiation of biological therapy. The persistence of a radiological stricture in patients with EH was associated with long-term bowel damage (13% vs 67%, p=0.02).

Table 1 – Persistent radiological and endoscopic lesions in patients with EH and TH, respectively.

Conclusion

In patients with CD who achieved EH, the persistence of radiological lesions is frequent and does not seem to be modified by earlier biological therapy. The persistence of a radiological stricture is associated with long-term bowel damage. The evaluation of the endoscopic changes in patients with TH was limited by the small sample size.

Introduction

There is an increasing diversification in the treatment landscape for Crohn’s disease (CD) driven by heterogeneity of individual phenotypes, disease courses and previous treatments. This complexity makes universal evidence-based algorithms challenging. A “treat-to-target approach” with tight inflammation monitoring after starting biologics or small molecules therapy is recommended. Intestinal ultrasound (IUS) has proven effective in monitoring treatment response in large CD cohorts. Transmural healing (TH) is a robust but puzzling endpoint that can be achieved in about one-fourth of patients treated with biological therapy and few prognostic indicators to predict it were analyzed.

Aims & Methods

We aimed to describe treatment patterns and effective therapeutic sequences to achieve TH. Secondary aim was to identify prognostic factors to predict TH. This retrospective analysis included CD patients treated with biological and small molecules therapies according to the ECCO recommendations. Patients received biological and small molecules therapies across up to four treatment lines. Biological and small molecules treatment pathways prior to achieve TH were visualized using a Sankey diagram. IUS outcomes were evaluated one year after each biological and small molecules therapy. Logistic regression analysis was performed to identify clinical predictive factors of TH, that was defined as bowel wall thickness <3 mm and no vascularization at IUS.

Results

Among 139 patients treated with biological and small molecules therapies, TH was achieved in 25.9% (n = 36). Infliximab was used as the first-line agent in 55 patients (39.6 %), adalimumab in 69 (49.6%), vedolizumab in 6 (4.4%), certolizumab pegol in 1 (0.7%), Ustekinumab in 8 (5.7%). Twenty-five patients (20%) achieved TH after the first-line therapy (n=10 with infliximab; n=9 with adalimumab; n=3 with vedolizumab; n=3 with ustekinumab). TH rates declined with each additional line of therapy. The median time to achieve TH was 25.6 months (range 12–60). Treatment sequencing analysis revealed a progressive shift toward ustekinumab in later lines, with anti-TNFs remaining the most frequent first-line agents. Multivariate analysis showed that colonic lesion and early treatment (within 2 years from diagnosis) were associated with a higher likelihood of achieving TH [OR = 7.76, p<0.001; OR 6.705, p<0.001, respectively], while perianal disease was associated with a lower likelihood of TH [OR 0.151, p=0.02].

Conclusion

This study highlights a progressive decline in TH rates with successive lines of biological and small molecule therapies in CD patients and identifies several clinical factors that influence this outcome. Long-term follow-up and prospective studies specifically designed to evaluate sequencing in patients exposed to anti-TNFs are needed to guide challenging decisions.

Introduction

Transmural healing is a promising target in Crohns’ disease (CD) that is associated with more favorable outcomes than endoscopic remission, especially lower risk of bowel damage progression. C-score has been recently developed and validated to assess transmural healing in patients with CD. However, the best time to assess transmural healing remains to be determined.

Aims & Methods

We aimed to evaluate the kinetics of transmural healing in patients with CD treated with anti-TNF therapy.
From a prospective database of patients with CD performing MRI for luminal CD, we analyzed the kinetics of transmural healing among CD patients older than 18 years-old receiving anti-TNF therapy, with objective sign of inflammation on morphological evaluation (cross-sectional imaging) before starting the treatment, who underwent at least one MRI examination to assess therapeutic efficacy within 12 months. Patients treated with anti-TNF agents for treat isolated perianal lesions were excluded.
We used a statistical model based on imputation according the last observation carry forward and clinical relevance. Transmural healing was then assessed every month during the first year. For segmental analysis, we used the same division into segments than recommended for Lemann Index calculation. Transmural healing was defined as C-score < 0.5 in each segment. C-score was calculated as previously published (0.2 x (bowel thickness in mm – 3) + 2 if ulcer + 1.5 if enlarged lymph nodes).

Results

Overall, 123 patients were included. Among them, 90 were female (73.1%), 48 (39.9%) were current smokers and 53 (43.0%) had prior intestinal resection. The median CD duration at baseline was 7.6 years [1.4-15.2]. At baseline, 41 patients (33.3%) were anti-TNF-naïve. At baseline, 67 patients (55.3%), 53 patients (43.8%) and 1 patient (0.8%) were treated with infliximab, adalimumab and golimumab, respectively with concomitant immunosuppressant in 94 patients (79.0%).
At baseline, 220 segments were considered as active (C-score > 0.5) including 100 in the terminal ileum and 120 in the colon/rectum.
According per-segment analysis (N=220), the rate of transmural healing was 6.4% at M1, 6.4% at M2, 10.0% at M3, 10.1% at M4, 14.6% at M5, 18.0% at M6, 23.2% at M7, 24.5% at M8, 26.0% at M9, 26.8% at M10, 29.1% at M11 and 30.4% at M12.
Among terminal ileum segments (n=100), the rate of transmural healing was 2.0% at M1, 2.0% at M2, 5.0% at M3, 5.0% at M4, 9.0% at M5, 12.9% at M6, 16.0% at M7, 17.0% at M8, 18.0% at M9, 19.0% at M10, 20.0% at M11 and 20.0% at M12.
Among colorectal segments (n=120), the rate of transmural healing was 6.4% at M1, 6.4% at M2, 13.8% at M3, 13.8% at M4, 15.6% at M5, 22.0% at M6, 28.4% at M7, 28.6% at M8, 28.6% at M9, 28.6% at M10, 32.8% at M11 and 34.4% at M12.
Among the 123 patients with CD, in multivariable analyses, absence of transmural healing (C-score > 0.5) within the first year was associated with increased risk of surgery (HR=3.37 [1.30-8.68]; p=0.012), drug discontinuation (HR=2.31 [1.29-4.14]; p=0.005), and bowel damage progression (p <0.001) while we observed a trend for higher risk of CD-related hospitalization (HR=1.92 [0.85-4.36]; p=0.11).

Conclusion

Transmural healing is achievable in more than 30.0% of active segments in patients with CD treated with anti-TNF therapy within the first year. The best time to assess transmural healing was between 6 and 12 months after starting anti-TNF therapy with higher rate of transmural healing for colorectal versus ileal segments. Transmural healing defined as C-score < 0.5 is associated with long-term improved outcomes in patients with CD.

Disclosure

Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda

Introduction

Data on the long-term benefit of transmural healing (TH) are scarce in children.

Aims & Methods

We investigated the outcomes of pediatric Crohn's disease (CD) patients with TH comparing them to those with mucosal healing (MH) and with “no healing”.
We conducted a prospective, single-center, observational study conducted at the Pediatric Gastroenterology Unit of Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy within a 3-month interval were consecutively enrolled. TH was defined as the complete healing of both the mucosa at endoscopy and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months number disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications were collected.

Results

93 children were included (mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. The risk of any unfavorable outcome was lower in both TH and MH patients compared to NH (Log Rank p<0.0001 and p=0.002). Children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p<0.0001 and p=0.0002, respectively) compared to NH. TH and MH patients were comparable for all the outcomes evaluated.

Conclusion

Achieving TH in pediatric CD is associated with better outcomes, although the additional benefit over MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.

Introduction

The STRIDE II guidelines recognize endoscopic healing as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, transmural healing could reduce the risk of long-term complications. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic and ultrasound healing.

Aims & Methods

We conducted a prospective study that included all patients with CD in clinical remission who underwent colonoscopy with endoscopic healing (CDEIS <4) and intestinal ultrasound (IUS) within 4 weeks between September 2019 and September 2022. IUS transmural healing was defined by a parietal thickness < 3 mm on all digestive segments (colonic and ileal) without color doppler signal.
The primary endpoint was CD relapse, defined as the need for drug intensification, initiation of corticosteroid therapy, CD-related hospitalization, development of a perianal and luminal fistula or abscess, or the need CD-related bowel surgery. Patients were followed up at least every 6 months for two years.

Results

A total of 93 patients were included, the majority of whom were women (53%) with ileocolonic location (43%). The median disease duration was 12 years (IQR, 4-19) and 71% patients were treated with anti-TNF. Ultrasound transmural healing was observed in 73% (68/93) of patients. After a median follow-up of 22.5 months [IQR, 19.3-23.7] 26% of patients have relapsed. The risk of relapse was significantly higher among patients IUS activity at 6 and 12 months (13% vs. 5% and 24% vs 8 % p = 0.007). In multivariate analysis, the risk of relapse was 3 times higher without IUS transmural healing (HR 3.07 (1.35-9.97); p = 0.007). Among patients with a complete endoscopic healing (CDEIS 0) the relapse rate were also significantly higher among patients with IUS activity compared to those with IUS healing (HR 3.65 (1.06-12.8); p =0.040).

Conclusion

IUS transmural healing was associated with a lower risk of relapse among patients with endoscopic healing and could be considered as a non-invasive therapeutic target in CD.

Introduction

Endoscopic scores are crucial for assessing Crohn's disease (CD) severity, guiding therapy, and monitoring progression. The Simplified Endoscopic Score for Crohn's Disease (SES-CD) is widely used for this purpose [1]. Accurate scoring is vital for patient care. Recently, artificial intelligence has demonstrated potential in medical image interpretation [2]. This study aims to evaluate ChatGPT's effectiveness in rating the SES-CD.

Aims & Methods

This retrospective study evaluated ChatGPT's accuracy in assessing CD endoscopic activity using the SES-CD. One representative still image was selected for each bowel segment, and stricture degrees were provided separately if present. ChatGPT scored the SES-CD based on these images. The IBD expert's ratings were validated by calculating the intra-class correlation coefficient (ICC) with clinical trial central readers. The ICC between the IBD expert and ChatGPT scores was calculated to determine ChatGPT's reliability in SES-CD scoring.

Results

Nine (mean age 32.0 ± 11.8 years, 77.8% male) were included, with 45 bowel segments. Three (33.4%), 5 (55.6%), and 1 (11.1%) had nonstricturing nonpenetrating, structuring, and penetrating disease, respectively. Four (44.4%) had ileal disease and 5 (55.6%) had ileocolonic disease. Five (55.6%) had previous IBD surgery.
The SES-CD scores of the participants, rated by IBD expert in the hospital, revealed the following mean and standard deviation for each segment of the bowel: 6.9 ± 2.3 in the ileum, 1.3 ± 2.6 in the right colon, 1.6 ± 2.4 in the transverse colon, 1.3 ± 2.6 in the left colon, and 1.3 ± 2.6 in the rectum. The total SES-CD score was 12.4 ± 10.9. The score reliability of the institute IBD expert was tested compared to the clinical trial central reader and an intraclass correlation coefficient was calculated and found to be 0.96 (95% CI, 0.84-0.99) which is considered extremely correlated.
The mean and standard deviation of ChatGPT score in each segment were: 6.4 ± 2.4 in the ileum, 2.4 ± 3.8 in the right colon, 0.9 ± 2.7 in the transverse colon, 0.3 ± 1.0 in the left colon, 0.6 ± 1.3 in the rectum, with total SES-CD score of 10.6 ± 6.8. The calculated ICC between the expert and ChatGPT obtained SES-CD scores was 0.80 (95% IC, 0.64- 0.89) which is considered highly correlated.

Conclusion

Despite being based on only one photo per segment, ChatGPT demonstrated satisfactory performance in estimating endoscopic activity in CD. The differences between the IBD expert obtained scores and ChatGPT scores were acceptable, suggesting that artificial intelligence has the potential to be a useful tool in clinical and research settings, providing an accurate estimation of disease severity based on limited visual data.

References

1- Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
2- Levartovsky A, Albshesh A, Grinman A, et al. Enhancing diagnostics: ChatGPT-4 performance in ulcerative colitis endoscopic assessment. Endosc Int Open. 2025;13:a25420943. Published 2025 Mar 14.