Introduction

Crohn's disease (CD) is associated with disability by affecting physical and emotional well-being, and by altering social interactions. In the era of treat to target, endoscopic remission has become the therapeutic target to prevent parietal destruction and disability. A deeper remission such as transmural healing would reduce long-term complications related to CD. The impact of transmural healing on disability is currently unknown.

Aims & Methods

We conducted a monocentric cross-sectional study between September 2019 and January 2022. Patients followed for CD in endoscopic remission (CDEIS <4) who underwent within < 4 weeks an intestinal ultrasound (IUS) and a disability assessment by an IBD-disk were consecutively included. Four groups were considered: (A) transmural healing defined by the combination of complete endoscopic healing (CDEIS=0) and ultrasound healing (bowel wall thickness (BWT) less than 3 mm), (B) complete endoscopic healing, (C) ultrasound healing and (D) no healing. Moderate to severe disability was defined as an overall score ≥ 40.

Results

A total of 85 patients were included. Forty-four (51.7%) were female, the median age and disease duration were respectively 38 years (interquartile range [IQR], 33-44) and 12.0 years (IQR, 5-20). There was no difference between the four groups in terms of age, sex, BMI, smoking status, disease location or phenotype or number of biologics failure. The median global IBD-Disk score was 25 (IQR, 9-41) and 24 patients (28.2%) had moderate to severe disability. Transmural healing (group A) was observed in 40 patients (47.1%). Moderate to severe disability was identified in 17.5% (7/40) of patients with transmural healing, 25% (4/16) with endoscopic healing, 44.4% (8/18) with ultrasound healing and 45.4 % (5/11) without healing. In univariate analysis, transmural healing reduced the risk of severe disability (group C vs A OR = 3.77, 95% CI [1.10, 13.45], p = 0.035), group D vs A OR = 3 .75, 95% CI [0.91, 17.12], p=0.063). There was no difference in terms of severe disability between patients with transmural healing and complete endoscopic healing (group B versus A OR = 1.57 95% CI [0.36, 6.23], p = 0.525)

Conclusion

Transmural healing did not provide any benefit in terms of disability compared to complete endoscopic healing. Mucosal healing therefore remains the objective to be achieved in order to reduce the risk of short-term disability.

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

The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score <3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete EH could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of EH achieved.

Aims & Methods

We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment between September 2019 and September 2022 in three centers and were compared outcomes of patients with complete EH (CDEIS = 0) vs partial EH (CDEIS greater than 0 but less than 4). The primary endpoint was therapeutic failure, defined as the need for drug intensification and/or corticosteroid initiation and/or CD-related hospitalization and/or development of a luminal strictures/fistula and/or perianal CD and/or the need for intestinal resection.

Results

A total of 128 patients were included with a median disease duration of 10 (IQR, 4-18) years. Fifty-six (43%) patients had ileocolonic location and 79 (62%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 12 months (8.3-24.3) prior to colonoscopy and 81 (63%) patients had complete EH. After a median follow-up of 22.5 months [IQR, 19.3-23.7], therapeutic failure was observed in 40 patients (31%). The risk of therapeutic failure was significantly higher among patients with partial EH group (25% vs. 43% p = 0.036, HR = 1.90; IC95% = [1.02 - 3.53]; p=0.043). The risk of CD-related hospitalizations (2.5% vs. 17%), p=0.005, HR= 7.09; IC95% = [1.51 – 33.4]; p=0.013) was significantly higher in patients with partial EH. The risk of intestinal resection, steroid initiation and drug intensification among patients with complete and partial EH, were 0% vs. 4.3% (p=0.13), 2.5% vs. 11% (p=0.1) and 22% vs. 36% (p=0.088), respectively.

Conclusion

This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer hospitalizations and an overall decreased risk of treatment failure.

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

Endoscopy is still the gold-standard to assess disease activity in Crohn's disease (CD). Its invasiveness, acceptability and cost limit its use in the era of tight control and treat-to-target. Fecal calprotectin and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. The objective of this study was to evaluate the performance of IUS and fecal calprotectin to assess mucosal healing in CD.

Aims & Methods

All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or calprotectin within 4 weeks between September 2019 and April 2022 were included in a prospective cohort. Bowel wall thickness (BWT) and color doppler signal (CDS) were assessed on each segment. Endoscopic mucosal healing was defined by a CDEIS score < 3.

Results

A total of 153 patients were included, of whom 122 had endoscopic mucosal healing. Eighty-two (53.6%) were female, the median age and disease duration were respectively 36 years (IQR, 28-46) and 10 years (IQR, 4-19). Respectively 56 (56/120, 46.7%) and 93 (93/120, 77.5%) patients presented a BWT < 3 mm and an absence of CDS. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of BWT < 3 mm to predict endoscopic mucosal healing were 56%, 88%, 95% and 36% (patients misclassified as endoscopic mucosal healing 2.5%). The association of an absent of CDS with a normal BWT did not modify the performances. For a calprotectin < 250 µg/g , The Se, Sp, PPV and NPV were respectively 91%, 63%, 90% and 67% for (patients misclassified 8%). The association of a calprotectin < 250 µg/g, with a BWT < 3 mm and the absence of CDS increased the specificity and the PPV (Se 58%, Sp 95%, PPV 97%, VPN 43%, patients misclassified 1%).

Conclusion

Ultrasound is an efficient non-invasive tool to identify patients with Crohn's disease who have achieved endoscopic mucosal healing.

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

In the "treat-to-target" era, the development of non-invasive markers to assess endoscopic healing in ulcerative colitis (UC) is essential. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are alternatives to colonoscopy to assess UC activity. The objective of this study was to evaluate the performance of IUS and FC to assess endoscopic mucosal healing in UC patient.

Aims & Methods

All consecutive patients between January 2021 and August 2022 with UC who underwent (1) a complete colonoscopy (2) an intestinal ultrasound and/or (3) a fecal calprotectin (4) within 4 weeks were included in a prospective cohort. Bowel wall thickness (BWT) and color doppler signal (CDS) were assessed on each segment. Endoscopic mucosal healing was defined by a MAYO score of 0-1.

Results

A total of 57 patients were included, 57.9% had endoscopic healing (22/57 MAYO 0 and 11/57 MAYO 1). Thirty-two (56.1%) were female, the median age and disease duration were respectively 43 years (IQR, 30-58) and 29 years (IQR, 18-39). Respectively 16 (16/57, 28.1%) and 41 (41/57, 71.9%) patients had BWT < 3 mm and an absence of Doppler signal. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of BWT < 3 mm to predict endoscopic mucosal healing were 37%, 77%, 72% and 44%. The association of the absence of CDS with normal BWT did not modify these performances. The same values for fecal calprotectin < 150 µg/g were respectively 81%, 78%, 84% and 74%. The association of a fecal calprotectin < 150 µg/g, with a BWT < 3mm and the absence of Doppler signal increased the specificity and the PPV (Se 33%, Sp 94%, PPV 89%, VPN 48%). The same values were found for patients classified as MAYO 0 or MAYO 0-1 .

Conclusion

The combination of intestinal ultrasound and fecal calprotectin is effective to identify endoscopic mucosal healing in UC. A stricter definition of ultrasound healing could improve the performance of this tool.

Disclosure

No disclosure with this abstract