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

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

At the time of treat to target, endoscopic healing is the goal to achieve in ulcerative colitis (UC). Colonoscopy (CO), rectosigmoidoscopy (RS) or rectoscopy can be performed to assess endoscopic healing. The objective of this study was to compare the performance of rectosigmoidoscopy with colonoscopy to predict endoscopic healing (EH) and histological healing.

Aims & Methods

This is a monocentric, prospective cohort of UC patients. All UC patients with a total colonoscopy were included between January 2021 and January 2023. Endoscopic and histological activity were measured using the MAYO endoscopic scores on each colonic segment and the Nancy Score, respectively. The correlation between RS or rectoscopy alone and CO in terms of endoscopic and histological mucosal healing was assessed using Cohen's kappa coefficient.
The study population was calculated according to the following assumptions: (1) absence of rectosigmoidoscopy lesions if absence of total colonoscopy lesions (0%), (2) 10% of lesions not seen in RS, (3) expected difference of 10% between CT and RS. 80 patients had to be included to demonstrate a significant difference in terms of EH between RS and CT with a bilateral alpha risk of 5% and a power of 81%.

Results

80 patients were included. 34 patients were MAYO 0 in RS and CO, 44 were not healed in RS and CO.. The correlation between the two exams was almost perfect with an index к of 0.949 (p=0) for MAYO 0 (2 patients misclassified), and к of 0.945 (p=0) for MAYO 0-1. The correlation between histological healing in RS and CO was almost perfect (к=0.877, p<0.001). Additionally, the correlation between rectoscopy and CT for the evaluation of mucosal healing MAYO 0 and histological healing was almost perfect (к=0.826 (p < 0.001) and к=0.8 (p < 0.001), respectively.

Conclusion

RS is sufficient in UC to assess both endoscopic mucosal healing (whether defined by a Mayo score of 0 or 1) and histological healing. With a false negative rate < 10%, rectoscopy could be a less invasive exam to assess healing in UC.

Introduction

Recently, endoscopic healing (EH) has been recognized as a long term treatment goal for ulcerative colitis (UC)¹. It has been demonstrated that UC does not often remain limited to the mucosa but affects all layers of the bowel². Intestinal ultrasound (IUS) is a useful tool to assess transmural disease in UC³.

Aims & Methods

We performed a retrospective study on UC patients in remission and on stable maintenance treatment with EH (endoscopic Mayo score of ≤ 1) who had an IUS performed between 2 weeks before and 6 months after endoscopic evaluation and had clinical follow up data available for at least 6 months. Patients were identified from 4 prospective cohorts (January 1, 2017 up till December 31, 2023). Clinical follow up data were analysed from date of endoscopy till December 31, 2023.
Transmural healing (TH) measured with IUS was defined as bowel wall thickness(BWT) ≤ 3mm and modified Limberg Doppler score of ≤ 1 on all colonic segments except for rectum. Histology data (healing defined as absence of granulocytes) was also obtained.
Primary outcome was occurrence of any UC related event: documented relapse, initiation of corticosteroids, intensification/change of medical therapy, hospitalization and/or surgery. Patients were censored at first event and time to event analyses with Cox regression was used to determine the association between TH, EH, histological healing and UC related event.

Results

There were 48 patients available for the current analysis. Baseline characteristics are shown in Table 1. The mean duration of follow up was 38.1±13.1 months. Primary outcome occurred in 18/48 patients (37.5%; TH=5, no TH=13). All patients had a clinical relapse as the first UC related event. Subsequently, 4 patients were initiated with corticosteroids, 13 patients had intensification/change of medical therapy and 1 patient had a colectomy. The mean time to event was numerically shorter in patients without TH than in those with TH (67.9±46.4 weeks vs 92.4±61.2 weeks; p=0.370)
Univariate Cox regression showed that TH (HR 0.17, 95% CI 0.06-0.48), endoscopic Mayo score of 0 (HR 0.52, 95% 0.18-1.48) and histological healing (n = 31, HR 0.96, 95% CI 0.26-3.59) were associated with absence of UC related event. However, in multivariate analysis adjusting for age, gender, duration of disease and number of previous biologics and anti-TNF exposure, only TH remained a significant factor (p=0.025) associated with event-free long term outcome. Similar results were observed in analysis involving BWT ≤ 3mm with modified Limberg Doppler score 0.

Conclusion

TH is an independent predictor of favorable long-term outcome for UC patients with EH. This novel finding is currently undergoing validation in larger cohorts.

References

1. Turner, Dan et al. “STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.” Gastroenterology vol. 160,5 (2021): 1570-1583. doi:10.1053/j.gastro.2020.12.031
2. Maaser, Christian et al. “Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis: results from the TRUST&UC study.” Gut vol. 69,9 (2020): 1629-1636. doi:10.1136/gutjnl-2019-319451
3. Ilvemark, Johan F K F et al. “Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement.” Journal of Crohn's & colitis vol. 16,4 (2022): 554-580. doi:10.1093/ecco-jcc/jjab173

Disclosure

Chong-Teik Lim: None.
Christoph Teichert: None.
Maarten Pruijt: None.
Floris de Voogd: received speaker or honoraria fees from AbbVie, Janssen, Galapagos, Pfizer and Takeda.
Geert D’Haens: received research grants from Abbvie, Alimentiv, BMS, J&J, Pfizer, Takeda; consulting fees from Abbvie, Agomab, Alimentiv, AstraZeneca, AMT, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Index Pharmaceuticals, Kaleido, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Progenity, Protagonist, and Ventyx; speaker’s fees from Abbvie, Arena, Boehringer Ingelheim, Celltrion, Galapagos, Gilead, Pfizer, BMS, and Takeda; data monitoring board: Galapagos, AstraZeneca, Seres Health.
Krisztina Gecse: received grants from Pfizer Inc, Celltrion, and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis, and Takeda; and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts.

Introduction

Intestinal ultrasound (IUS), in particular bowel wall thickness (BWT), is accurate in determining endoscopic disease activity in ulcerative colitis (UC). Reduction of BWT six weeks into advanced anti-inflammatory treatment predicted endoscopic response and clinical remission. Filgotinib is a preferential JAK1-inhibitor effective in UC. Currently, there is no data on IUS-kinetics or early prediction of treatment response with filgotinib.

Aims & Methods

In this study, we aimed to identify early IUS predictors of treatment response to filgotinib in patients with moderate to severe UC. This prospective observational study included UC patients with active endoscopic disease (i.e. endoscopic MAYO score (EMS) ≥2) starting with filgotinib. Clinical scores (UCEIS, Lichtiger), biochemical parameters and IUS parameters of the sigmoid were assessed at baseline, after 4 weeks (W4) and at the time of the second endoscopy (between W8 and W23). Endoscopic remission (i.e. EMS=0), endoscopic response (i.e. decrease in EMS ≥1 compared to baseline) and clinical remission (SCCAI ≤2 or Lichtiger score ≤3) were assessed. IUS response (i.e. defined as a reduction in BWT of >25% or >2.0 mm, or >1.0 mm and one colour Doppler signal) was assessed at week 4. All normally distributed data were reported in mean ± standard deviation [SD] and non-normally distributed in median and interquartile range [IQR]. Mann–Whitney U tests were used to compare continuous non-parametric variables, chi square tests for dichotomous variables.

Results

A total of 20 patients were included. 13 patients underwent second endoscopy, 2 refused a follow-up endoscopy and 5 patients were still in follow-up. At baseline, 9 patients (9/20, 45%) had received ≥2 biologicals, 16 patients (16/20, 80%) had previous anti-TNF exposure, and no patients were exposed to other JAK-inhibitors. 8 patients (8/20, 40%) had severe endoscopic disease at baseline (i.e. EMS=3). 5 patients (5/13, 38%) were endoscopic responders at W8-23, and no patient reached endoscopic remission. BWT was significantly lower in the sigmoid colon from W4 onwards for patients reaching endoscopic response (Table 1). Decrease in BWT compared to baseline was statistically greater in endoscopic responders from W4 onwards (Table 1). IUS response was seen at W4 in 6 patients, of which 5 were endoscopic responders (83%, p=0.002). Decrease in BWT from W4 onwards was statistically greater in patients reaching clinical remission at W8-23 (-45% (-55% to -36.6%) vs -9% (-25% to +8%), p=0.014).

Conclusion

On IUS, UC patients treated with filgotinib have significantly lower BWT from week 4 onwards compared to baseline, which could predict endoscopic response.

Disclosure

MP received speakers fees from Janssen and Tillotts
CT received speakers fees from Tillotts
FV received speaker or honoraria fees from AbbVie, Janssen and Tillotts
ML received consultancy/lecturefees from Abbvie, Bristol Myers Squibb , Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda and Tillotts.
RG Received speakers fee from Janssen and Tillotts
GD has served as a consultant and/or received speaker’s fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences.
KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Abbvie, Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Introduction

Ulcerative colitis (UC) is an idiopathic chronic inflammatory bowel disease. The current goal of UC treatment is to modify the natural history of the disease and prevent long-term bowel damage and subsequent disability by using appropriate therapy and monitoring at appropriate intervals.
In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) committee proposed a treat-to-target (T2T) approach and recommended that the therapeutic target in UC should be both clinical and patient-reported outcomes (PRO) remission as well as endoscopic remission with Mayo endoscopic subscore (MES) 0 and 1. However, in STRIDE II, only MES 0 of endoscopic remission is the treatment target and histologic remission is also considered to be a treatment target. Previous studies have demonstrated that patients who achieve an MES of 0 are more likely to have a longer duration of clinical remission than patients without endoscopic remission. Additionally, several studies have shown that histologic remission is a distinct treatment target from endoscopic remission in UC and better predicts clinical remission.
The current treatment target of UC is endoscopic remission with MES 0 as well as clinical remission, but distinguishing between MES 0 and MES 1 is difficult. In our previous study, we demonstrated that histologic activity predicts clinical relapse in UC patients with MES 0 or 1. However, there is no study on whether histologic remission can predict another target, such as endoscopic remission. The aim of this study was to evaluate whether histologic activity can predict the maintenance of endoscopic remission in UC patients with MES 0 or 1.

Aims & Methods

The aim of this study was to evaluate whether histologic activity can predict the maintenance of endoscopic remission in UC patients with Mayo endoscopic subscore (MES) 0 or 1. Four hundred ninety-two UC patients who underwent histologic evaluation at Samsung Medical Center from January 2018 to December 2020 were included in this study. Patients were divided into two groups based on their histologic activity: histologic remission and active. Endoscopic activity was assessed during follow-up, and the primary outcome was endoscopic remission according to histologic activity. Endoscopic remission was defined as an MES of 0, while histologic remission was defined as a Geboes score of < 3.1.

Results

Among the 492 patients, 435 were evaluated for endoscopic activity during the first colonoscopic follow-up, and 146 patients were evaluated during the second follow-up. The median time for the first follow-up colonoscopy was 27.3 months. The histologic active group at index colonoscopy was more likely to experience endoscopic relapse than the histologic remission group (hazard ratio (HR)= 1.63, P < 0.001). In subgroup analysis in patients without clinical relapse, the histologic active group was still more likely to experience endoscopic relapse than the histologic remission group (HR = 1.53, P = 0.030).

Conclusion

The patients who achieve histologic remission are more likely to maintain endoscopic remission compared to those with histologic activity.

References

1. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720-7.
2. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis. 2017;11(6):649-70.
3. Colombel JF, Narula N, Peyrin-Biroulet L. Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel Diseases. Gastroenterology. 2017;152(2):351-61.e5.
4. Dassopoulos T, Cohen RD, Scherl EJ, Schwartz RM, Kosinski L, Regueiro MD. Ulcerative Colitis Care Pathway. Gastroenterology. 2015;149(1):238-45.
5. Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110(9):1324-38.
6. Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-83.

Introduction

Inflammatory bowel disease is an idiopathic disorder characterized by repeated relapses and remissions. Endoscopy, the gold standard for diagnosis and monitoring, is time consuming, expensive and invasive. Fecal calprotectin has been suggested as a surrogate marker to assess intestinal inflammation and predict disease relapse. Published evidence regarding the utility of fecal calprotectin as an indicator of clinical activity and endoscopic severity in patients with inflammatory bowel disease is not unambiguous.

Aims & Methods

The aim of this study was to determine the use of fecal calprotectin as a predictor of clinical activity and endoscopic severity in patients with inflammatory bowel disease.
Methods: Patients fulfilling selection criteria were recruited for the study. Clinical examination findings, laboratory investigations and fecal calprotectin levels were documented as per proforma. Endoscopic and clinical severity were measured by Simple Endoscopic Score and Crohn’s Disease Activity Index for Crohn’s disease and by Ulcerative Colitis Endoscopic Index of Severity score and Simple Clinical Colitis Activity Index for Ulcerative Colitis .Lab investigations and calprotectin were repeated after six months and compared with endoscopic and clinical activity indices.

Results

Fecal calprotectin correlated with Crohn’s Disease Activity Index both at first visit and follow up (r-0.689, p-0.016)(r-0.425, p-value <0.05). The sensitivity and specificity of calprotectin in detecting active disease and remission at first visit were 93.8% and 80% respectively (AUC-0.869). At follow up, the sensitivity and specificity were 80% and 93.3% respectively (AUC-0.867). In Ulcerative colitis , Simple Clinical Colitis Activity Index score correlated with fecal calprotectin levels at first visit and follow up. (r-0.231 / 0.387, p-value 0.001/0.001). The sensitivity of calprotectin in detecting active disease and remission in ulcerative colitis was 92.6% and specificity was 83.3%. AUC was 0.88. At follow up, the sensitivity of fecal calprotectin in detecting active disease and remission was 89.9% and the specificity was 87.0% ; AUC was 0.879.

Conclusion

Fecal calprotectin levels show significant correlation with clinical and endoscopic activity indices in patients of inflammatory bowel disease. Therefore, calprotectin levels in stool could be used as a surrogate marker for monitoring mucosal status as well as predicting endoscopic remission in these patients.

References

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5. Daperno M, Castiglione F, Ridder L, et al. Results of the 2nd part Scientific Workshop of the ECCO. II: measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. J Crohns Colitis. 2011;5:484–98.
6. Canani RB, de Horatio LT, Terrin G, et al. Combined use of noninvasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2006;42:9–15.