Introduction

Clinical response to vedolizumab has been reported as being significantly lower in patients exposed to anti-TNFs [1,2]. However, in most countries anti-TNFs remain the de facto first biologic therapies for patients with Crohn’s disease (CD). After failure of a first Anti-TNF drug, change of class of therapy is increasingly recommended in lieu of a second anti-TNF [3]. Using corticosteroid-free (CSF) remission as the main clinical outcome, we collected data on vedolizumab used as second biologic in CD patients who failed anti-TNF therapies.

Aims & Methods

PubMed and Embase were searched for real world data from cohorts of adult patients with at least 95% of exposure to anti-TNFs, at least 6 months of data, direct access to patients data (no claims database), and CSF remissions (no cumulative data) were selected. Additionally, the use rates of corticosteroids and other concomitant medications at baseline were extracted.

Results

A total of 10 studies met the search requirements, with patient numbers ranging from N=45 to N=161. One author from the Netherlands reported twice on the same registry, only one dataset was retained to avoid counting patients twice. Clinical remission was defined as either a Harvey Bradshaw index of less than or equal to 4 (8 studies) or as a Crohn’s disease activity index score <150 without resort to surgery (1 study). Across studies, the rates of corticosteroid use at baseline varied from 15.5% in a 2017 French cohort to 51.0% in a 2018 US study. Rates of CSF remission at 6 months were not related to baseline corticosteroid use and ranged from 15.3% in a 2020 UK report to 58.2% in a 2021 French cohort. On average, CSF remission at 6 months was achieved in 37.1%, (95% CI 33.6 - 40.5%) of TNF failed CD patients treated with vedolizumab as second line biological therapy [Table]. Clinical remission rates at 6 months were generally higher, but at 1 year, clinical remission and CSF remission rates were almost identical in most cohorts, highlighting the importance of achieving early CSF remission.

Conclusion

Despite anti-TNF failure, a significant proportion of CD patients may respond to vedolizumab and achieve CSF remission, regardless of the baseline use of concomitant corticosteroids. This benefit is established within 6 months after induction.

Table: Rates of clinical remission and corticosteroid-free (CSF) clinical remission in cohorts reported in the literature

Source	Clinical remission	CSF clinical remission	CD patients, N	Clinical remission definition	Baseline concomitant therapies
Amiot A et al. (2017) Alimentary Pharmacology & Therapeutics 46:310–321. France	W6: 31.2% W14: 36.4% W22: 37% W30: 31.8% W54: 30%	W6: 19.1% W14: 30.6% W22: 33.5% W30: 27.7% W54: 27.2%	161	HBI ≤4	Corticosteroids: 15.5% Immunosuppressants (IS): 18.6% Steroids + IS: 6.8% No Steroids or IS: 59%
Christensen B et al. (2018) Inflamm Bowel Dis 24:849–860. US	W14: 38% W30: 62% W52: 51%	W14: 22% W30: 44% W52: 31%	94	HBI ≤4	Corticosteroids: 51% Thiopurines: 29% Methotrexate: 13% Calcineurin inhibitor: 9%
Kolar M et al. (2019) Gastroenterol Hepatol 73:25–31. Czech republic	W30-32: 58.1%	W30-32: 45.2%	45	HBI ≤4	Corticosteroids: 20% Thiopurines/methotrexate: 46.7%
Kopylov U et al. (2019) Digestive and Liver Disease 51:68–74. Israel	W14: 35%	W14: 29% W52: 21%	133	HBI ≤4, CDAI <150	Corticosteroids: 36.8% Immunomodulators: 15.2%
ǂ Biemans VBC et al. (2020) Aliment Pharmacol Ther 52:123–134. The Netherlands		W12: 22.7% W24: 29.7% W52: 26.8%	128	HBI ≤4	Corticosteroids: 31.3% Immunosuppressant (IS): 18.8% Steroids + IS: 15.6%
*Alric H et al. (2020) Aliment Pharmacol Ther 51:948–957. France	W14: 47.7% W48: 37.1%	W14: 34.8% W48: 31.8%	132	HBI ≤4	Corticosteroids: 48.5% Thiopurines 33.3% Methotrexate: 6.8% Other: 2.3% No: 57.6%
*Townsend T et al. (2020) Aliment Pharmacol Ther 52:1341–1352. UK	M2: 16.5% M4: 21.2% M6: 16.5% M12: 25.9%	M2: 11.8% M4: 20% M6: 15.3% M12: 24.7%	85	HBI <5	Corticosteroids: 35.3% Mercaptopurine: 12.9% Azathioprine: 25.9% Methotrexate: 8.2% None: 50.6% Unknown: 2.4%
*Manlay L et al. (2021) Aliment Pharmacol Ther 53:1289–1299. France		W14: 56.8% W24: 58.2% W54: 40.5%	88	CDAI < 150 without resort to surgery	Corticosteroids: 31.8% Thiopurines: 14.8% Methotrexate: 4.6% No Immunosuppressant: 80.7%
ǁOnali S et al. (2022) Am J Gastroenterol 117:1279–1287. Italy	W26:44.8% W52: 55.5%	W26: 40.7% W52: 51.1%	132	HBI ≤4	Corticosteroids: 49.4% Immunomodulators: 9.5%

ǂ Overlaps with Biemans VBC et al. (2020) Clin Pharmacol Ther 107:1189–1199.
*Data from unweighted cohort
ǁ Data from weighted cohort

References

1. Verstockt, B, et al. 2019. “Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients.” Journal of Crohn’s and Colitis 14 (3): 332–41.
2. Gils, A, et al. 2017. “Recent Anti-TNF Exposure Predicts Lower Vedolizumab Trough Concentrations in Patients with Crohn Disease.” Gastroenterology 152 (5): S380.
3. Zhuleku, E, et al. 2022. “Real-World Outcomes Associated with Switching to Anti-TNFs versus Other Biologics in Crohn’s Disease Patients: A Retrospective Analysis Using German Claims Data.” Therapeutic Advances in Gastroenterology 15: 1–13.

Disclosure

Christian Agboton and Dirk Lindner are employees of Takeda and hold stock/options in Takeda.
This study was sponsored by Takeda.
Medical writing support was provide by Paul Hassan of Excel Medical Affairs and was funded by Takeda.

Introduction

In the UK, FIT is offered to adults with symptoms suggestive of colorectal cancer (CRC). A positive result (>10µgHb/g) triggers a referral through a suspected colorectal cancer pathway for further investigation.¹ IBD and CRC share many similar symptoms. However, there is very limited evidence assessing the use of FIT in predicting the onset of IBD, following exclusion of CRC.

Aims & Methods

We aimed to assess the association between abnormal FIT results in symptomatic patients and the risk of new IBD diagnosis within a year, and how this varies with age and faecal calprotectin (FCP) results. This was done through a population-based observational study of all symptomatic FIT recorded in the Clinical Practice Research Datalink (CPRD) between January 2019 and June 2023 with one year follow up.² Patients with prior diagnoses of IBD or CRC were excluded. Kaplan-Meier estimates were used to assess cumulative 1-year IBD risk, stratified by age group, FIT results and FCP results.

Results

2762 (0.58%) of 473402 patients were diagnosed with IBD within 1-year of symptomatic FIT. The risk was 541/377485 (0.1%) in those with a FIT ≤10µgHb/g compared to 2221/95917 (2.3%) with FIT>10µgHb/g. A positive FIT is associated with increased risk of IBD diagnosis (p<0.001) . Table 1 summarises the 1-year risks of new IBD diagnoses within this symptomatic FIT population in strata of age and faecal calprotectin. As can be seen those with a negative FIT have a low risk of IBD diagnosis at all ages regardless of FCP. With rising FIT the risk rises in all age groups and is highest in the under 40s with a FIT >200µgHb/g and FCP >50µg/g at 38.9 % (95% CI: 34.62-43.07%). Even at this level of FIT, cumulative risk is only 3.8% (95% CI: 1.9-5.68%) when FCP ≤50µg/g. In contrast, the cumulative risk of IBD in patients age ≥70 is low, regardless of FIT levels, with 0.05% (95% CI: 0.04-0.07%) risk in those with FIT ≤10µgHb/g and 1.4% (95% CI: 1.16-1.65%) in FIT >200µgHb/g.

Table 1: 1-year cumulative risk of IBD (%)
	FCP ≤50µg/g						FCP >50µg/g
FIT Categories	Age Group (Years)					FIT Categories	Age Group (Years)
	<40	40-49	50-59	60-69	≥70		<40	40-49	50-59	60-69	≥70
>200	3.81 (1.9-5.68)	1.91 (0.24-3.55)	2.74 (0.34-5.08)	1.87 (0-4.41)	0 (0-0)	>200	38.99 (34.62-43.07)	25.91 (20.72-30.76)	19.06 (14.53-23.35)	13.58 (8.84-18.07)	4.52 (2.08-6.9)
100.1 - 200	2.02 (0-4.26)	0 (0-0)	6.47 (0.82-11.8)	0 (0-0)	0 (0-0)	100.1 - 200	34.18 (26.08-41.4)	18.12 (10.76-24.86)	7.43 (2.89-11.76)	6.15 (1.24-10.81)	4.56 (1.41-7.61)
40.1 - 100	2.54 (0.32-4.71)	1.31 (0-3.1)	0.62 (0-1.84)	0.85 (0-2.51)	0 (0-0)	40.1 - 100	21.45 (16-26.56)	12.38 (6.85-17.57)	5.8 (2.41-9.08)	3.2 (0.65-5.69)	1.44 (0.03-2.84)
20.1 - 40	0 (0-0)	0.47 (0-1.4)	0 (0-0)	0 (0-0)	0 (0-0)	20.1 - 40	11.58 (6.91-16.02)	6.64 (2.58-10.54)	1.99 (0.04-3.9)	2.72 (0.34-5.04)	1.96 (0.39-3.51)
10.1 - 20	0 (0-0)	0.69 (0-1.63)	0.35 (0-1.04)	0 (0-0)	0 (0-0)	10.1 - 20	7.75 (4.03-11.33)	4.73 (1.66-7.69)	2.65 (0.69-4.56)	2.39 (0.3-4.43)	0.85 (0-1.81)
≤10	0.1 (0.04-0.16)	0.13 (0.05-0.2)	0.09 (0.02-0.15)	0.11 (0.01-0.21)	0 (0-0)	≤10	2.17 (1.63-2.71)	1.37 (0.92-1.81)	1.17 (0.81-1.53)	0.82 (0.48-1.16)	0.43 (0.21-0.64)

Conclusion

A combination of symptomatic FIT and FCP can stratify the risk of IBD diagnosis. This should lead to prioritisation of those at high risk for early colonoscopy even among the young who are unlikely to have colorectal cancer. Those with low risk of either diagnosis could be spared invasive testing.

References

1. National Institute for Health and Care Excellence. Quantitative faecal immunochemical testing to guide colorectal cancer pathway referral in primary care [DG56]. 2023 24 August 2023 15 April 2025]; Available from: https://www.nice.org.uk/guidance/DG56.
2. Clinical Practice Research Datalink. CPRD Aurum December 2024 (Version 2024.12.001). [Data set] 2024 15/04/2025; Available from: https://www.cprd.com/doi/cprd-aurum-december-2024-dataset.

Introduction

Crohn's disease (CD) is a heterogeneous condition with potentially complicated course. We aimed to evaluate the rates and risk factors for complicated disease course within a real-world, prospective inception cohort of patients with newly diagnosed CD (ndCD).

Aims & Methods

This prospective, longitudinal cohort study included adults with ndCD managed at a tertiary referral center. Treatment decisions were made at the discretion of the treating physician. The key outcomes were: (1) complicated-disease course - defined as CD-related hospitalization, surgery, steroid dependency, or the use of ≥2 biologics; (2) extra-complicated disease course - defined as recurrent or prolonged hospitalization (>5 days), multiple perianal procedures, intestinal resection, steroid dependency, or the use of ≥3 biologics; and (3) phenotype progression. Kaplan-Meier survival analysis was used to assess rates of complicated course over 5 years, and multivariable Cox regression models were applied to identify baseline risk factors.

Results

A total of 192 patients with ndCD were enrolled; 70% presented with an inflammatory phenotype (B1) (see Table 1). Overall, 150 patients (78.1%) were recommended to start biologic therapy, with half receiving this recommendation within 4.1 months (95% CI: 2.1-6.3) from diagnosis. Of these, 134 patients (89.3%) initiated treatment - 50% within 6 months and 63.6% within 12 months. Cumulative outcome rates at 1, 3, and 5 years post-diagnosis were: complicated course - 24.2%, 35.9%, and 51.3%, respectively; extra-complicated course - 15.6%, 20.5%, and 29.0%, respectively; phenotype progression - 1.6%, 5.5%, and 10.6%, respectively. In a multivariable analysis, patients with a progressive phenotype (B2/B3) at diagnosis had significantly increased risk for complicated (HR 3.3, 95% CI:2.0-5.7) and extra-complicated (HR 6.7, 95% CI:3.1-14.4) disease course. Additional risk factors included elevated inflammatory markers and disease extent at diagnosis. We further analysed the subgroup of 33 patients with a B1 phenotype (~25% of those with a B1 phenotype) who were not recommended biologic therapy by their treating physician. In this subgroup, the complicated course was markedly low, 3.0%, 6.3%, and 11.5% at 1, 3, and 5 years, respectively, and none developed an extra-complicated course. Notably, this subgroup exhibited significantly lower inflammatory indices (CDAI, HBI, CRP, and fecal calprotectin) at diagnosis compared to patients for whom biologics were recommended (all p<0.001).

Table 1:

Sex, Female, n (%)	88 (45.8)
Age, median (IQR)	26 (21-36)
BMI (kg/m2), median (IQR)	21.7 (19.9-25.2)
Never smokers, n (%)	139 (72.4)
Family history of IBD, n (%)	58 (30.2)
Extraintestinal manifestations, n (%)	57 (29.7)
Ileal (L1), n (%) Colonic (L2), n (%) Ileocolonic (L3), n (%)	124 (64.6) 19 (9.9) 49 (25.5)
Perianal (P), n (%)	37 (19.3)
Inflammatory phenotype (B1), n (%) Stricturing phenotype (B2), n (%) Penetrating phenotype (B3), n (%)	137 (71.4) 36 (18.8) 19 (9.9)

Conclusion

In this real-world cohort, applying a best-practice treatment approach, over half of patients with ndCD experienced a complicated course within five years, primarily those with a progressive phenotype at diagnosis. Notably, a subset of patients with an inflammatory phenotype and low inflammatory burden had favorable long-term outcomes without biologics, underscoring the importance of early risk stratification to guide individualized treatment strategies.

Introduction

A disturbed intestinal mucosal barrier is crucial in the pathogenesis of chronic inflammatory bowel disease (IBD). A higher susceptibility of patients with IBD to periodontitis (PO) is consistent with a similar pathogenesis. However, PO is often neglected in IBD patients, because their therapy is focussed on the intestinal symptoms.

Aims & Methods

A symptom-orientated score should be developed, which results from the information in a questionnaire that patients answer. A threshold value should indicate PO requiring treatment. A PO score is calculated on the basis of the questionnaire and compared with an objective grading of PO (determined by a clinical assessment). Grade 0 = no PO, grade 1 = mild PO (not requiring treatment), grade 2 = moderate PO, grade 3 or 4 = severe PO. Data was collected from 146 control subjects without IBD, 76 patients with Crohn's disease (CD) and 42 patients with ulcerative colitis (UC).

Results

	Clinical grade of PO	Number	Percent	Mean PO score
Persons without IBD	0 1 2 3 4 total	23 2 36 64 31 146	15.8 1.4 24.7 43.8 14.4 100	9.1
UC	2 3 4 total	12 29 1 42	28.5 69.0 2.4 100	8.7
CD	2 3 4 total	23 46 7 76	30.3 60.5 9.2 100	9.7

The table shows the distribution of clinical PO grades in the 3 groups (No IBD, CD, CU) in absolute numbers and per cent as well as the respective mean PO score. The data of the control group were used for the evaluation of the questionnaire. There was a good correlation between the objective degree of PO and the PO score determined from the patients' statements. The ROC analysis showed that a PO score of 6.75 resulted in a sensitivity of 72.4% and a specificity of 64% for the detection of PO stage ≥ 2. For the detection of a PO stage ≥ 3, a PO score of 7.75 results in a sensitivity of 73.2% and a specificity of 64%. The AUROC was 0.746 and 0.742, respectively. There were no cases with grade 0 or 1 PO in the CD group or UC group, i.e. all had at least moderate/moderate PO. The high prevalence of severe PO, even in people without IBD, can be explained by the fact that most of these people were recruited in a specialised periodontology clinic. Accordingly, the mean PO score is relatively high here.

Conclusion

Our data confirm a high prevalence of higher grade PO requiring treatment in patients with IBD. A higher PO score (from 6.75) can predict with high probability PO requiring treatment, which is often overlooked or neglected in IBD patients. These patients can therefore be referred for integrated therapy.

References

Chang JT. Pathophysiology of Inflammatory Bowel Diseases. New England Journal of Medicine 2020; 383: 2652–2664
Saez A, Herrero-Fernandez B, Gomez-Bris R, Sánchez-Martinez H, Gonzalez-Granado JM. Pathophysiology of Inflammatory Bowel Disease: Innate Immune System. Int J Mol Sci 2023; 24: 1526.
Axelrad JE, Cadwell KH, Colombel J-F, Shah SC. The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review. Therap Adv Gastroenterol 2021; 14: 17562848211004493
Ananthakrishnan AN, Singal AG, Chang L. The Gut Microbiome and Digestive Health – A New Frontier. Clinical Gastroenterology and Hepatology 2019; 17: 215–217.
She Y-Y, Kong X-B, Ge Y-P, Liu Z-Y, Chen J-Y, Jiang J-W, Jiang H-B, Fang S-L. Periodontitis and inflammatory bowel disease: a meta-analysis. BMC Oral Health 2020; 20: 67.
Bertl K, Burisch J, Pandis N, Bruckmann C, Klinge B, Stavropoulos A. Periodontitis prevalence in patients with Ulcerative colitis and Crohn’s disease - PPCC: A case-control study. J Clin Periodontol 2022; 49: 1262–1274.

Introduction

A decade ago, endoscopic surveillance (ES) for Barrett’s oesophagus (BO) was recommended to improve the outcome of oesophageal adenocarcinoma through early recognition and prevention¹. The yield of ES to detect dysplasia may depend on guideline adherence and quality of endoscopy^2,3,4.

Aims & Methods

The aim is to assess whether dedicated (expert) ES (DS) is more effective than conventional (non-dedicated) ES (NS) by means of Key Performance Indicators (KPI), Dysplasia Detection Rate (DDR), use of advanced imaging and complication rate.
This multicentre (5 UK hospitals) retrospective study includes real-world ES data from 1303 procedures conducted within the last 8 years. The endoscopy and histology reports and clinical notes of consecutive procedures were accessed. The data were collected in spreadsheets and then analysed with SPSS-23. Two services were reported demographically and compared with appropriate statistical tests and logistic regression to test factors associated with DDR.

Results

Data from 680 DS and 623 NS procedures were included, comprising 906 (69.5%) males and 397 (30.5%) females (M:F=2.3:1.0). The age ranged from 14-90 yrs with a mean of 63.7 (SD±12.5) yrs. The maximum length of the BO was 18 cm with a mean of 4.1 cm (SD±3.0). There were significant differences in all the KPIs (Prague classification, Barrett’s island description, hiatus hernia delineation, visible lesion documentation, Paris classification, Seattle protocol adherence and inspection time) favoring the DS (P<0.001). Other comparisons: narrow band imaging (NBI, P<0.001), acetic acid chromoendoscopy (AAC, P<0.001), sedation (P=0.02) and acquisition of target biopsies (, P<0.001) were also significantly higher in DS while the complication rate was significantly lower (P=0.05). Importantly, the DDR was significantly higher in DS (58/680 (8.5%)) than in NS (16/623 (2.6%)) with a P<0.001. Regression analysis showed: increasing age, male sex, lesion description and Paris classification documentation were associated with higher DDR (Table 1), while other indicators showed no significant association.

Table 1. Factors associated with dysplasia detection

	Odds ratio	95% CI	P
Age	1.03	1.01 – 1.05	0.002
Sex	1.86	1.16 – 2.98	0.009
Visible lesion documentation	2.23	1.03 – 4.81	0.041
Paris classification	2.19	1.00 – 4.77	0.049

Conclusion

Surveillance for BO through a dedicated service with high quality endoscopy can produce a higher diagnostic yield with improved DDR and a lower complication rate. Given these benefits, large-scale prospective studies are warranted to assess the true impact on mortality, morbidity, cost benefit and patient-reported outcomes, ensuring that surveillance service provides a meaningful clinical benefit, particularly with risk stratification concerning the factors associated with disease progression.

References

1. Fitzgerald et al. (2013). BSG guidelines on Barrett’s oesophagus. Gut, 63(1), 7–42. doi:10.1136/gutjnl-2013-305372.
2. Britton et al. (2019). Improving accuracy in Barrett’s surveillance. Frontline Gastroenterol, 10(2), 128–134. doi:10.1136/flgastro-2018-101019.
3. Ratcliffe et al. (2023). Surveillance service improves dysplasia detection. Frontline Gastroenterol, 15(1), 21–27. doi:10.1136/flgastro-2023-102425.
4. Ratcliffe et al. (2023). Dedicated Barrett’s surveillance vs. standard care. iGIE, 3(1), 58–65. doi:10.1016/j.igie.2023.11.003.