Introduction

As the therapeutic armamentarium for inflammatory bowel diseases (IBD) is rapidly expanding, it is of increasing importance to optimize treatment sequencing. However, head-to-head trials comparing efficacy of vedolizumab (VDZ) in bio-naïve versus bio-experienced patients are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ in bio-naïve versus bio-experienced patients with IBD in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model (CRM) were applied.

Results

A total of 84 patients were treated with VDZ, 42 bio-naïve and 42 bio-experienced. At baseline, significantly more bio-experienced patients had prior intestinal resection (IR) (40.5% (17/42) vs. 16.7% (7/42), P=0.016), used an immunomodulator (IMM) (35.7% (15/42) vs. 16.7% (7/42), P=0.047) and had a longer disease duration (12.5 vs. 3.5 years, P<0.001). Bio-naïve patients had more moderate to severe comorbidities (21.4% (9/42) vs. 2.4% (1/42), P=0.007). After VDZ induction, CRp rate was higher in bio-naïve patients (60.9% (39/42) vs 39.1% (25/42), P<0.001). Multiple logistic regression analyses revealed that bio-naïve patients had a higher chance reaching CRp (aOR 14.69, 95%CI [3.12-69.14], P<0.001)(table). CRm was reached in 35.7% bio-naïve and 19% bio-experienced patients (P=0.087). No significant difference in BRp (P=0.932) or BRm (P=0.730) rate was found . A significantly higher ERp rate was seen in bio-naïve patients (90.3% (28/31) vs. 66.7% (18/27), P=0.027). Multiple logistic regression analyses showed a trend towards higher ERp rate in bio-naïve patients (aOR 4.65, [0.99-21.84], P= 0.051)(table). No significant difference was seen for ERm (32.3 % (10/31) vs. 11.1% (3/27), P=0.054). After 1 year of VDZ, CRp was significantly higher in bio-naïve patients (82.9% (34/41) vs. 62.5% (25/40), P=0.039). Multiple logistic regression analyses showed no significant difference between both groups. Univariate analyses showed significantly higher CRm rate in bio-naïve patients (70.7% (29/41) vs. 37.5% (15/40), P=0.003). After adjustment for age, disease duration, IMM use and prior IR, this difference was no longer significant. Patients without prior IR had significantly higher odds of reaching CRm (aOR 4.33,[1.13-16.59], P=0.032). No significant difference was seen for BRp (P=0.443) and BRm (P=0.313), nor for ERp (P=0.184) or ERm (P=0.061) in univariate analyses. Cox regression analysis showed significantly longer treatment survival in bio-naïve patients (aHR 2.32, [1.03-5.23], P=0.043).

Conclusion

In this tertiary real-world cohort of patients treated with VDZ, overall, a better efficacy was seen in bio-naïve compared to bio-experienced patients.

Disclosure

No conflict of interest

Introduction

IL-33/ST2 axis and gut microbiota are important factors in the pathogenesis of IBD with a potential reciprocal influence. IL-33/ST2 axis controls the mucosal healing process during intestinal inflammation. Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis (UC) refractory to medical therapies. Pouchitis, the most common complication, is the inflammation of the pouch with a controversial etiology.

Aims & Methods

We aimed to explore the potential role of IL-33/ST2 and gut microbiota axis in the inflammatory process of pouchitis.
30 UC patients with ileal pouch-anal anastomosis were enrolled. After clinical, endoscopic and histological assessment 18 showed pouchitis and 12 a normal pouch. Mucosal samples were collected from the afferent ileal loop and from the pouch and processed for cytokines assessment, histological evaluation and gut microbiota analyses. Multiplex analysis for inflammatory and regulatory cytokines was performed. ELISA and western blot were run to assess IL-33/ST2 protein levels and to evaluate protein isoforms, respectively. IHC was done to evaluate mucosal IL-33/ST2 expression and localization. Microbiota was analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Pouchitis Disease Activity Index and Pouchitis Histological Score were calculated, and CRP and fecal calprotectin were obtained for each patient. Multivariate analyses were run to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches.

Results

IL-1Ra, IL-6, IL-8, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b resulted increased in inflamed pouch vs. normal pouch. No differences were registered between samples obtained from the afferent ileal loop. In pouchitis, IL-7 resulted reduced in the inflamed pouch vs. the afferent ileal loop. In pouchitis, IL-33 and ST2 protein levels were reduced in the pouch vs. the afferent ileal loop and resulted overall decreased vs. patients with normal pouch indicating a potential IL-33/ST2-mediated defective healing process. Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased in only patients with pouchitis. IHC confirmed these observations. IL-33 and ST2 staining was less intense within the inflamed and ulcerated mucosa of pouchitis patients compared to normal pouch, and in close proximity to areas of re-epithelialization. An overall decreased biodiversity in patients with pouchitis vs. patients with normal pouch (both at pouch and afferent ileal loop level) was shown. Lower levels of Verrucomicrobia and increased abundance of Actinobacteria were recorded in inflamed pouch vs normal pouch. In pouchitis, the afferent ileal loop and the pouch showed significantly decreased levels of Akkermansia muciniphila and augmented abundance of Collinsella vs. samples obtained from patients with normal pouch. In pouchitis, multivariate analyses evidenced a significant inverse correlation between Collinsella e Collinsella aereofaciens abundance and ST2 levels.

Conclusion

In patients with pouchitis vs patients with normal pouch divergent inflammatory molecular pathways and microbial populations distinctly characterize the pouch and the afferent ileal loop. Overall, our results suggest a potential role for IL-33/ST2 and gut microbiota axis in driving the gut mucosal wound healing in patients with ileal pouch-anal anastomosis. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Nowadays, Non-Alcoholic Fatty Liver Disease (NAFLD) is a leading cause of liver disease and liver transplantation. Although obesity is a well-recognized risk factor for NAFLD, there are data to support that not all patients with NAFLD are necessarily obese. However, the evidence on the prevalence and risk factors for NAFLD in lean individuals with Inflammatory Bowel Disease (IBD) is scarce.

Aims & Methods

The aim of the study was to assess the prevalence and risk factors for NAFLD in lean population with IBD. This is a cross-sectional, case control study including lean individuals with IBD (cases) and lean individuals without IBD (controls), matched for age and sex. Patients with risky alcohol consumption, previous diagnosis of chronic liver disease (immune, viral, genetic) and secondary causes of NAFLD were excluded. All included patients were performed a liver ultrasound, transient elastography and laboratory tests. Lean individuals were defined as Body Mass Index < 25 kg/m², and NAFLD as ultrasound steatosis and/or Controlled Attenuation Paremeter >248 dB/m. A descriptive analysis was carried out, and the relationship between variables was assessed using Chi square test/Fisher´s test (categorical variables) or T-student/Mann-Whitney U test (quantitative variables), as appropiate. In addition, a multivariate analysis was performed, presented as adjusted Odds Ratio (OR) and 95% Confidence Interval (95%CI).

Results

A total of 443 participants, 363 lean cases and 80 lean controls, were included in the study. No differences were observed in terms of age, sex and metabolic risk factors between both groups (Table 1). The prevalence of NAFLD in lean individuals with IBD was significantly higher compared to lean individuals without NAFLD (22% vs. 10%, p=0.015). Multivariate analysis confirmed that IBD was an independent risk factor for NAFLD in lean population (OR 2.75 95%CI (1.18-6.41)). In addition, male sex (OR 1.78 95%CI (1.04-3.05)) and older age (OR 1.03 95%CI (1.01-1.05)) were identified as risk factors for NAFLD in lean individuals.

Table 1. Baseline characteristics of cases and controls.

Conclusion

The prevalence of NAFLD is significantly higher in lean population with IBD, suggesting that IBD could play a role in the development of NAFLD in lean individuals.

Disclosure

This project has received funding from “Diputación General de Aragón” (code: DGACOVID-02).

Introduction

The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly increasing recent years with newer therapies such as vedolizumab (VDZ). Their effectiveness has already been demonstrated against placebo, but head-to-head trials compared to tumour necrosis factor alpha inhibitors (anti-TNF) are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ versus anti-TNF in bio-naïve IBD patients in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ and anti-TNF at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model were applied. Propensity scores for VDZ vs. anti-TNF were weighted for age at start biological, IBD type, perianal disease activity, disease duration and previous IBD-related intestinal resection.

Results

In total, 42 patients received VDZ and 57 anti-TNF. At baseline, the VDZ group had an older median age (38 vs. 31 years, P=0.024), longer disease duration (P=0.017) and more moderate to severe comorbidities (21.4% (9/42) vs. 0% (0/57), P<0.001). In the anti-TNF group, percentage of CD patients was higher (77.2% (44/57) vs. 57.1% (24/42),P=0.034), patients had more upper GI, penetrating or stricturing disease (P=0.013 for location and P=0.004 for behavior), perianal disease (P=0.034) and used more immunomodulators (IMM) during treatment (52.6% (30/57) vs. 16.7% (7/42), P<0.001). After treatment induction, CRp (P=0.311) and CRm (P=0.216) rate was not significantly different. The anti-TNF group had a significantly higher BRp rate compared to the VDZ group (87.8% (43/49) vs. (23/34), P=0.026). After adjusting for propensity score, age, IBD type, systemic corticosteroid (CS) or IMM use, the higher rate of BRp remained (aOR 3.83 [1.01-14.60], P=0.049). Similar results were found for BRm (87.8% (43/49) vs. 67.6% (23/34), P=0.026). After adjustment for the same confounders, the higher rate of BRm in the anti-TNF group remained (aOR 3.83 [1.01-14.60], P=0.049). No significant difference was seen for ERp (P=1.000) and ERm (P=0.338). After 1 year, univariate analysis showed no significant difference for CRp (P=0.736) and CRm (P=0.404), nor for BRp (P=0.907) and BRm (0.890) or for ERp (P=0.163) and ERm (P=0.533). Treatment survival using Cox regression model with adjustment for propensity and IMM or CS use, showed no significant longer treatment duration for anti-TNF compared to VDZ (aHR 0.947 [0.36-2.49], P=0.913).

Conclusion

In this tertiary real-world cohort of bio-naïve patients with IBD, anti-TNF and VDZ showed a similar efficacy, with an advantage of anti-TNF regarding onset of action.

Introduction

As the therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly expanding, it is of increasing importance to optimize treatment sequencing. However, head-to-head trials comparing efficacy of tumor necrosis factor alpha inhibitors (anti-TNF) in bio-naïve and bio-experienced patients (not compared to placebo), are scarce.

Aims & Methods

Aim: To compare the effectiveness of anti-TNF (infliximab and adalimumab) in bio-naïve versus bio-experienced IBD patients in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with anti-TNF at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model were applied.

Results

A total of 114 patients were treated with anti-TNF, 57 bio-naïve and 57 bio-experienced. At baseline, significantly more bio-experienced patients had moderate to severe comorbidities (12.3% (5/57) vs. 0% (0/57), P=0.013) and longer disease duration (4 vs. 1 year, P<0.001). Montreal classification for location in Crohn’s disease (CD) was significantly different (P=0.024), as there were less patients with L3 and more patients with L4 in bio-naïve vs. bio-experienced patients. After induction of therapy, no difference could be found for CRp and CRm for both groups (P=0.364 and P=1.000 respectively). Bio-naïve patients had a significantly higher BRp (87.8% (43/49) vs. 68.6% (35/51), P=0.021). Multiple logistic regression showed a significant higher BRp rate for patients treated for CD vs. UC (aOR 3.17 95% CI[1.03-9.78], P=0.045). Same results were found for BRm (87.8% (43/49) and 64.7% (33/51) for bio-naïve vs. bio-experienced, P=0.007). Multiple logistic regression showed a significant higher BRm in bio-naïve patients (aOR 3.72 [1.21-11.48], P=0.022) and in patients treated for CD vs. UC (aOR 3.48 [1.14-10.60], P=0.028). ERp (P=0.377) and ERm (P=0.707) were not significantly different. After 1 year, no difference could be found for CRp (P=0.126). Significant more bio-naïve patients reached CRm (78.2% (43/55) and 60.4% (32/53), P=0.045). Multiple logistic regression could not withheld this difference after adjustment. No significant difference was seen for BRp (P=0.954) and BRm (P=0.367). More bio-naïve patients reached ERp (81.3% (26/32) vs. 54.1% (20/37), P=0.017). Multiple logistic regression showed a just not significant higher ERp rate in bio-naïve patients (aOR 4.99 [1.00-24.86], P=0.050). Age had a significant influence on ERp (aOR 0.93 [0.874-0.996], P=0.039). No difference could be found for ERm (P=0.227). Regarding treatment survival using Cox regression model, no significant difference could be found for both groups (aHR 1.54 [0.71-3.32], P=0.273).

Conclusion

In general, in this tertiary real world cohort of patients with IBD, the effectiveness of anti-TNF did not differ significantly between bio-naïve and bio-experienced patients.

Introduction

Percutaneous transesophageal gastrotubing (PTEG) was established as an alternative route to access the gastrointestinal tract for the patients that Percutaneous Endoscopic Gastrostomy was contraindicated. PTEG will be an ideal method of tube feeding for the patients without indication of PEG.

Aims & Methods

The aim of this study is to evaluate the clinical usefulness of PTEG for the patients who need tube feeding. A rupture-free balloon (RFB) catheter is inserted into the upper esophagus. Percutaneous balloon puncture with a specialized needle is then performed from the left side of patient’s neck under ultrasonographic control. A guide wire is inserted through the needle into the RFB, followed by a dilator and sheath. A placement tube is then inserted through the sheath, and the sheath is removed. Double Balloons equipped Over tube type RFB were used instead of primary RFB in thirty-five cases that the puncture needle is punctured into the over tube trough the balloon. We perform PTEG in a total of 115 patients (78 men and 37 women, mean age 77.7 years) in whom PEG was not feasible for nutrition. Sixty-one patients had prior gastrectomy , 30 patients had gastric herniation into the thoracic cavity , 6 patients had there stomach located behind the colon , 4 patients had ventriculo-peritoneal shunt tube in front of the stomach and 4 patients had peritoneal carcinoma.

Results

Satisfactory results were achieved in all 115 patients. Median follow-up was 322.0 days. There were no patients who needed a nasogastric tube after PTEG. Seven of 115 patients were able to free from tube feeding due to PTEG tube feeding support. About the complications, there was 1 patient with severe bleeding requiring blood transfusion, one patient had tracheal penetration, which was managed conservatively. Other complications were minor oozing bleeding in seven patients that did not require blood transfusion, subcutaneous emphysema in two patients, which were managed conservatively. Complication rate was 10.4%. No patient required surgical treatment or died after PTEG.

Conclusion

PTEG is feasible, safe, and useful　for long-term nutrition for the patient who is contraindicated to PEG. PTEG may become the only procedure of the liberation from nasogastric tube for the patient who is contraindicated to PEG PTEG is the ideal solution for the patients with PEG contraindicated in the tube feeding.

Disclosure

Nothing to disclose

Introduction

Immunomodulators and biologicals play an essential role in current IBD management, but are associated with increased risk of infections. In light of the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. However, mild and moderate infections take longer to clear in immunosuppressed patients, have been reported to be the most burdensome adverse drug reaction according to patients, and can negatively influence drug adherence.

Aims & Methods

Aim: To assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.
Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. [1] The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients and using the PRIQ which was implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for infections.

Results

In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female, mean age at cohort entry 48.3 years [SD 14.8], mean disease duration 12.4 years [SD 10.8]) were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up. This resulted in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively. Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections types, respectively (Table 1). Compared to patients without treatment, patients on immunosuppressive treatment more frequently experienced infections of any severity (mild vs. no treatment: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p<0.001, moderate vs. no treatment: IRR 1.42 [95%CI 1.20-1.69] p<0.001). On multivariable logistic regression, female sex (mild adjusted odds ratio [aOR] 1.96 [95%CI 1.38-2.79]; moderate aOR 1.71 [95%CI 1.15-2.54]), smoking status (mild aOR 1.66 [95%CI 1.15-2.41]; moderate aOR 1.86 [95%CI 1.05-3.28]), higher BMI (moderate aOR 1.05 [95%CI 1.02-2.00]), and more comorbidities (mild aOR 2.41 [95%CI 1.46-3.98]; moderate aOR 1.82 [95%CI 1.07-3.11]) were all significantly associated with the development of mild and moderate infections.

Conclusion

​In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

References

[1] Rezazadeh Ardabili A, van Esser D, Wintjens D, et al. Development and validation of a remote monitoring tool for assessment of mild, moderate, and severe infections in Inflammatory Bowel Disease [published online ahead of print, 2023 Feb 16]. J Crohns Colitis. 2023;jjad023. doi:10.1093/ecco-jcc/jjad023

Disclosure

M.P. reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZonMw (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. D.J. reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. Z.M. reports grants form MLDS, Niels Stensen Fellowship and Galapagos. A.v.B. has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from Pfizer, TEVA, Eurostars funding, ZonMw, all outside the submitted work.
The other authors have nothing to disclose relevant to this publication.