bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1038 Does combination immunomodulator therapy impact real-world biologic effectiveness in Inflammatory Bowel Diseases?A propensity score analysis in patients treated with anti-TNF and non-anti-TNF biologics in the UK IBD BioResource
Authors: Desoki R , Kapizioni C , Lam D , Balendran K , Al-Sulais E , Subramanian S , Pele L , Parkes M , Raine T 
Published: January 2024

Abstract

Background
Randomised controlled trials have demonstrated that the combination of infliximab and azathioprine is superior to either drug as monotherapy both in patients with Crohn’s Disease (CD) and ulcerative colitis (UC). Data on the combination of other biological agents -including other anti-TNFs, vedolizumab and ustekinumab- and immunomodulators (IMMs) is lacking or shows conflicting results. Given the risks of combination therapy, physicians are often hesitant on whether to combine IMMs with biologic therapies.

Methods
We measured the effectivenessof biologic therapies [infliximab (IFX), adalimumab (ADA), golimumab (GLM), vedolizumab (VDZ) and ustekinumab (UST)] in patients with UC and CD with and without IMM use enrolled in the UK Inflammatory Bowel Disease (IBD) BioResource over long durations of followup.Demographic, disease, treatment and outcome data were retrieved. Inverse probability of treatment weighting (IPTW) was used to balance groups of those receiving vs those not receiving IMM using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. Effectiveness of treatment was based on persistence free of treatment discontinuation or treatment failure. Failure was defined as occurring if any of the following occurred: (a) clinician-recorded treatment failure (b) start of treatment with a different advanced therapy (c) occurrence of resectional or defunctioning bowel surgery. We compared Kaplan Meier curves for treatment failure-free survival after IPTW and used a log rank test for differences between the groups.

Results
In UC, we included 2479 patients receiving IFX (1173 on IMM), 1117 ADA (401 on IMM), 188 GLM (77 on IMM) and 1256 VDZ (392 on IMM). In CD, we included 5956 patients receiving IFX (3062 on IMM), 4524 ADA (1898 on IMM), 1067 VDZ (340 on IMM) and 627 UST (198 on IMM).As expected, combination IMM therapy was associated with increased drug effectiveness for IFX in both UC and CD. Combination IMM therapy was also associated with increased effectiveness of ADA in CD. For all other drugs, there was no significant benefit for combination IMM. Hazard ratios(HRs) for the effect of IMM of each drug effectiveness in UC and CD are summarised (Figure 1).

Conclusion
We confirm prior results indicated that IFX effectiveness is improved by concomitant use of an IMM in both UC and CD.In contrast to RCT data but in accordance to other robust real-world studies, we find evidence that for ADA in CD concomitant IMM can increase drug effectiveness. We find no evidence of benefit for concomitant IMM for other biologics in UC or CD.
P1074 Impact of body mass index (BMI) on clinical outcomes and drug levels in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study
Authors: Yarur A , Hanauer S B , Schreiber S , Colombel J F , Deepak P , Jeong A L , Kim D H , Lee Y N , Danese S 
Published: January 2024

Abstract

Background
Obesity and high levels of visceral adipose tissue are associated with lower response rates to intravenous (IV) infliximab (IFX).1 Subcutaneous (SC) IFX is a novel formulation that demonstrated superiority to placebo as maintenance therapy in patients (pts) with moderate-to-severe active Crohn’s disease (CD) in the Phase 3 LIBERTY-CD study. Assessing efficacy of SC IFX by BMI is important as, unlike the IV formulation, pts receive a fixed dose. This post hoc analysis aimed to assess the association between BMI and the efficacy of SC IFX therapy.

Methods
Data from LIBERTY-CD (NCT03945019) were analysed; 231 pts from the SC IFX arm were divided into four subsets by their BMI: underweight (BMI &lt;18.5 kg/m2, n=27); normal (18.5–24.9 kg/m2, n=133); overweight (25–29.9 kg/m2, n=53); obese (≥30 kg/m2, n=18). Co-primary endpoints at Week (W) 54 (clinical remission [CD Activity Index (CDAI) score &lt;150]; endoscopic response [≥50% decrease in Simple Endoscopic Score for CD (SES-CD) from baseline (BL)]) and W54 change from BL in CDAI score were assessed by BMI subset. Correlations between BMI and CDAI score, SES-CD or median trough level of infliximab (TLI), and the impact of BMI on W54 TLI, were evaluated. Analyses were conducted in a descriptive manner.

Results
At W54, there were no statistically significant differences in co-primary endpoints or change from BL in CDAI score across BMI subsets, despite descending trends in rates of achieving co-primary endpoints, change in CDAI score and TLI with increasing BMI (Table). From the underweight to obese subsets, clinical remission rates were 63.0%, 66.2%, 58.5% and 44.4% (p=0.125), endoscopic response rates were 55.6%, 36.1%, 41.5% and 27.8% (p=0.207) and median changes from BL in CDAI score were −227.3, −212.9, −196.2 and −204.5 (p=0.358). No significant correlations were observed between BMI and CDAI score (Pearson r=0.0972/p=0.141; Spearman rank r=0.0619/p=0.349) or BMI and SES-CD (Pearson r=0.0446/p=0.507; Spearman rank r=0.0375/p=0.577), while there was a weak, but significant, negative correlation between BMI and TLI (Pearson r=−0.2808/p&lt;0.001; Spearman rank r=−0.2829/p&lt;0.001) (Figure). Additionally, there was a significant difference in median W54 TLI across BMI subsets from underweight to obese (17.0, 13.6, 9.3 and 6.6 µg/mL; p=0.007) (Table).

Conclusion
While there was a significant difference in TLI across BMI subsets, there was no statistically significant impact of BMI on W54 clinical or endoscopic outcomes. These results could be explained by the relatively high TLI achieved with the SC formulation. Further larger and longer-term studies including pts with morbid obesity and utilising body composition assessment are warranted.
1Yarur A et al. Gastroenterology 2023;165:963–75.
P1104 Shifting Surgical Landscape in Crohn's Colitis: Laparoscopic Supremacy and Robotic Upsurge
Authors: Violante T , Ferrari D , Novelli M , Larson D 
Published: January 2024

Abstract

Background
Crohn's disease (CD) is a chronic inflammatory bowel disorder that can cause transmural inflammation throughout the digestive tract. When CD affects the colon, it is known as Crohn's colitis (CC), a serious condition often requiring surgical resection. Surgical trends in CC have changed significantly over the past decade, shifting towards minimally invasive surgery, with laparoscopic and robotic procedures becoming increasingly common. This study examines how surgical trends in CC have changed in recent years and predicts how they may change.

Methods
We conducted a retrospective analysis using the ACS-NSQIP database, focusing on patients who underwent colonic resections for CC between 2012 and 2021, including 20,109 patients. Our main goal was to examine trends in open, laparoscopic, hand-assisted, and robotic surgery. We utilized time series analysis, specifically quarter and year of admission data, and employed Vector Autoregressive (VAR) models to explore the dynamic relationships among these surgical techniques. To analyze the time trends, we reported the quarter (Q) and year of admission. These models enabled us to forecast future trends, accompanied by 95% confidence intervals, extending our predictions up until Q2 of 2025.

Results
As shown in Figure 1, open surgery has been the most common approach to CC since Q1 2012, accounting for 52.3% of all procedures. Laparoscopic surgery was the next most common approach, at 33.3%, followed by hand-assisted laparoscopy at 14.4%. Laparoscopy rapidly expressed market supremacy, by steadily becoming the most widespread approach by Q2 of 2017, representing 42.2% of CC surgery and peaking in Q2 2020 at 43.5%. This growth in laparoscopy came at the expense of open surgery, which experienced a significant decline, reaching its lowest point of 28.5% in Q2 2021. Hand-assisted procedures gradually increased in popularity over the years but remained less popular than open and laparoscopic methods, peaking at 24.0% in Q4 2019. Robotic procedures experienced slow but steady growth, from 1.9% in Q1 2013 to 10% in Q2 2021.
Future trends suggest that laparoscopy will continue to grow steadily, reaching 45% (95% CI 28.2-61.7%) by the end of our prediction period. Robotic surgery is poised to significantly shift CC surgery trends, with resections expected to reach 12.6% (95% CI 9.3-15.8%) by Q2 2025, while a subsequent decline in open procedures to 20.8% (95% CI 0-43%).

Conclusion
Laparoscopic surgery has emerged as the favored surgical approach in CC and is expected to maintain its supremacy into the near future. Open colonic resections are anticipated to decline, making way for the increasing prevalence of robotic surgery.
P1110 Collagenous colitis, clinical features, risk factors and treatment outcome: A large case series from the largest teaching Hospital in London, UK
Authors: Kottwitz J , mudege T , Giaslakiotis K , Hoque PhD S S 
Published: January 2024

Abstract

Background
Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from macroscopically normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Here, we looked at, risk factors and treatment outcome of collagenous colitis in large series of cases.

Methods
In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed.

Results
In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. PPI uses were associated with in 81% cases. While NSAIDS and statin were associated in 56% and 49% cases respectively. We also found that SSRI use were noted about 31% cases.
Painless watery diarrhoea was the main cause for referral in 90% of cases, while complaint of abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Forty-eight (48%) patients received treatment with Budesonide, 46% treated with loperamide, 5% with Immunomodulator or Biologics and 1% Bismuth Subsalicylates respectively. Other autoimmune disease were associated in 6% cases and 2% cases were associated with Coeliac disease. in Nineteen (19%) of cases symptoms improved immediately after stopping above associated drugs without any specific therapy.
Twenty-five (25%) percent relapses 6 months after stopping of therapy. Patients present with abdominal pain, and arthralgia were significantly (p&lt;0.001) higher risk of relapsing compared to patients with other symptoms.

Conclusion
In this large series of collagenous colitis, we found that in addition to associated drug use is not only risk, patient presents with abdominal pain and arthralgia have higher risk of relapse, after stopping of therapy of collagenous colitis . Further studies are needed to identify biomarker of this frustrating disease which has significant impact on patients of quality of life.
P1111 Prevalence and risk factors for active tuberculosis in Tunisian IBD patients
Authors: Ben Safta N , Hlila T , Ben Mustpha N , Laabidi S , Gouiaa D , Serghini M , Fekih M , Labidi A , Boubaker J 
Published: January 2024

Abstract

Background
IBD patients are at risk of active tuberculosis,given the use of immunosuppressive treatments.Our country is an endemic region for tuberculosis,which may increase this risk.
The aim of our study was to estimate the prevalence of active tuberculosis in IBD patients with prior screening and to investigate associated risk factors.

Methods
This was a retrospective and descriptive study,including all IBD patients admitted in the department,who had a screening for latent tuberculosis,over a 10-year period[2012-2022].Patients with less than 12 months' follow-up were excluded.

Results
We included 100 patients, 52 men and 48 women.Crohn's disease(CD)was present in 86% of cases,and ulcerative colitis in 14%.CD was predominantly ileocolic (47%).The phenotype of luminal CD was inflammatory, stenosing and fistulizing in 36.6%,28% and 35.4% of cases respectively.Anoperineal involvement was present in 41.9% of CD patients.At the time of screening, patients were on salicylates, steroids and thiopurines in 13%,27% and 22% of cases respectively.Body mass index median was 22.7kg/m².Two-thirds of patients(65%)were in a flare-up at the time of screening,with 50.8% in moderate severity, and 3.1% in severe acute colitis.Ninety patients had a negative TST.The quantiFERON test was positive in 9 patients and indeterminate in one,in four of them, the TST was also positive. There were no abnormalities on chest X-rays in all patients.Fifteen patients received chemoprophylaxis, mainly because of suspected latent tuberculosis, but also because of severe undernutrition despite a negative workup in 3 patients.Chemoprophylaxis was isoniazid monotherapy for 9 months,except for 3 patients who received isoniazid and rifampicin dual therapy for 3 months.The prevalence of active tuberculosis in our patients was 11%.The median time from onset of tuberculosis to screening was 12 months.Almost all patients were on anti-TNFα monotherapy(n=4) or combotherapy(n=6).One patient was on azathioprine only. Chest CT scans showed signs suggestive of tuberculosis in only 2 patients.Among patients who developed active tuberculosis, 2 had previously received chemoprophylaxis for a positive TST. In a univariate study,we analyzed all variables for risk factors associated with the occurrence of tuberculosis in our patients.Apart from the use of anti-TNF drugs(p=0.03),no statistically significant associations were found:severity of relapse during screening(p=0.3),undernutrition as evidenced by a low BMI(p=0.92),albuminemia(p=0.77),C reactive protein(p=0.8).

Conclusion
The median delay to onset of active tuberculosis suggests post-screening transmission.This is further evidence of the need to shorten the time required for systematic updating of the tuberculosis work-up in endemic countries.
P1139 Lymphocytic Colitis: A large case series in the United Kingdom
Authors: Gilmour N , Giaslakiotis K , Hoque S 
Published: January 2024

Abstract

Background
Lymphocytic colitis, a type of microscopic colitis, was previously thought to be a rare condition. It is a histological diagnosis characterised by chronic loose stools and normal findings on endoscopy. It is now thought that it could be implicated in up to 10% of people with chronic diarrhoea, and has traditionally been associated with certain medications. We conducted a retrospective case analysis of patients diagnosed with the condition on histology between January 2018 till December 2022.

Methods
A list of patients who had undergone colonoscopy and biopsy for chronic diarrhoea, with no evidence of inflammatory bowel Disease (IBD), was generated. The patient’s electronic health records were then manually analysed, and data was collected using certain parameters including presence of autoimmune disease, faecal calprotectin levels/QFIT, smoking status, medication use (NSAIDS, PPI, Statins or SSRIs), colonoscopy findings, treatment choice and treatment outcomes. 121 patients were eligible based on histopathology consistent with a diagnosis of lymphocytic colitis.

Results
The median age was 63, with a 3:2 split of female to male patients. 63% reported painless, chronic diarrhoea lasting more than 6 weeks. 10.7% had painless and bloody diarrhoea, 23% had diarrhoea with abdominal pain. 25.4% had evidence of autoimmune disease. 43% were taking a PPI, 6.6% and NSAID, 41% a statin and 25.6% an SSRI. 27% were active smokers at the time of presentation. 62.8% of patients had a normal colonoscopy report, with the rest having ‘’abnormal reports” due to polyps. Faecal calprotectin levels ranged from 20-954. QFIT was positive in 35% of patients. 34% of patients were treated under a gastroenterologist. Of those who received budesonide only: 46% recovered with no relapse, 20% had relapsed in under 6 months, 16% relapsed after 6 months, 16% did not present again. Of the patients who received loperamide only, 66% reported resolution of symptoms. All histology demonstrated lymphocytosis in the lamina propria, 16% had expansion of the subepithelial collagen band, often termed ‘incomplete Microscopic colitis’.

Conclusion
Use of PPIs, statins and SSRIs are highly represented in the data, compared with general population usage. Treatment with either budesonide or loperamide generally lead to better symptom control, indicating patients should be referred to gastroenterology upon diagnosis. Clinicians should judiciously prescribe the above medications with clear indication and avoid prescribing indefinitely.
P1143 Per- and poly-fluoroalkyl substances (PFAS) exposure is associated with later occurrence of inflammatory bowel disease
Authors: Agrawal M , Midya V , Maroli A , Valvi D , Magee J , Ungaro R , Porter C , Petrick L , Colombel J F 
Published: January 2024

Abstract

Background
Environmental chemical exposures are increasingly acknowledged as risk factors for inflammatory bowel disease (IBD). Per- and poly-fluoroalkyl substances (PFAS), a large class of persistent fluorinated organic chemicals, widely used in the modern environment, may be implicated in IBD etiology, but data are conflicting.

Methods
We investigated the association of PFAS mixture concentrations in pre-diagnostic serum with adult-onset IBD in a pilot study within the pre-clinical Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study. This is a nested case-control study of military personnel with Crohn’s disease (CD), ulcerative colitis (UC), and age-, sex-, and race-matched healthy controls with serum samples obtained at four-time points 1-10 years prior to IBD diagnosis. Using untargeted liquid-chromatography high-resolution mass spectrometry analytical approach, we conducted an untargeted metabolomic analysis and semiquantitative measurement of fluorinated compounds, including legacy PFAS and emerging PFAS chemicals. We used weighted quantile sum regression models adjusted for confounders to study the association of PFAS as a mixture with the odds of CD and UC at each time point.

Results
Our study sample included individuals with CD, UC, and matched healthy controls (n=25, each group, 4 samples per individual). Baseline characteristics were similar across cases and controls. We identified nine well known PFAS compounds and 27 other known fluorinated compounds. The chemical mixture of fluorinated compounds, including the known PFAS, in the serum samples within one year of diagnosis was associated with higher odds of CD and UC [odds ratio (OR) 2.13, 95% CI 1.33, 3.41, and 1.76, 95% CI 1.15, 2.68, respectively] per one unit increase in decile. These associations remained consistent for the PFAS mixture measured in serum at all four time points up to 10 years prior to diagnosis for both CD and UC (Figure). Major contributors to the overall mixture indices included legacy PFAS, as well as emerging PFAS chemicals.

Conclusion
We observed a substantial increase in the odds of CD and UC among individuals with higher serum PFAS mixture levels up to 10 years prior to diagnosis. Studies to understand underlying mechanisms are ongoing.
P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel disease
Authors: Martinez Lozano H , Saralegui Gonzalez P , Fueyo Peláez P R , García García A , Miranda-Bautista J , Reigadas Ramírez E , Alcalá Hernández L , Muñoz García P , Marín-Jiménez I , Menchén L 
Published: January 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases).

Methods
We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis.

Results
Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p&lt;0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P&lt;0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P&lt;0.001) were associated with a higher risk of CDI.

Conclusion
The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.