bluuebunny/crossref_metadata_2025 huggingface dataset:
P948 Hand Grip Strength is a useful objective measure associated with fatigue and impaired quality of life in patients with inflammatory bowel disease
Authors: Stack R , Ní Chonnacháin C , Doherty J , O'Moran N , Girod P , Noronha N , Gibney E R , Doherty G A
Published: January 2024

Background

Hand grip strength (HGS) is a recognised tool for diagnosis / screening of muscle impairment and sarcopenia, however it remains underutilised in IBD cohorts. The aim of the study was to measure the prevalence of muscle impairment by HGS and association with quality of life in a cohort of UC patients in disease remission.

Methods

Potential subjects were prospectively identified for selection from the Gastroenterology Department in St. Vincent’s University Hospital Outpatient Department. All patients had a confirmed diagnosis of UC for >3 month with stable, quiescent disease (no escalation of medical therapy in the previous 3 months with a documented Faecal Calprotectin (FCP) <100 μg/g). Along with anthropometry data, HGS measurements were performed using the Jamar®Plus+Dynamometer. Quality of life scores were measured using 36-item Short Form Survey (SF-36), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Short Health Scale questionnaires were measured. Linear regression was used to calculate standardised β-coefficients for correlation analysis. Non-parametric data was analysed using algorithms including Kruskal-Wallis and Wilcoxon rank-sum test.

Results

60% (n=18) of subjects had a HGS outside the lower limit of the 95% confidence interval of age and sex matched normative values, indicative of impaired grip strength. This was significantly more prevalent in subjects with normal BMI than BMI>30 (p=0.035). Prevalence of fatigue was 43.3% according to SIBDQ question 2a and ’Energy/Fatigue’ scores of SF-36 were significantly lower compared to normal Irish population data (51.0 v 64.8, p = 0.0002). Composite scores of fatigue in both SIBDQ (question 2a) and SF-36 were compared, resulting in a standardized β-coefficient of 0.52 of statistical significance (p value = 0.003).Significant correlation was demonstrated between predicted HGS and ’Energy/Fatigue’ SF-36 scores (standardised β-coefficient = 0.4, p value = 0.027).

Conclusion

HGS is a convenient means of measuring muscle function in an IBD population and correlates significantly with ’Energy/fatigue’ SF-36 scores. These results suggest sarcopenia as a potentially important contributor to fatigue in patients with IBD and suggest HGS is an objective, easily applied objective measure which merits validation as an outcome measure for intervention studies to improve fatigue in patients with IBD.
P966 The intra-patient variability of adalimumab clearance during an intensive sampling study of Crohn’s disease patients receiving maintenance therapy
Authors: Strong A , Aragon-Han P , Sparrow M , Dervieux T , Ward M
Published: January 2024

Background

Lower adalimumab (ADA) clearance (CL) is associated with improved outcomes in Crohn’s disease (CD) and may be a superior pharmacokinetic (PK) measure than ADA concentrations. We compared intra-patient variability in ADA CL and concentrations within a 14-day treatment cycle and across two consecutive cycles under maintenance treatment.

Methods

In a previous PK study of CD patients receiving maintenance ADA 40mg fortnightly, samples were collected intensively at 3 visits (day 4-6, 7-9, and 13-14 post dose) across 2 consecutive cycles. Available sera from this cohort were subsequently used to measure ADA concentrations (lower limit quantification: <1.6 µg/mL) and antibody to adalimumab (ATA) status using a drug tolerant homogeneous mobility shift assay, and albumin. Apparent ADA CL (L/day) was calculated incorporating these measure parameters in a nonlinear mixed effect model with Bayesian priors (under steady state assumption) with dose and inter-dose interval with ATA and albumin as covariate. Rates of sustained clinical and biochemical remission (Harvey Bradshaw Index (HBI) score consistently <5 and CRP levels consistently <3 mg/L) were estimated for each patient. Longitudinal changes in PK parameters within-and-across cycles were evaluated using intra-patient coefficient of variation and linear mixed effect models.

Results

Sera was available from 70 study visits in 12 patients (6 males, mean age 36 years). Median ADA concentrations and CL were 8 µg/mL (IQR 6.0-10.4) and 0.374 L/day (IQR 0.29-0.43), respectively, with ATA detected in one patient (#9). Estimated ADA concentrations and CL is presented in the Table. Intra-patient variability in CL was much lower across the two 14-day cycle (9% and 7%, respectively) compared to intra-patient variability in ADA concentration (15% and 13%, respectively). Linear mixed effect models confirmed these findings with no impact of sampling time on CL (intercept=0.46±0.12 L/day; slope estimate=0.002±0.002 L/day; p=0.16) as compared to significant change in ADA concentrations (intercept=10.6±1.2 µg/mL; slope estimate=-0.25±0.03 µg/mL; p<0.01) over inter-dose interval sampling time. Sustained clinical and biochemical remission was achieved in 5/12 patients (42%); none presented with CL >0.8 L/day (a cut-off previously associated with worse outcomes). Of 7 patients without sustained clinical and biochemical remission, two presented with optimal concentrations (> 10 µg/mL), thus suggestive of mechanistic failure, and one developed ATA, lower concentration and higher ADA CL.

Conclusion

CL is subject to less intra-patient variability than ADA concentrations, supporting its assessment at any time point within a 14-day treatment cycle.
P1011 Methotrexate polyglutamates in paediatric inflammatory bowel disease: Novel tool for therapeutic drug monitoring?
Authors: Vermeer E , Struys E A , van Limbergen J E , de Boer N K , de Jonge R , de Meij T G J
Published: January 2024

Background

Methotrexate (MTX) is increasingly prescribed in paediatric inflammatory bowel disease (IBD), but therapeutic drug monitoring (TDM) is currently not feasible due to its characteristic pharmacokinetics and short half-life in plasma, which amounts to approximately 2.5-6.5 hours. Because of this, plasma MTX is no longer detectable shortly after administration. However, MTX-polyglutamates (PG1-5) are formed intracellularly and accumulate over time. Recently, we developed a technique for targeted erythrocyte MTX-PG analysis with the potential for TDM. Data in paediatric IBD with this technique are lacking so far. Here, we aimed to identify the potential of erythrocyte MTX-PG analysis to measure MTX levels in paediatric IBD.

Methods

In this observational cross-sectional study, we determined MTX-PG concentrations in erythrocytes retrieved from blood samples of paediatric IBD patients on low-dose MTX maintenance therapy, defined as exposure to a stable dose of MTX for at least twelve consecutive weeks. MTX-PG concentrations were determined by stable-isotope dilution liquid chromatography mass-spectrometry. Furthermore, we evaluated the effects of route of administration (oral versus subcutaneous), MTX dosage, and anthropometric data on MTX-PG concentrations.

Results

Fifty-two paediatric IBD patients on MTX maintenance therapy were included. The predominant subspecies was MTX-PG3 (mean 30.5 nmol/L, SD ± 20.0) and the mean MTX-PGtotal concentration was 88.6 nmol/L (SD ± 52.6). A higher dose was linearly associated with significantly higher MTX-PG3 (r = 0.56), MTX-PG4 (r = 0.52), MTX-PG5 (r = 0.48) and MTX-PGtotal (r = 0.49) levels. When adjusted for body surface area, MTX dose was also linearly associated with significantly higher MTX-PG3 (r = 0.51), MTX-PG4 (r= 0.39), and MTX-PGtotal (r= 0.40) concentrations. A reliable comparison regarding route of administration was not possible in this cohort, due to the small number of patients receiving subcutaneous MTX (n=3).

Conclusion

We observed high inter-individual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, effectivity and toxicity.
P1027 Optimizing IBD Medication and Therapy: An Interdisciplinary University Outpatient Approach
Authors: Binder B , Elger T , Huss M , Loibl J , Tews H C , Kandulski A , Kratzer A , Müller M , Fleischmann D
Published: January 2024

Background

A large proportion of patients with chronic inflammatory bowel disease (IBD) take a wide range of different medications, which harbor a potential risk of pharmaceutical (pharm.) interactions. Furthermore, these patients frequently seek professional advice regarding additional medications or alternative treatment options. In this study, an interdisciplinary medical-pharmaceutical team conducted a standardized survey and a pharmaceutical medication check in an IBD outpatient department. The aim was to evaluate and enhance individual therapy adherence and medication safety.

Methods

Prior to the appointment, patients were requested to provide their current medication list and to complete a standardized questionnaire regarding their general compliance and any unmet questions or concerns about their IBD therapy. A clinical pharmacist analyzed the questionnaire and carried out a thorough assessment of the list of medications for possible interactions and the potential for improvement. One day before the patient`s appointment, the pharmacist presented his findings to the treating physician, and possible interactions were discussed. After the appointment, patients were asked to complete a second questionnaire regarding their experience and possible changes in therapy, as well as their previous concerns or responses.

Results

The data from Questionnaire 1 showed two main results: (I) Overall adherence to therapy was found to be sufficiently high, as most patients reported taking their medication regularly and being aware of the main principles of their therapy. (II) Many patients expressed concerns about possible long-term side effects of their therapy and indicated that they needed additional information about their medication (Figure 1A).

Concerning the provided medication plan, 77% of all participants took more than 5 drugs and in 94% of the cases, no previous medication check had been performed. The involved clinical pharmacists suggested 1.3 interventions per patient and in 50% of all cases, at least one medication was discontinued or newly started (Table 1). In the follow-up survey, most patients stated that the interdisciplinary medical counseling had improved both their knowledge and their sense of security of their IBD treatment (Figure 1B).

Conclusion

The interdisciplinary review and monitoring of the current therapy and the individual medication of IBD patients increased patient-specific compliance and medication safety and should therefore be intensified in the future.
P1043 Immunomodulator and advanced therapies for prevention of clinical relapse and loss of response during maintenance phase in Crohn’s disease: A systematic review and network meta-analysis
Authors: Sinopoulou V , Gordon M , Vuyyuru S , Darie A M , Pavlidis P , Moran G
Published: January 2024

Background

Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Given lack of adequate head-to head clinical trials it is challenging to position these therapies in the management algorithm. Therefore we performed this network meta-analysis to inform therapeutic decisions.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse (loss of clinical remission), loss of clinical response, adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects meta-analysis and network meta-analysis (using a frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results

A total of 32 RCTs comprising 10,924 patients were included in the analysis. On network meta-analysis of 15 interventions based on prevention of clinical relapse, combination of infliximab (IFX) and azathioprine (AZA) (RR 0.31, 95%CI [0.17-0.56]), IFX (RR 0.62, 95%CI [0.5-0.76], moderate certainty), and adalimumab (RR 0.68, 95%CI [0.55-0.84], moderate certainty) were the only agents that were effective compared to placebo (Figure 1). Methotrexate (RR 0.57, 95%CI [0.32-1.03], low certainty) and azathioprine (RR 0.82, 95%CI [0.62-1.1]), very low certainty) were not effective. On analysis based on prevention of clinical response for nine interventions, there was high certainty evidence for ustekinumab (RR 0.73, 95%CI [0.61-0.86]), upadacitinib (RR 0.64, 95%CI [0.57-0.72]), and moderate certainty of evidence for infliximab (RR 0.71, 95%CI [0.59-0.84]), adalimumab (RR 0.68, 95%CI [0.61-0.75]), certolizumab (RR 0.57, 95%CI [0.47-0.7]), CTP13 (RR 0.46, 95%CI [0.38-0.57]), vedolizumab (RR 0.82, 95%CI [0.68-0.99]), natalizumab (RR 0.54, 95%CI [0.43-0.68]). Tofacitinib was not effective and there was no data available for immunomodulators and combination therapies for this outcome. On analysis of serious adverse events advanced therapies were of no difference to placebo (very low certainty).

Conclusion

On network meta-analysis immunomodulators and advanced therapies for maintenance phase, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for prevention of clinical relapse. There was moderate to high certainty evidence to suggest newer advanced therapies are effective in prevention of loss of clinical response.
P1058 Safety and effectiveness of subcutaneous infliximab formulation in difficult-to-treat Crohn’s Disease patients with previous exposure to intravenous infliximab: A case-series
Authors: Mulinacci G , Pirola L , Piazza O Sed N , Laffusa A , Fichera M , Massironi S , Invernizzi P , Caprioli F A , Viganò C
Published: January 2024

Background

Despite the increased therapeutic armamentarium for Crohn’s Disease (CD), a relevant proportion of patients fail to respond to multiple therapies and ultimately require surgery. Intravenous (IV) infliximab (IFX) reinduction after a drug holiday is associated with reduced drug efficacy and both acute and delayed infusion reactions, due to immunological mechanisms and development of antidrug antibodies, and is currently contraindicated. Recently, a subcutaneous (SC) formulation of IFX has been developed, demonstrating equal efficacy and safety with a better immunogenicity profile (i.e. biobetter). This study evaluated the safety and effectiveness of retreatment with SC IFX in CD patients previously exposed to IV IFX.

Methods

Data were retrospectively collected through the Electronic Medical Record. Patients included were IV IFX-experienced and subsequently treated with SC formulation after a period of drug holiday ≥ 1 year. Collected data included demographics, disease characteristics and activity, current and previous treatment, adverse events, and reasons for previous anti-TNFα discontinuation.

Results

12 patients with CD were included. Mean age at diagnosis and disease duration were 16.2 (±6.7 SD) and 15.6 years (±7.4 SD) respectively. All patients had failed at least three biologics, and 7 patients underwent previous surgery. The main reason for IV IFX discontinuation was secondary failure (4 patients, 33%). Median time from IV suspension to SC treatment start was 106.5 months (IQR=98.5) with median treatment duration of 24 (IQR=37.5) and 7.5 (IQR=4.5) months for IV and SC IFX respectively. SC IFX was introduced as an add-on dual biologic therapy in 5 patients (3 treated with Ustekinumab, 2 with Vedolizumab).

Overall, one adverse event with SC IFX was reported: a grade 2 serum sickness reaction, which led to treatment discontinuation. No immediate allergic reactions were reported. 10 patients had at least 6 months of follow-up. Median HBI reduction at 6 months from SC IFX begin was significant (p<0.05), varying from 7.5 (IQR=3.5) to 3.5 (IQR=4).

C-Reactive Protein levels normalized in 3 (38%) patients, reduced in 2 (25%), and remained stable in 3 (38%). Faecal calprotectin normalized in 2 (29%) patients, reduced in 1 (14%), remained stable in 2 (29%), and increased in 2 (29%). At 6 months steroid free remission rate (HBI≤4) was 66%.

Conclusion

This is the first report showing that SC IFX reinduction in CD patients previously exposed to IV IFX is safe, even after a long drug holiday. It might be regarded as a rescue option in difficult-to-treat patients, either alone or combined with other immunosuppressants.
P1071 Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID
Authors: Caron B , Seksik P , Buisson A , Wils P , Savoye G , Stefanescu C , Laharie D , Guillo L , Abitbol V , Bonnet J , Altwegg R , Vuitton L , Moussata D , Bourreille A , Biron A , Gilletta C , Fumery M , Nahon S , Nancey S , Camara H , Peyrin-Biroulet L
Published: January 2024

Background

Several adalimumab preparations are now available on the market for patients with inflammatory bowel disease. Comparative satisfaction and tolerability are unknown. The aim of this study was to investigate inflammatory bowel disease patient satisfaction with approved adalimumab biosimilars and their originator.

Methods

In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with inflammatory bowel disease across 45 centres affiliated with the GETAID who completed a satisfaction questionnaire comprising four items each rated by a 10 points-scale. The differences in responses were performed using one-way analysis of variance followed by Tukey's Honest Significant Difference test.

Results

The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%), and Hulio® (105/941, 11.2%). Mean overall satisfaction rate with adalimumab was 8.5 [standard deviation 1.8]. Overall satisfaction was significantly higher in patients treated with Humira® (8.6 [1.5]), Hulio® (8.6 [1.8]) or Amgevita® (8.5 [1.4]) (p<0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 [1.4]), Humira® (8.9 [1.3]) and Hulio® (8.9 [1.7]) (p<0.05). A total of 299 patients (31.8%) described injection site reactions. Two hundred twenty-three patients (23.7%) reported that they were previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects.

Conclusion

In this real-world setting, patients with inflammatory bowel disease had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.
P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative Colitis
Authors: Choon X Y , Patel C , White C , Centritto A , Lal N , Sharma E , Chester D , Dart R , Anderson S , Ray S , Mawdsley J , Irving P , Samaan M
Published: January 2024

Background

Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies.

Methods

We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC<150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events.

Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables.

Results

42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies.

At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4).

At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to <150 μg/g.

Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p<0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p<0.0001, n=19), with 9 (47%) patients achieving histological remission.

6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction.

3 patients (7%) reported facial acne as an adverse event, no others were reported.

Conclusion

Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.
P1081 Pharmacokinetics and immunogenicity of the ustekinumab biosimilar candidate ABP 654 in patients with moderate-to-severe plaque psoriasis
Authors: Chow V , Mytych D T , Blauvelt A , Papp K , Barragan C , Yamauchi P , Crowley J , Franklin J
Published: January 2024

Background

ABP 654 is being developed as a biosimilar candidate to ustekinumab reference product (RP), a biologic agent used in the treatment of certain chronic, immune-mediated, inflammatory diseases. Previously, we reported no clinically meaningful differences in efficacy or safety between ABP 654 and ustekinumab RP in a 52-week randomised, double-blinded, active-controlled study in patients with moderate-to-severe plaque psoriasis. Here, we describe the pharmacokinetics (PK) and anti-drug antibody (ADA) results from the same study.

Methods

A total of 563 patients were randomised in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a subcutaneous dose of 45 mg (baseline body weight [BW] ≤ 100 kg) or 90 mg (baseline BW > 100 kg) (Fig. 1). Serum samples for PK and ADA evaluations were collected at various timepoints. Concentrations of ABP 654 and ustekinumab RP were measured using an electrochemiluminescent (ECL) assay based on the Meso Scale Discovery platform. All ADA samples were tested in a validated binding, acid-dissociation ECL assay. Samples testing positive for binding antibodies were evaluated for neutralising ADA in a validated ECL-based affinity capture elution assay.

Results

From baseline to Week 52, the geometric least-squares (LS) means of trough serum concentrations were similar between the ABP 654 and ustekinumab RP groups. In addition, the geometric LS means of serum concentrations were similar post Week 28 for patients (ABP 654, n=25 and ustekinumab RP, n=34) who received dose intensification. Of patients with a post-baseline ADA result through Week 28, 52 (18.6%) patients in the ABP 654 group and 104 (37.1%) patients in the ustekinumab RP group tested positive for binding ADAs. Of these, 24 (8.6%) patients in the ABP 654 group and 50 (17.9%) patients in the ustekinumab RP group tested positive for neutralising ADAs. For dose intensification patients with a post-baseline result post Week 28, no patients in the ABP 654 group tested positive for binding or neutralising ADAs, and 2 (5.9%) patients in the ustekinumab RP group tested positive for binding and neutralising ADAs.

Conclusion

Throughout the study, serum trough concentrations remained comparable between ABP 654 and ustekinumab RP. While the percentages of binding and neutralising ADAs were numerically lower for the ABP 654 group compared with the ustekinumab RP group through Week 28 (and in patients who received dose intensification), the available clinical efficacy, safety, and PK data suggest that these differences were not clinically impactful. Overall, the results support a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.
P1093 Early life exposure to agriculture and biodiversity influences Crohn’s disease risk in a population-based cohort study
Authors: Agrawal M , Vinkel Hansen A , Colombel J F , Jess T , Allin K
Published: January 2024

Background

Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. Crohn’s disease (CD) clustering has been reported in agricultural areas. However, the role of environmental exposures, particularly in early life, towards IBD risk, has not been systematically evaluated.

Methods

We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and natural vegetation density index during pregnancy and the first two years of life on IBD, CD, and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for the following covariates: sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD.

Results

Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3,768 individuals were diagnosed with IBD. Exposure to the highest and third quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased IBD risk (aHR 1.16, 95% CI 1.02, 1.31 and 1.19, 95% CI 1.07, 1.32, respectively). Conversely, exposure to the highest and third quartiles of biodiversity in early life, compared to the lowest quartile, were associated with a lower IBD risk (aHR 0.90, 95% CI 0.82, 1.00 and 0.90, 95% CI 0.82, 0.99, respectively). These associations were driven by differences in CD risk (Figure), but there was no association with UC risk. Other environmental exposures were not associated with IBD risk.

Conclusion

In a nationwide cohort with long-term follow up data, early life exposure to agriculture land use was associated with an increase in CD risk, while higher biodiversity was protective.
P1105 Short-term exposure to environmental air pollution and inflammatory bowel disease flares: a time-stratified case cross-over study
Authors: Noviello D , Fedrizzi L , Fracas E , Pessarelli T , Conforti F , Pier Mannuccio M , Pesatori A C , Vecchi M , Carugno M , Caprioli F
Published: January 2024

Background

Some epidemiological studies suggest that long-term exposure to environmental air pollutants, such as particulate matter (PM), could have a role in inflammatory bowel disease (IBD) incidence and pathogenesis. However, less is known about the potential effect of short-term air pollution exposure. The aim of this study is to investigate whether short-term exposure to environmental air pollution is associated with the occurrence of IBD flares.

Methods

Anonymized hospital discharge records (HDR) with ICD-9-CM codes 555 (Crohn’s disease) and 556 (ulcerative colitis) for years 2002-2009 from all hospitals of the Lombardy region were collected. All HDR of adult patients (18-75 years) resident in Milan were included, except for recurrent hospitalizations within 6 months. Each record was assigned daily PM ≤10 µm (PM10) concentrations at municipality level by averaging PM10 levels of the day of admission with the levels of the day before (lag01) and of each preceding day up to six days before (lag06). To evaluate the association between PM10 and IBD-related hospitalizations, a time-stratified case-crossover study design was applied. Conditional logistic regression models, calculating Odds Ratios (OR) and 95% Confidence Intervals (95%CI) per increments of 10 µg/m3 of PM10, were performed.

Results

Overall, 2,176 hospital admissions (males=1,137, Crohn’s disease=1,264, ulcerative colitis=912) were included. In the entire population no clear association between PM10 and IBD-related hospitalization was identified, notwithstanding a small risk increase for males (OR: 1.03; 95%CI: 0.99-1.08 at lag04). When further stratifying for ICD code, an increased risk of hospitalization for "left-sided ulcerative colitis" (ICD code: 556.5) was found in males only, for exposures in all days preceding hospitalization up to lag04 (1.28; 1.05-1.28; 59 cases, 207 controls) (Figure 1). In females, the association was weaker, although positive (1.14; 0.91-1.42; 49 cases, 164 controls). No relevant findings emerged when looking at other ICD codes.

Conclusion

We observed an increased risk of IBD-related hospitalization in male patients with left-sided ulcerative colitis per increasing levels of air pollution in the days preceding hospital admission. Although preliminary, our findings suggest the possible role of sex as an effect modifier of the influence that air pollution might exert on IBD flares. Further studies are needed to better comprehend the complex framework characterizing the interplay between environmental and individual factors contributing to IBD.
P1107 Clinical characteristics and prognosis of very young adult-onset Crohn's disease: Results from the Prospective CONNECT Study
Authors: Kim M K , Jung Y , Jang B I , Jung S A , Im J P , Cheon J H , Kim Y S , Kim Y H , Kim J S , Ye B D
Published: January 2024

Background

Although the A2 group according to the Montreal classification accounts for the largest proportion among patients with Crohn’s disease (CD),1 there has been a lack of studies comparing the clinical characteristics and prognosis according to the age at diagnosis within the A2 group.

Methods

We utilised data from the prospective CONNECT study—a nationwide, multicentre cohort study of CD patients in Korea.2 Of 1,175 participants, a total of 945 patients (80.4%) were categorised as Montreal classification of age A2 (≥17 and <40 years at diagnosis). They were further divided into two groups based on the age at diagnosis: very young adult-onset group (≥17 and <20 years, n=275) and young adult-onset group (≥20 and <40 years, n=670).

Results

Isolated ileal diseases were more common in the young adult-onset group (21.5% vs. 30.7%), whilst the frequency of stricturing (B2) or penetrating (B3) behaviours was tended to be lower in the very young adult-onset group than in the young adult-onset group (16.7% vs. 29.7%) (Table 1). Twenty-five patients (9.1%) in the very young adult-onset group underwent intestinal resection compared to 91 patients (13.6%) in the young adult-onset group (p=0.072). The very young adult-onset group had a longer intestinal resection-free survival than the young adult-onset group (p=0.04) (Figure 1a). More patients in the very young adult-onset group received systemic corticosteroids compared with those in the young adult-onset group (62.2% vs. 48.8%, p<0.001) and the corticosteroid-free survival was shorter in the very young adult-onset group compared with the young adult-onset group (p<0.01) (Figure 1b). Complicated behaviors (B2, adjusted hazard ratio [aHR] 4.03, 95% confidence interval [CI] 2.42–6.70, p<0.001; B3, aHR 6.39, 95% CI 4.21–9.72, p<0.001) was independently associated with the risk of intestinal resection.

Conclusion

The very young adult-onset group exhibited distinct disease behaviour at diagnosis and different clinical outcomes compared with the young adult-onset group. Within the A2 group (≥17 and <40 years at diagnosis), the risk of intestinal resection appears to be driven by the intestinal complications.

References

1. Silverberg MS, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19 Suppl A:5A–36A.

2. Hong SW, et al. Clinical features and long-term prognosis of Crohn's disease in Korea: Results from the Prospective CONNECT Study. Gut Liver 2022;16(6):907–920.

Financial support: This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2022ER050400).
P1119 Increased risk of chronic respiratory disease among individuals with Inflammatory Bowel Disease in a prospective cohort study
Authors: Dan L , Xie Y , Fu T , Sun Y , Chen X , Wang X , Wu C , Chen J , Li X
Published: January 2024

Background

Cross-sectional evidence suggests a higher burden of chronic respiratory diseases in people with inflammatory bowel disease (IBD), but there is a lack of prospective evidence to clarify the direction of their associations. This study aimed to investigate the association of IBD with the risk of two major chronic respiratory diseases, chronic obstructive pulmonary disease (COPD) and asthma.

Methods

We included 430,414 participants from UK Biobank and followed them from recruitment (2006-2010) to 2021. COPD and asthma cases were obtained from inpatient data and death register. Using Cox proportional hazards models, we estimated the multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) of developing COPD and asthma in participants with IBD compared with IBD-free groups. We also investigated the association among Crohn's disease (CD) and ulcerative colitis (UC) with the risk of COPD and asthma.

Results

Over a median follow-up of 143 months, there were 11,196 incident COPD and 9831 asthma cases. The adjusted HRs of developing COPD (HR=1.54, 95% CI: 1.33-1.79) and asthma (HR=1.52, 95% CI: 1.29-1.79) were higher for those with IBD when compared with IBD-free participants. Participants with CD and UC were also found to have a higher risk of COPD (CD: HR=1.71; 95% CI: 1.36-2.15; UC: HR=1.45; 95% CI: 1.20-1.75) and asthma (CD: HR=1.73; 95%CI: 1.33-2.25; UC: HR=1.41; 95%CI: 1.15-1.73) when compared with those free of IBD (Table 1).

Conclusion

This study suggested that individuals with IBD have a higher risk of developing COPD and asthma, highlighting the importance of preventing chronic respiratory diseases among IBD patients.
P1124 Nutritional assessment and validation of GLIM Criteria in Inflammatory Bowel Disease patients
Authors: Belén Galipienso O , Bernabeu P , Amrani R , van-der Hofstadt C , Abad A , Cameo J I , Madero L , Gutiérrez A , García del Castillo G , García Sepulcre M F , Zapater P , Bernal L , Moreno V , Jover R , Sempere R
Published: January 2024

Background

There is currently no validated method of assessing nutritional status in non-hospitalised patients with inflammatory bowel disease (IBD). The Global Leadership Initiative on Malnutrition (GLIM) has developed criteria for malnutrition including phenotypic criteria (low BMI, and reduced fat-free mass index (FFM)) and etiologic criteria: reduced food intake or malabsorption and chronic inflammation. In the GLIM algorithm, malnutrition is diagnosed by a combination of at least one phenotypic and at least one etiologic criterion. Gender differences in nutritional indices may be relevant, especially variables assessing weight loss, nutritional intake and digestive symptoms, where different eating habits and symptom expression are known between the sexes. The aim of the study is to validate the GLIM criteria in patients with IBD, including the gender perspective, and to assess the influence of psychosocial factors.

Methods

Multicentre, prospective, observational, analytical study in non-hospitalised IBD patients. A total of 368 patients with a 1:1 male to female ratio will be included. At the baseline visit GLIM criteria will be assessed along with other nutritional parameters, clinical and demographic characteristics of IBD. Validation of the GLIM criteria will be done with the 6 and 9 month incidence of complications associated with malnutrition (hospitalisations, emergency department visits, medical consultations, IBD complications, surgery and quality of life impairment), with specific analysis by gender and type of IBD.

Results

To date, a total of 204 IBD patients have been included (104 women; 104 with Crohn's disease [CD], 97 with ulcerative colitis [UC] and 3 with non-specific colitis); with a median age of 52 (SD 14.3) years. The prevalence of malnutrition according to GLIM criteria was 18.1% and 44.1% of patients were at risk of malnutrition, 20.1% by phenotypic criteria and 24% by etiological criteria. In the subgroup analysis, 20.2% of CD patients and 16.5% of UC patients were malnourished according to GLIM criteria. Risk of malnutrition was found in 45.1% and 39.2% in CD and UC, respectively.

Conclusion

The prevalence of undernutrition according to GLIM criteria is higher in CD than in UC.
P1128 Reducing diagnostic delay of Extra-Intestinal Manifestations in patients with Inflammatory Bowel Disease: a comparative study between a multidisciplinary immune-mediated diseases outpatient clinic and conventional referral specialists
Authors: Nardone O M , Calabrese G , Peluso R , Foglia F , Megna M , Cacciapuoti S , La Mantia A , D'Alessandro E , Ferrante M , Villani G , Testa A , Bonacci L , Leo C , Rispo A , Castiglione F
Published: January 2024

Background

Extraintestinal manifestations (EIMs) can occur in up to 47% of patients diagnosed with inflammatory bowel disease (IBD); hence the early detection of EIMs in IBD patients is crucial to prevent structural damage. However, there is a substantial variation in the reported time to diagnosis of EIMs due to a lack of a standardised approach. We, therefore, evaluated the length of time to diagnose EIMs through an integrated immune-mediated diseases (IMIDs) outpatient clinic (IMID-C) compared to a standard outpatient clinic (SO-C). Secondary endpoint included the impact of diagnostic time on the time to therapy, thereby aiming for an early control of disease

Methods

We conducted a single-centre cohort observational study including IBD patients ≥18 yo presenting red flags for EIMs who underwent outpatient visits through a multidisciplinary IMIDs clinic between 2018-2022 and we compared this group to a historical cohort, with similar clinical features, who underwent conventional visits by individual referral specialists from 2017 to 2022. Diagnostic delay was defined as the period from the occurrence of red flags to diagnosis of EIMs. Survival curves were plotted for assessing the differences in terms of diagnostic delay and time to treatment between IMID-C and SO-C within 18 months.

Results

We enrolled 238 IBD patients; 127 were referred to the IMIDs Clinic Group (IMID-G) and 111 to the Standard Outpatient Clinic group (SO-C). Demographic details are summarised in Table 1. The average time to EIMs diagnosis was 2,48±1,8 months for IMID-C and 5,36±2,3 months for SO-C (p=0.005). In both groups, most patients (38,6% in IMID-C and 44 in SO-C) referred red flags for peripheral arthritis (PA). In IMID-C, chronic back pain was reported by 23,6% of patients, similarly in SO-C 27,9% had chronic back pain. Overall, the majority of patients received a diagnosis of PA (IMID-C=37,5%; SO-C=33,7%) and spondyloarthropathy (IMID-C=32,1%; SO-C=33,7%). Significantly, more patients in the IMID-C group (34, 26,8%) received treatment with immunomodulators in addition to their ongoing therapy compared to the SO-C group (17, 17,3%; p=0.04). Details of therapeutic strategies are summarized in Table 2. Survival curves revealed a significant reduction of diagnostic delay and time to therapy in IMID-C compared to SOC-C group (log-rank test, p<0.001)

Conclusion

Attending a dedicated IMIDs clinic can enhance the diagnostic process for EIMs in IBD patients, thereby reducing diagnostic delays. Disease-modification trials are eagerly awaited to assess the long-term impact on disease progression, quality of life and disability
P1190 Inflammatory Bowel Disease Treatment Economics: Assessing the Financial Ramifications and Striving for Healthcare Equity
Authors: Dosal Limon S K , Sánchez Rosado R R , Soto Llanes J O , Vela Torres A , Ramírez García G , Jiménez Bobadilla B , De León Rendón J L
Published: January 2024

Background

Inflammatory Bowel Disease (IBD) has emerged as a public health challenge. In addition to the health effects on patients, IBD also carries a significant economic impact. The diagnosis, treatment, and follow-up of IBD entail considerable costs for both patients and the healthcare system. Therefore, understanding the economic impact of this disease is crucial for making informed decisions about its management and resource allocation. The aim of this study was to determine the short-term (one month) and long-term (twelve months) economic impact of medical care and surgical treatment in patients diagnosed with IBD at a tertiary-level hospital in Mexico.

Methods

A retrospective study was conducted, which included 118 patients diagnosed with IBD and treated at the IBD Clinic of the "Dr. Eduardo Liceaga" General Hospital in Mexico over the past 12 months. The economic impact of both medical treatment (conventional and biological) and surgical treatment in managing IBD was evaluated. For the calculation of medical treatment costs, the unit costs of medications were based on maximum retail prices at a conventional pharmacy. Surgical treatment costs were based on the hospital's provided costs. Individual costs for each patient were recorded and tabulated, and the total cost for each treatment regimen was calculated at one and twelve months. Descriptive statistical methods were used to analyze the data to obtain measures of central tendency and dispersion.

Results

The average monthly cost of medical treatment for a patient with IBD is estimated to be $11,612.45 Mexican pesos (MXN), resulting in a total cost of $139,349.40 MXN over 12 months. Considering all our patients, the total cost of medical care reaches $16,443,229.20 MXN in 12 months. Regarding surgical treatment, there is an average cost of $626,847.45 MXN per surgical event in patients with IBD. The total cost of surgical treatment for our IBD patients, encompassing a total of 24 patients, amounts to $15,043,379 MXN. Therefore, medical treatment appears to be more cost-effective compared to surgical treatment (the total cost of medical treatment for the 121 patients over one year is $16,443,229.20 MXN, while the total cost of surgical treatment for the 24 patients is $15,043,379 MXN). In our institution, 95% of the IBD Clinic patients receive free medical care. This represents significant cost savings for patients.

Conclusion

This study provides evidence regarding the economic impact of medical and surgical treatment in patients with IBD. The results support the consideration of medical treatment as the more cost-effective option while emphasizing the significance of free medical care in improving equitable access and alleviating the financial burden on patients and their families.
P1204 Oral Streptococcus mutans isolates aggravated colitis in mice
Authors: Chen J , Yang C , Xu Y , Zhao Y , Wu J , Liu Y , Chen N
Published: January 2024

Background

The incidence of inflammatory bowel disease (IBD) is increasing year by year and the mechanism is unclear. A great number of studies have shown that the gut microbiota composition of IBD patients has changed and the diversity of gut microbiota decreases. The abundance of firmicutes decreases, and the abundance of Proteobacteria increases, which eventually leads to the immune disorders and intestinal inflammation. The mouth is the "gateway" of the digestive tract, which has various microbiota. The entry of extraneous microbiota from the mouth into the intestines play an important role in influencing the composition of the gut microbiota. The continuous disorder of the oral microenvironment (such as periodontitis and dental caries) are also closely related to intestinal inflammation.

Methods

A series of in vivo and in vitro experiments were conducted to investigate the effect and mechanism of S. mutans on colitis mice.

Results

S.mutans strain UA159 which is closely related to dental caries significantly aggravated colitis in DSS induced mice, as shown by body weight loss, shorter colon length, and increased inflammatory histological scores (Fig1A). UA159 up-regulated intestinal pro-inflammatory cytokines and inhibited the expression of barrier molecules in DSS mice (Fig1B). The proportion of adaptive immune cells (Th1, Th17) was up-regulated in intestinal lamina propria of UA159-administered mice (Fig1C-D).The fecal microbiota composition of UA159 mice was different from control group. The pro-inflammatory effects of UA159 on DSS mice disappeared when antibiotics were used to eliminate the intestinal microbiota. It is suggested that S.mutans may play a proinflammatory role by influencing the intestinal microbiota of mice (Fig1E).

We followed 55 IBD patients for more than 1 year and found that IBD patients with poor control had a higher proportion of S.mutans in saliva (Fig1F). S.mutans strains were isolated from IBD saliva samples and were found to cluster in different branches in the phylogenetic tree (Fig1G). S.mutans isolates have different pro-inflammatory effects on colitis mice and intestinal epithelial cells (Fig1H-I). Subsequent experiments are under way to further explore the mechanism leading to the differences of the pro-inflammatory effects.

Conclusion

Our study were the first to find that oral S.mutans has aggravated intestinal inflammation. S.mutans UA159 aggravated colitis in mice through damaging intestinal mucosal barrier function, enhancing immune response and disrupting intestinal microbiota (Fig1J). The difference in pro-inflammatory effect of S.mutans derived from different IBD patients saliva may be related to the individual clinical outcome.