bluuebunny/crossref_metadata_2025 huggingface dataset:
P344 What our patients are looking for - the common fields of interest in IBD patients: A Google Trends Analysis
Authors: Zarchi R , Elgressy A , Ben-Horin S , Kopylov U
Published: January 2022

Background

Inflammatory bowel diseases are varied in the way they present, progress and respond to treatment. IBD patients frequently complain about the lack of proper knowledge and support systems, this gap leads to an extensive online search for information. The aim of our study was to characterize the trends in IBD-related Google searches by exploring the Google Trends query tool

Methods

We retrieved worldwide Google Trends data related to Crohn’s Disease and Ulcerative Colitis over the past, 10 years (Jan, 2011 - Oct, 2021). The search terms selection was based on preferences and knowledge gaps identified by an online survey by the members of the of the israeli Crohn’s Disease and Ulcerative Colitis patients association, coupled with data from available literature and Google autocompletion data. We also compared the search volume of the two diseases using the “Topic” feature in google trends, which allows us to utilize google’s search terms aggregation by a specific topic. Google trends provide RSV (Relative Search Volume) over time, and over different regions. The results are normalized on a scale of, 0–100 (100 signifying the most highly-search item).We also compared the RSV for searches related to UC and CD.

Results

Out of the, 20 domains researched over, 370 months, the, 10 most searched domains in Crohn’s disease related searches was ’diet’(41.30%), ’cancer’(14.22%), ’weight’(7.52%), ’pregnancy’(4.44%), ’disability’(4.05%), ’COVID’(3.45%), ’alcohol’ (3.22%), ’vaccine’ (3.17%), ’stress’ (2.54%) and ’smoking’ (2.47%). The, 10 most searched domain in ulcerative colitis related searches was ’diet’ (41.72%), ’cancer’ (18.69%), ’weight’ (5.47%), ’pregnancy’(4.77%), ’smoking’(3.76%), ’alcohol’(3.63%), ’probiotics(3.27%), ’disability’(2.77%), ’stress’(2.62%) and ’covid’(2.12%). When focusing at the time period between March, 2020 and October, 2021, the most searched domain in crohn’s disease was ’COVID’(22.67%) followed by ’diet’(21.81%), ’cancer’(12.52%), ’vaccine’(10.70%), ’weight’(7.07%), ’disability’ (4.34%), ’alcohol’ (2.82%), ’pregnancy’ (2.67%), ’stress’ (2.22%) and ’biologics’ (2.17%). Over the same time span, the most searched domain in ulcerative colitis was ’diet’ (29.59%) followed by ’cancer’ (18.32%), ’COVID’ (11.84%), ’weight’ (6.32%), ’vaccine’ (5.75%), ’alcohol’ (4.07%), ’pregnancy’ (3.66%), ’disability’ (3.06%), ’smoking’ (2.61%) and ’probiotics’ (2.46%).

Conclusion

Patients have numerous interests related to their IBD disease. The most searched IBD-related item is diet, with COVID-19 leading since the break of the pandemic. Our results are a surrogate representation of the patient’s knowledge gaps and needs, and we suggest that IBD healthcare providers should focus their guidance on the issues identified by the patients as such.
P345 The Effectiveness of Ustekinumab and Vedolizumab as Third-line Therapy in Patients with Refractory Crohn’s Disease
Authors: Macaluso F S , Grova M , Saladino M , Demarzo M G , Privitera A C , Giangreco E , Garufi S , Renna S , Casà A , Ventimiglia M , Cappello M , Fries W , Orlando A
Published: January 2022

Background

There is no head-to-head trial comparing ustekinumab (UST) and vedolizumab (VDZ) in Crohn’s disease (CD). Recently, real-world studies evaluated the two biologics in patients refractory to anti-TNF therapy, i.e. as second-line agents. Conversely, no study specifically focused on the effectiveness of UST and VDZ as third-line agents, i.e. after failure with at least one TNF-α inhibitor plus failure with VDZ or UST. We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ in these highly-refractory patients with CD.

Methods

Data of consecutive patients with CD treated with UST and VDZ as third-line therapy until October, 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The effectiveness was evaluated at, 8, 26, and, 52 weeks, and as treatment persistence at the end of follow up. The clinical outcomes were steroid-free clinical remission (SFCR - Harvey-Bradshaw Index <, 5 without steroid use) and clinical response (CR - reduction of the Harvey-Bradshaw Index ≥, 3 points with a concomitant decrease of steroid dosage compared with baseline). Multiple logistic regression models were build to find independent predictors of effectiveness, including the use of UST and VDZ as candidate predictors.

Results

143 patients (UST: n=113; VDZ: n=30) were included. After, 8 weeks, SFCR was reported in, 38.1% of patients treated with UST and in, 43.3% of patients treated with VDZ (p=0.75), while CR was reported in, 61.9% of patients treated with UST and in, 60.0% patients treated with VDZ (p=1.00). After, 26 weeks, the rates of SFCR and CR were, 41.6% for UST and, 50.0% for VDZ (p=0.60), and, 61.4% for UST and, 66.7% for VDZ (p=0.81), respectively. After, 52 weeks, the rates of SFCR and CR were, 51.8% for UST and, 57.1% for VDZ (p=0.78), and, 65.9% for UST and, 71.4% for VDZ (p=0.77), respectively. Lack of difference in effectiveness between the two drugs at any time point was confirmed by multiple logistic regression models. After, 26 weeks, 88.7% of patients treated with UST and, 81.4% of patients treated with VDZ were still on treatment. Univariable Cox survival analysis showed a higher probability of treatment discontinuation for VDZ compared with UST (HR for VDZ:, 2.66; p=0.008), even if such difference was not confirmed at the multiple Cox proportional hazard regression model (HR for VDZ:, 1.94; p=0.08), where only age (HR, 0.98; p=0.04) and use of systemic steroids at baseline (HR, 3.29; p=0.003) were found to be independent predictors of treatment discontinuation.

Conclusion

This is the first real-world study assessing VDZ and UST as third-line therapy in patients with CD. Both drugs showed surprisingly high effectiveness, without significant differences between them.
P351 Allogenic adipose-derived mesenchymal stem cells (darvadstrocel) in Japanese patients with complex perianal fistulas in Crohn’s disease
Authors: Watanabe K , Mizushima T , Okita Y , Sugita A , Nakaya R , Shibata M , Yamaguchi T
Published: January 2022

Background

Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since, 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD).

Methods

Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from, 9 sites in a phase, 3, open-label, single-arm, uncontrolled study. Patients could have, 2 internal and, 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after, 24 and, 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24.

Results

22 patients (mean age, 36.4 years, 63.6% male, mean duration of CD, 11.3 years) were enrolled. A half (11/22) had, 1 internal opening (IO) and, 2 external openings (EO) followed by, 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and, 1IO-3EO (2/22)., 59.1% and, 68.2% achieved combined remission at Week, 24 (primary endpoint) and Week, 52, respectively.

Up to Week, 52, 90.9% (20/22) experienced adverse events (AE), and, 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation.

Conclusion

52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in, 68% (15/22) and partial closure in, 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.
P366 Exclusive enteral nutrition drives protective microbiome modulation in paediatric Crohn’s Disease
Authors: Häcker D , Siebert K , Metwaly A , Hölz H , De Zen F , Köhler N , Pauling J K , Matchado M , List M , Schwerd T , Haller D
Published: January 2022

Background

Exclusive enteral nutrition (EEN) is a first-line induction therapy for paediatric Crohn’s disease (CD). Although the protective mechanisms remain unclear, previous studies showed substantial changes in microbiome composition in response to EEN. We aim to assess the protective function of EEN and its impact on gut microbiome signatures in paediatric CD.

Methods

We prospectively followed, 15 newly diagnosed paediatric CD patients aged, 3–18 years between, 01/2019 –, 08/2021. Patients were treated according to international guidelines including EEN therapy for, 6–8 weeks, followed by a gradual re-introduction of solid food and concomitant start of maintenance treatment. Disease activity and inflammatory biomarkers were monitored during, 12-months follow-up. 16S rRNA gene sequencing and targeted/untargeted metabolomics was performed from stool samples collected weekly during EEN and monthly thereafter (n = 261). Dietary modulation and clinical activity of patient-derived stool microbiota were studied by ex-vivo faecal fermentation and after faecal microbiota transplantation (FMT) into germ free (GF) IL10-/- mice.

Results

All patients achieved remission with EEN therapy but, 6/15 had resuming CD activity within, 6 months. Longitudinal microbial and metabolite profiling of stool samples showed highly individualized responses to EEN without coherent signatures. Integrated multi-omics data analysis showed an enrichment of long-chain fatty acids in patients under EEN, which correlated with a reduced abundance of Lachnospiraceae, compared to patients under regular diet. Faecal microbiota from CD patients with active disease (baseline or relapse) or inactive disease (EEN-induced remission) were exposed to EEN-like or dietary control formulations in continuous ex-vivo cultures. EEN-like formulation induced protective changes in the patient-derived baseline microbiota confirmed by the absence of disease activity after FMT in GF IL10-/- mice. Mice colonized with baseline microbiota after ex-vivo EEN exposure showed a decreased abundance of Bacteroides, Akkermansia, Blautia and an increase of Lachnoclostridium and Parabacteroides in comparison to those colonized directly with patient’s baseline microbiota. In contrast, EEN-like diet failed to mitigate the aggressive behaviour of relapse microbiota when transferred into GF IL10-/- mice which was in line with an inability to cause significant compositional changes.

Conclusion

Our data show that clinical efficacy of EEN in paediatric CD is accompanied by temporal and individual gut microbial and metabolite changes. The combined findings of continuous culture and gnotobiotic mouse models point towards a direct protective role of EEN-modulated patient microbiomes in regulating intestinal inflammation.
P378 Rectal bleeding and stool frequency improvement with tofacitinib dose escalation to, 10 mg BID in patients with Ulcerative Colitis following loss of response on tofacitinib, 5 mg BID maintenance therapy: Results from OCTAVE Open
Authors: Allegretti J R , Gecse K B , Chiorean M V , Argollo M , Guo X , Lawendy N , Su C , Mundayat R , Paulissen J , Salese L , Irving P M
Published: January 2022

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In the tofacitinib UC clinical programme, patients who responded to tofacitinib, 10 mg BID during induction, and experienced treatment failure whilst receiving tofacitinib, 5 mg BID during maintenance (OCTAVE Sustain) and subsequently received tofacitinib, 10 mg BID in the open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612), comprised the dose escalation subpopulation. The efficacy and safety of tofacitinib in the dose escalation subpopulation have been previously reported.1 Here, we evaluated patient-reported outcomes to assess rectal bleeding and stool frequency improvement in the dose escalation subpopulation in OCTAVE Open.

Methods

The following efficacy endpoints based on the Mayo subscores were analysed in the overall dose escalation subpopulation and by prior tumour necrosis factor inhibitor (TNFi) failure status: rectal bleeding improvement (≥1 point decrease in rectal bleeding subscore [RBS] from OLE study baseline) and stool frequency improvement (≥1 point decrease in stool frequency subscore [SFS] from OLE study baseline), up to Month (M)6 in the OLE study (full analysis set, non-responder imputation). Changes from baseline in partial Mayo score (PMS), RBS and SFS at M1, by M2 clinical response status, were also analysed (as observed).

Results

In OCTAVE Open, 57 patients were included in the dose escalation subpopulation, of which, 28 (49.1%) had prior TNFi failure. Overall, at M1 and M6, of OCTAVE Open, 59.6% and, 66.7% of patients had rectal bleeding improvement, respectively (Figure, 1). Corresponding values for stool frequency improvement were, 50.9% and, 64.9%. At most time points, rates of rectal bleeding and stool frequency improvements were similar in patients with and without prior TNFi failure. Patients with a clinical response at M2 had a numerically greater mean decrease from baseline in PMS, RBS and SFS at M1 than those without (Figure 2).

Conclusion

In this post hoc analysis, in patients with UC who had loss of response after, 8–52 weeks of treatment with tofacitinib, 5 mg BID (following reduction from induction tofacitinib, 10 mg BID), dose escalation back to, 10 mg BID generally resulted in rectal bleeding and stool frequency improvement in the majority of patients by M1, which was maintained to M6, regardless of prior TNFi failure status. Furthermore, early improvement in RBS and/or SFS at M1 may indicate likelihood of recapturing response at M2 with dose escalation from tofacitinib, 5 to, 10 mg BID.

Reference

1. Sands BE et al. Aliment Pharmacol Ther, 2020;, 51:, 271–280.
P383 Ustekinumab as an opportunity for refractory Ulcerative Colitis patients
Authors: Iborra M , Soutullo C , Gimeno M , Bastida G , Aguas M , Cerrillo E , Sáez-González E , Garrido A , Mínguez A , Bordetas J , Nos P
Published: January 2022

Background

There are limited data in real-life of ustekinumab (USK) used in ulcerative colitis (UC). The aim of this study was to assess the effectiveness and safety in clinical practice of USK in UC in the medium and long-term.

Methods

Observational study in UC patients who received USK at the recommended dose based on weight ~6 mg/kg IV week, 0.90 mg SC week, 8 and maintenance, 90 mg SC every, 8 or, 12 weeks and with, 1 year of follow-up. The partial Mayo score (PMS) was used to assess clinical remission (PMS≤, 2). The PMS, C-reactive protein (CRP) and faecal calprotectin (FC) values ​​were recorded at baseline and after, 8, 16, 24 and, 52 weeks. Dose adjustment was performed by the measure of UST trough levels by ELISA, when patient lost clinical and/or biochemical response and the levels were low (<1.3 µg/ml). Demographic, clinical, biochemical and endoscopic data, previous treatments, adverse events (AEs), surgeries and hospitalizations, were documented.

Results

Twenty-three patients with UC were analysed. (Table, 1). All patients had received previous biological treatment:, 52% ≥2 anti-TNF, 65% vedolizumab and, 30% JAK inhibitors. Treatment discontinuation occurred in, 3 patients (13%). The persistence was, 83% and, 79% at, 6 and, 12 months (Figure, 1). During follow-up, 12 patients (52%) maintained standard dose of USK. Dose adjustment was performed in, 13 patients (56%):, 3 (13%) required intravenous UST reinduction and, 10 (43%) required dose escalation (8 by shortening the interval between doses and, 2 by switching to intravenous USK administration). Clinical remission was reached in, 61%, 58%, 56%, 79% of the patients after, 8, 16, 24, 52 weeks, respectively. Normal CRP (<5mg/L) and FC (<150 µg/g) levels were achieved in, 76%, 93% and, 80% and in, 35%, 31% and, 40% of patients after, 8, 24, 52 weeks, respectively. Five of, 6 patients who had endoscopy before and after treatment showed endoscopic Mayo subscore ≤1. There were, 2 AEs, 1 hospitalization, and, 1 colectomy during follow-up.

Conclusion

This study demonstrates the safety as well as the clinical, biological and endoscopic effectiveness of USK adjusted by levels in real life in a highly refractory UC cohort.
P386 Predictive models for assessing the response to ustekinumab in Crohn’s disease patients
Authors: Hubert A , Bottieau J , Toubeau J F , Franchimont D , Vallée F , Liefferinckx C
Published: January 2022

Background

The loss of response to biologics remains a clinical challenge for which the discovery of predictive factors is helpful. In this direction, exploiting tree-based models on top of logistic regression (LR) allows to uncover unexpected valuable predictors. The aim of the study is to develop performant predictions of ustekinumab (USK) response at one year of follow-up in a cohort of Crohn’s disease (CD) patients using benchmark logistic regression (LR) and tailored tree-based techniques, Random forest (RF) and Gradient Boosting Decision Trees (GBDT).

Methods

This is a retrospective study based on a cohort of, 80 CD patients treated with USK. Inputs include demographic data, disease characteristics as well as pharmacokinetics, clinical and biological parameters at baseline, week, 8 and, 16. After one-year follow-up, both clinical outcome (achieved in case of USK maintenance without optimization, n=80) and endoscopic outcome (achieved in case of SES-CD<10, n=52) are evaluated. The inputs are firstly ranked via the p-values for LR method and the impurity criterion for the tree-based ensemble methods. Then, the optimal subset of inputs for both methods is selected following a sequential feature selection. Due to the limited size cohort, a nested cross-validation framework was applied to avoid bias and overfitting. The performance of the final models is evaluated using the area under the ROC curve (AUC) with standard deviation (SD), sensitivity (Se) and specificity (Sp). All the analyses are performed with Python, 3.6, 6 using the packages statsmodels and Scikit-learn.

Results

Input data characterizing the CD cohort are presented in Table, 1. At one-year follow-up, clinical and endoscopic outcomes were achieved in, 56.2% (n=45/80) and, 69% (n=, 36/52), respectively. Table, 2 summarizes the predictive model characteristics at the different timepoints. Whatever the outcome, predictive models exhibited an increased accuracy over the induction timepoints. At week, 16, a multivariate LR allowed to predict endoscopic outcome with an AUC, 0.86±0.12, Se, 83% and Sp, 70%. The explanatory variables were CRP level at week, 8 and, 16, lymphocyte count at week, 8 and USK trough levels at week, 16. The best model to predict endoscopic outcome was obtained by RF with an AUC of, 0.92 ±0.08, Se, 91% and Sp, 75%. The key inputs were lymphocyte count at baseline.

Conclusion

This study highlighted the added value of applying tree-based models for the development of accurate predictive models. More specifically, the evolution of biological markers during induction as well as USK trough levels at week, 16 are relevant factors to predict endoscopic outcome among CD patients treated with USK
P391 Unpacking the different popular diets for pediatric Crohn’s disease - concerns around nutritional adequacy
Authors: Carmody E , Haskett J , Parkinson-McGraw L , Grover Z , Martinez A , Rashid M , Otley MD MSc FRCPC A
Published: January 2022

Background

The first line treatment for inducing remission in pediatric Crohn’s disease (CD) is Exclusive Enteral Nutrition (EEN), where a patient drinks a nutritionally complete formula exclusively for, 6 to, 12 weeks. Despite the effectiveness of EEN, some patients may experience challenges including taste fatigue, monotony, and a lack of social participation with meals. Given these challenges, patients may turn to popular or fad diets for managing their disease. These diets are often restrictive, eliminating a number of foods and exacerbating the risk of underlying nutrient deficiencies in this patient population.

Methods

These case studies involved a nutrient analysis of evidence-based and popular diets for CD, including Crohn’s Disease Exclusion Diet (CDED), CD-TREAT, Specific Carbohydrate Diet (SCD), IBD Anti-inflammatory Diet (IBD-AID), Autoimmune Protocol (AIP) Diet, Gut and Psychology Syndrome (GAPS) Diet, and low FODMAP. Four cases were selected with mild-moderate CD:, 11-year-old and, 16-year-old, both male and female. A nutrient analysis of sample menus of each diet was completed using Food Processor version of, 11.6.0 by ESHA Research. Results were compared to age and gender specific Dietary Reference Intakes (DRIs), population-based dietary intake data, and Health Canada Dietary Guidelines.

Results

Data are presented for Case, 1, 11-year-old male. Findings were comparable to other age and gender cases. As compared to Acceptable Macronutrient Distribution Ranges (AMDRs), there was a higher percentage of energy from fats and lower from carbohydrates for the SCD (% kcal, fat and carbohydrate respectively:, 59%;, 30%), IBD-AID (52%;, 37%), AIP Diet (50%;, 20%) and GAPS Diet (60%, 21%). Saturated fat intake exceeded recommendations (>10% of energy intake) for CDED (% kcal, 14%) CD Treat (17%), SCD (11%), AIP Diet (15%) and GAPS Diet (20%). Both vitamin D and/or calcium intake were below the Recommended Dietary Allowance (RDA) respectively for CDED (% RDA, vitamin D and calcium respectively:, 89%;, 86%), SCD (23%;, 53%), AIP Diet (14%;, 23%), low FODMAP Diet (4%, 96%) and GAPS Diet (calcium, 58%). Adolescent females versus males between the ages of, 14–18 years may be at greater risk of inadequate nutrient intake, given the general increase in nutrient requirements yet lower caloric needs.

Conclusion

Given the increase in awareness and interest in popular diets for Crohn’s disease, it is imperative that clinicians are aware of the risks of inadequate nutrient intake with restrictive diets.
P404 Underrepresentation of minorities and lack of race reporting in ulcerative colitis drug development clinical trials
Authors: Sedano R , Hogan M , McDonald C , Aswani-Omprakash T , Ma C , Jairath V
Published: January 2022

Background

Historically, inflammatory bowel disease (IBD) trials report high enrollment rates for white-caucasian patients. To promote initiatives towards diversifying patients enrolled in clinical trials, we assessed the reporting of race/ethnicity of patients enrolled in pharmaceutical clinical trials for ulcerative colitis (UC).

Methods

A previous systematic review of all placebo-controlled trials in adult patients with UC examining different therapeutic drug classes was performed from inception to December 2020.

Trial and patient characteristics were summarized according to the type of variable. Categorical variables were summarized by displaying the number and percentage of trials or participants for each category. Continuous variables were summarized by displaying the weighted mean, weighted standard deviation, and range. Means and standard deviations (SD) were weighted by the number of participants in each trial.

Results

Descriptive statistics of trial and patient characteristics for, 95 induction trials and, 29 maintenance trials are summarized in Table, 1. Race was reported in, 37.9% (36/95) of induction studies, with most participants being White (86.3%;, 8610/9976). Furthermore, 21/36 (58.3%) studies reported race as White vs. non-White participants; and, 15/36 (41.7%) studies provided further breakdown, including Black (115/3414 patients [3.4%]), Asian (448/4136 patients [10.8%]), and “Other” (127/4136 patients [3.1%]). Moreover, 3/36 studies misreported race as ethnicity and, only, 3/36 studies reported ethnicities correctly, classifying patients as Hispanic/Latinx vs. Non-Hispanic/Latinx. For maintenance trials, 34.5% (10/29) studies reported race, with majority of participants being White (85.6%;, 2778/3246). Additionally, 6/10 studies reported only a White vs. non-White participants comparison, while, 4/10 reported other races, including Black (45/1145 patients [3.9%]), Asian (40/888 patients [4.5%]), and “Other” (26/1145 patients [2.3%]). No studies reported ethnicity.

Conclusion

Given the increasing burden of IBD in developing countries, differences amongst racial and ethnic groups are important to understand since they can influence disease phenotype, response to therapy, and safety outcomes.1 We found poor race reporting in UC clinical trials and observed that the vast majority of participants enrolled were White. These findings suggest that the population prevalence of UC amongst different racial groups is not reflected in clinical trial populations, being important to raise awareness of the existing barriers that prevent patients from accessing clinical trials. Reporting of race and ethnicity in UC clinical trials should be mandatory, and a requirement to enroll a certain percentage of non-White patients should be considered.2
P412 Drug persistence and endoscopic, histologic and biochemical remission rates among patients following ileal pouch-anal anastomosis treated with biologic therapy: Results from a prospective patient cohort
Authors: Ollech J , Yanai H , Avni-Biron I , Snir Y , Banai H , Broitman Y , Goren I , Wasserberg N , White I , Dotan I
Published: January 2022

Background

Patients with ulcerative colitis (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) may develop chronic pouchitis or Crohn’s like disease of the pouch (CLDP). These patients may need treatment with biologic therapies. Data regarding treatment persistence as well as clinical, biochemical, endoscopic, and histologic remission rates are lacking

Methods

Patients after IPAA were followed prospectively at a dedicated pouch clinic. Patients with CP or CLDP who were antibiotic/steroid-refractory or dependent, had antibiotics/steroids side effects or had extraintestinal manifestations were treated with biologics. Clinical, endoscopic, histologic, and laboratory data were extracted from medical records at the last follow-up. Patient’s quality of life (QoL) was assessed by visual analog scale (VAS), with scores of, 0–100 (higher=better QoL). Time to biologic therapy discontinuation was measured for all patients; patients were censored if still on biologic therapy at the time of the last follow-up. Biochemical remission was defined as C-reactive protein (CRP)<, 0.5 mg/dl and a fecal calprotectin (FC)<, 150 ug/dl with a normal albumin level. Endoscopic and histologic remission was defined by the pouchitis disease activity index (PDAI) as an endoscopic subscore ≤2 and a histologic subscore, 0 or, 1, respectively.

Results

The prospective cohort constituted, 130 patients. Females:, 73 (56%). Before IPAA, most (70%) patients had pancolitis, 95% received steroids and mesalamine, and, 37% - biologic therapies. Median follow-up after ileostomy closure:, 16 years. Biologic therapy was started in, 28 patients (22%) due to CP or CLDP. The first line biologic for all, 28 patients was anti-TNF’s and, 9 patients received more than one line of biologics. Median time to commencing biologics:, 130 months. Median first-line biologic drug persistence:, 222 weeks. Among patients treated with biologic therapy, at the last clinic visit, median CRP was, 0.58 mg/dl, median FC:, 255ug/g, median HB:, 12.46 mg/dl, and median albumin was, 4.5 mg/dl.Median PDAI endoscopic and histologic scores were, 2; median VAS rating was, 80. Biologic remission criteria were fulfilled by, 43% of patients (N-12). An additional, 43% (N-12) were also in endoscopic remission with an endoscopic PDAI subscore of, 2 or below, and an additional, 29% of patients (N-8) were in histologic remission with a histologic PDAI score of, 0 or 1.

Conclusion

Biologics reintroduction after IPAA was relatively common, albeit after a very long interval. Biologic therapy was effective, with a sizable proportion of patients in biochemical, endoscopic, and histologic remission. Likewise, drug persistence was long. We suggest that early initiation of biologic therapy in certain patients may be prudent.
P424 Uptake of a switching program for patients receiving intravenous infliximab and vedolizumab to subcutaneous preparations
Authors: Alice H , Gemma B , Selinger C P
Published: January 2022

Background

Recent trials support the clinical efficacy and safety of subcutaneous (sc) biologic treatment for IBD maintenance therapy. Administration of sc injections could reduce the financial burden and time required to attend for infusions and allow IBD service providers to manage increasing clinical demand. We evaluated the uptake and rationale for choosing to switch from intravenous (iv) infusions to sc injections, including the impact of the Covid-19 pandemic on IBD service provision.

Methods

All adult patients receiving standard dosing maintenance iv Infliximab or Vedolizumab therapy at a tertiary IBD centre were offered a switch to the respective sc formulations. We investigated the uptake of the switch from iv infusions to sc injections and utilised a standardised patient questionnaire to determine the rationale for switching to sc injections or not, and to identify areas for improvement in IBD service provision for the switching process.

Results

In a cohort of, 232 eligible patients (258 total patients, 190 infliximab, 68 vedolizumab, 26 no longer eligible), 58% of patients receiving Infliximab and, 59% of patients chose to switch to sc treatment. Of the, 26 ineligible patients, 6 were switched to an intensified treatment schedule, 12 switched to a different biologic, 2 moved out of area, 5 had treatment stopped for clinical reasons and, 1 required operative treatment. There were no significant predictors for willingness to switch relating to patient age, sex, diagnosis, drug, line of treatment or duration of treatment (p>0.05). Early results from patient questionnaires (n=23) demonstrate that a decision to switch was not influenced by the impact on their mental health, Covid-19 risk, the impact on wider IBD service provision or financial savings, but, 70% of switchers did report that time savings influenced their decision. A minority of patients reported feeling pressured to switch (10% switchers and, 15% non-switchers) or had concerns about the safety (20% switchers, 0% non-switchers) and efficacy (40% switchers, 31% non-switchers) of sc injections. The majority of patients feel they were provided with sufficient

Conclusion

Switch uptake rates were, 58% with, 90% of patients eligible to switch. We found no evidence that a decision to switch was influenced by age, sex, diagnosis, drug, line of treatment or duration of treatment. Non-switchers value face-to-face support at the IBD unit highly, and switchers value the time saved by administering injections at home. Switching to sc formulation not only provided patients with a choice of saving time usually required for iv administration but also reduced pressure in an overstretched IBD service.
P427 Exploring phenotype and treatment of inflammatory bowel disease in the elderly
Authors: Gaglani R , Balarajah S , Williams H , Hicks L
Published: January 2022

Background

On a background of an ageing population, approximately, 10–15% of new cases of IBD are diagnosed in patients over the age of, 60.1,2 Studies show IBD in the elderly is increasing, including both the groups of patients diagnosed at a younger age, and de novo elderly IBD.

Older patients are more likely to have other co-morbidities and be concurrently prescribed other medications, which may impact the choice and timing of therapies for their disease. It is not clear if IBD in older age is different phenotypically from that in younger counterparts, and whether current management algorithms can be used safely in this cohort.

Aims of the study were to evaluate the IBD phenotype and use of therapies in the elderly (≥75 years) and younger (18–74 years) patients, and to assess for differences in adverse outcomes between both cohorts on immunosuppressants (IMs) and/or biologics.

Methods

A retrospective study was performed on, 173 IBD patients at Imperial College Healthcare NHS Trust over a two-year period., 91 elderly IBD patients were compared with, 82 younger patients, matched by gender and IBD subtype. Analysis included chi-squared tests with Fisher’s correction.

Results

There were, 55 elderly patients and, 51 younger matched patients with ulcerative colitis (UC) where no differences in disease extent, remission or surgeries were seen. There were, 36 elderly patients and, 31 younger matched patients with Crohn’s disease (CD). There was less ileocolonic disease in the older CD cohort compared to younger patients (27.8% versus, 51.6%, p=0.046) (figure 1).

Medication use in UC was the same regardless of age. There was significantly higher use of IMs and biologics in younger patients with CD (51.6%) versus the older cohort (25%, p=0.047) (figure 2).

In elderly patients with CD, a significantly greater mortality was seen in patients on IMs/biologics (27.3%) than those not on these medications (8%, p=0.023) (figure 3). The rate of VTE was higher (18.2% versus, 0%) in those on these treatments with a trend towards significance.

Conclusion

Overall, this retrospective study demonstrated that elderly IBD patients in this cohort appear to be mostly phenotypically similar to younger patients. However, elderly Crohn’s patients were less likely to be escalated to IMs/biologic treatments than their younger comparators. In view of the higher rate of adverse events recorded in the Crohn’s group managed with these treatments, this may be justified. Further, larger studies in the long-term outcomes of these patients are required.

Reference

1. Charpentier C et al. Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut., 2014;63(3),423–432
P443 Trough concentration response in infliximab and adalimumab treated children with IBD following treatment adjustment: A pharmacokinetic model
Authors: Levi R , Matar M , Zvoluni M , Shamir R , Assa A
Published: January 2022

Background

In patients with IBD, data on trough concentration (TC) response to adjustments in anti-TNFα treatment are scarce.

Methods

We included pediatric patients with IBD who were treated with anti-TNFα agents from, 2015 to, 2020 and had sequential monitoring of TC. Treatment adjustments were detected and subsequent changes in TC were recorded (next infusion for infliximab and up to, 8 weeks TC measurement for adalimumab). Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded.

Results

For the entire cohort (86 patients), median age at diagnosis was, 13.2 (10.7–14.9) years (Females, 48%; Crohn’s disease, 72%). For infliximab, 58 patients had, 201 interval changes (98 decrease and, 103 increase) and, 26 had dose increase. Dose increase resulted in TC change in the same direction but TC changes could not be predicted due to significant variability (p=0.9). This variability could not be attributed to any specific variable.

Interval decrease: Median TC pre adjustment was, 4.3 mcg/ml (IQR, 3.1–6.9 mcg/ml). For every, 10% decrease in interval, TC was increased by, 1.6 mcg/ml (B=, 1.6, 95% CI;, 0.9–2.4; p<0.001) or by, 57.2% (B=57.2, 95% CI;12.8–124.6; p=0.014). The presence of perianal disease was associated with attenuated response to interval decrease (diminished TC increase), p=0.001. Interval increase: Median TC pre change was, 12.6 mcg/ml (IQR, 9.5–12.1 mcg/ml). For every, 10% increase in interval, TC was decreased by, 0.66 mcg/ml (B=, 0.66, 95% CI;, 0.2–1.2; p=0.01) or by, 4.2% (B=, 4.2, 95% CI;, 2.0–6.4; p<0.001). The diagnosis of Crohn’s disease (VS. diagnosis of UC) was associated with reduced response to interval increase (diminished TC decrease), p=0.012.

For adalimumab, 28 patients had, 31 events of interval decrease from every, 2 weeks to every week and, 12 events of interval increase back to every, 2 weeks. Interval decrease resulted in increased median TC from, 4.5 (3.5–5.3) mcg/ml to, 8.1 (6.5–10.5) mcg/ml (X1.8) while interval increase resulted in TC change from, 15.5 (12.8–18.6) mcg/ml to, 9.7 (6.5–14.6) mcg/ml (:1.6). Changes in adalimumab TC were consistently significant (p<0.001). Increase in delta TC was associated with younger age (p=0.018), lower body surface area (p<0.001) and with the absence of perianal disease (p=0.001).

Laboratory measures (CRP, albumin- mostly within normal limits) were not associated with TC response for both agents.

Conclusion

Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab but not for infliximab. Thus, following infliximab adjustment, TC should be measured in-order to assess adequate TC response.
P444 COVID-19 risk factors, infection course and vaccination among patients with inflammatory bowel disease based on a Hungarian cohort
Authors: Farkas K , Matuz M , Kata D , Földesi I , Resál T , Bacsur P , Szántó K , Kolarovszki-Erdei D , Rutka M , Fábián A , Bor R , Szepes Z , Sarlós P , Miheller P , Zacháry A , Molnár T
Published: January 2022

Background

Inflammatory bowel disease potentially elevates the risk of infections, furthermore, disease activity and medical treatment(s) can increase the risk as well. However, both international data and recent studies do not confirm these preliminary conceptions regarding the SARS-CoV-2 infection. In addition, a number of studies have reported that less antibodies are produced against the virus in IBD patients. In January, 2021, the vaccination campaign has begun in Hungary as well, however, questions have been raised about the effectiveness and safety of the vaccine.

Methods

In this multicentre study, we assessed the prevalence and risk factors of COVID-19 infection, the willingness to receive COVID-19 vaccine and the efficacy of vaccination among IBD patients receiving biological therapy, based on a cross-sectional questionnaire-based study. To assess safety and antibody response to COVID-19 vaccines, we conducted a prospective study in the same Hungarian IBD centers. IgG antibody was quantified to SARS-CoV-2 spike protein and nucleocapsid, 1 week before and after the first vaccine and, 4 and, 8 weeks after the second vaccinane, respectively.

Results

472 patients were enrolled in the first part of our study. SARS-CoV-2 infection was confirmed in, 16.9% of patients. Wearing gloves and masks were found to be effective in preventing infection (p=0.02; p=0.005), avoidance of communal areas had no effect on infection rates. Male sex increased the risk (p=0.008) of viral infection. Based on subjective complaints, UC patients had a worse disease course (p=0.002). Biological therapies did not increase the risk of infections. Patients vaccinated with mRNA vaccine had a significantly higher spike protein antibody titer one month after the second vaccination (p=0.004) compared to other vaccine types (Sinopharm©, Sputnik V©, Astra Zeneca©). Seropositivity was detected in, 98% of patients. Sinopharm© vaccination triggered the lowest number of side effect (p<0.001). SARS-CoV-2 infection induced relapses more frequently than vaccinations.

Conclusion

Face mask was the most effective preventive tool. The risk of infection was not increased by biological therapy, therefore therapy discontinuation is not justified. Almost every vaccinated patient developed seropositivity two month after vaccination independently from the type of the vaccine, however, spike protein antibody was significantly higher following mRNA vaccinations.
P446 Long-term Clinical Effectiveness And Stoma Outcome Of Fecal Diversion In Refractory Crohn’s Proctitis
Authors: Benammi S , Perry W R , Calini G , Abdalla S , Shawki S F , Larson D W , Mathis K L
Published: January 2022

Background

Proctectomy is often recommended when Crohn’s proctitis becomes refractory to medical therapy. However, some surgeons offer a temporary diverting stoma in an effort to avoid a permanent stoma. The long-term efficacy of this approach is not well-established. Our aim was to determine the long-term effectiveness of fecal diversion in patients with refractory Crohn’s proctitis.

Methods

This retrospective study included all patients with Crohn’s proctitis who underwent formation of a diverting ileostomy or colostomy for refractory disease from, 1998 to, 2019 in Mayo Clinic Rochester MN. Outcomes were disease recurrence, rate of stoma closure, and proctectomy. Univariate comparisons among categorical variables were performed with Pearson’s Chi-square and continuous variables using the student t-test. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis. Multivariable analysis of risk factors for proctectomy and permanent stoma was achieved with logistic regression.

Results

Ninety-seven patients (55.7% female) were included. Ileostomy was the most common stoma type (88.7%, n=86), and colostomy was (11.3%, n=11) (Table.1). Median follow-up was, 4 years (range, 0–14). Active Crohn’s at follow-up was reported in, 68.1%. Only, 41.2% of patients underwent attempt at stoma reversal, and, 42.3% required a proctectomy (median, 19.5 months after diversion). At last follow-up, 29.9% were stoma-free, 42.3% had a new permanent stoma, and, 27.8% had the original diverting stoma (Fig.1). The multivariable predictors of proctectomy and permanent stoma were the recurrence of active CD after diversion and the need for other CD-related surgery following stoma creation (Table.2). The limitations of the study are its small sample size and its retrospective nature. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis (Fig.2).

Conclusion

Diversion is effective at alleviating symptoms of Crohn’s proctitis in selected patients but does not significantly change disease outcome. Only a small number can avoid a long-term stoma.
P455 Aminosalicylates in Ulcerative Colitis: old but gold?
Authors: Sequeira C , Santos I , Coelho M , Teixeira C , Mangualde J , Cremers I , Oliveira A
Published: January 2022

Background

The clinical course of ulcerative colitis (UC) is characterized by periods of exacerbation and remission. 5-aminosalicylic acid (5-ASA) remains the treatment of choice in patients with mild-to-moderate UC, due to its beneficial effect in preventing relapse. Treatment options (immunomodulators [IMM] and biological agents) have increased, so it is important recognizing patients at risk of medical therapy failure that can appropriately optimize treatment escalation for better control of the disease. Little is known about the long-term course of the disease among patients in remission with 5-ASA.

Aims

To assess long-term efficacy of 5-ASA (no IMM, biological therapy or colectomy) and to identify predictive factors of non-response.

Methods

An observational, retrospective, single-centre, case-control study was performed. All consecutive patients with UC followed in our Hospital from January 2000 until June 2020 initially treated with 5-ASA (±steroids) with a minimum follow-up of 1 year were screened for eligibility. Exclusion criteria were 5-ASA toxicity/intolerance or initial treatment with IMM/biologic agents.Time until step-up was recorded. Demographic, clinical, endoscopic, biochemical, and histological variables at the diagnosis were recorded and a Cox regression was performed to identify predictive factors for step-up strategy.

Results

218 patients (mean age 41,4±14,6 years; 54,5% female; mean follow-up10,1±1,9 years) were analysed, 28% needed treatment with biologics or IMM, mainly due to steroid-dependence. Among “5-ASA responders”, 72% and 48% had sustained endoscopic and histological remission, respectively. The probability of step-up at 1 year, 5 years and 10 years was 10, 18 and 25%, respectively. “Step-up patients” had higher rates of hospitalization, disease extent progression, extraintestinal manifestations and colonic stenosis and/or pseudo-polyps (p<0,05). Montreal E3 (HR:2,31;95% CI: 1,12-4,68), steroids at first flare (HR:3,45;95% CI: 1,26-7,29), lower 5-ASA maintenance dose (HR: 1,97;95%;CI:1,12-3,29), lower haemoglobin level (HR:1,45;95% CI: 1,11-3,24) and DUBLIN Score≥4 (HR:1,81;95% CI: 1,269-4,59) were factors associated with the step-up strategy, in multivariate analysis.

Conclusion

5-ASA is an effective maintenance therapy; a satisfactory response was achieved in 72% of the patients after a mean time of follow-up of 10 years.

Extensive colitis, higher DUBLIN Score, lower doses of 5-ASA, need for steroid and anaemia can predict a worse prognosis at the initial diagnosis and are associated with higher therapeutic requirements. These findings may be used in our clinical practice to identify patients that might benefit from an early step-up approach and minimize the morbidity associated with uncontrolled disease.
P461 COVID-19 outcomes in patients receiving anti-TNF treatments: A systematic review and meta-analysis
Authors: Kokkotis G , Kitsou K , Xynogalas I , Spoulou V , Magiorkinis G , Poulakou G , Syrigos K , Bamias G
Published: January 2022

Background

Accumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients.

Methods

A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta-analysis were described qualitatively.

Results

In total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30–0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27–0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42–0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41–0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68–1.39, I2=20) adjusted for age, sex and comorbidities.

Conclusion

TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.