bluuebunny/crossref_metadata_2025_split huggingface dataset:
P753 Early perianal abscess recurrence in patients with perianal Crohn's disease on biologic therapy predicts long-term permanent fecal diversion
Authors: Yokoo T , Yoshikawa S , Tsutomu M , Terauchi S , Uchida H , Nakao T , Yamaoka K , Inagaki M , Tani T , Okamoto K , Inatsugi N 
Published: January 2024

Abstract

Background
Generally, it’s difficult to estimate the efficacy of biologics (Bio) for perianal lesions of Crohn’s disease (CD) and lack of evidence. Sometimes, we experience the recurrence of perianal abscess and need to perform re-drainage even after starting 1st Bio. When the 1st bio fails, choosing an accurate 2nd Bio is difficult. The most severe result of this situation is rectal amputation. We wonder if any relationships between recurrence timing and long-term outcomes exist. We reviewed and aimed to know our institute’s perianal CD (pCD) treatment.

Methods
We retrospectively investigated patients' medical charts with pCD from 1988 to 2022 at Kenseikai Nara Coloproctology Center. We excluded the patients without using Bio or starting Bio after rectal amputation. The cases with missing values are excluded, too. We defined "early" as within two years and compared two cohorts, the early recurrence group (ER) and the no or late recurrence group (non-ER). We use the Kaplan-Meier method for calculating the time to fecal diversion.

Results
Eighty patients were recruited. The mean current age is 37.5 years old, and the onset of CD is 22.6 years old. The Perianal lesion’s onset is 24.5 years old. The male is 66, and 19 smokers are included. In this part, perianal lesion means only perianal abscess and fistula. Montreal Classification is shown in TABLE1.
The Median follow-up duration was 142.5 months. We performed perianal surveillance (PS) for these patients, including EUA, Abscess Drainage, and seton placement, 3.1 times for each person. After the surgical interventions, we treat them with four Bio. After starting Bio, we experienced 33 early recurrences. We observed eight transient stoma creations, nine rectal amputations, and one anorectal cancer. Among them, we calculate the relationships between early recurrence and rectal amputation and find that early recurrence is a risk factor for permanent fecal diversion (HR 6.84 95%CI 1.48-31.7, p=0.0047 FIGURE1).
We needed to switch the Bio for 31 patients during the observational period. To know which way of switching is effective for pCD, we calculate the relationships between the practice of switching and any treatment failure. Same class switching and changing MOA are not different for any treatment failure, which means re-abscess drainage and creation of any stoma (HR 0.40 95%CI 0.10-1.57 p=0.19).

Conclusion
Perianal abscess recurrence as we need to re-incision and drainage within two years after starting Bio treatment are related to permanent fecal diversion. We must pay attention to such kinds of patients, but the types of Bio we change didn’t affect any treatment failure. Further studies are needed in this field.
P774 Less combination therapy and more fistulotomy in perianal fistulizing Crohn’s disease in the elderly
Authors: Arjafallah Goulet O , Brochard C , Atienza P , Siproudhis L , Etienney I 
Published: January 2024

Abstract

Background
Prevalence of Crohn's disease (CD) is on the rise in the elderly and perianal fistulizing lesions affect nearly one in five patients over 60. Despite the specificity of luminal disease, few studies have focused on the management of perianal fistulizing CD (pfCD) in this population. This study aimed to describe pfCD in patients operated on after the age of 60 to compare findings (presentation, management, outcome) with those obtained in younger patients operated on during the same period.

Methods
Between January 2012 and December 2022, all CD patients (known or confirmed during follow-up) aged 60 years or older undergoing a first surgical intervention for anal fistula at two medical centers were included. For each older patient, two younger patients (&lt;60 yr) operated on during the same period were matched for comparison.

Results
Among 536 patients who underwent surgery between January 2012 and December 2022, there were 30 (6%) aged ≥ 60 yr at first surgery: 17/30 (63%) reported anal fistula and CD in the same year. Among matched younger patients, 31/60 (52%) reported anal fistula more than one year after CD diagnosis. Colonic involvement was more prevalent in the older age group (70% vs 33%); ileal forms were more common in the younger age group (23% vs 3%) and complex fistulas were predominant (93%) in both age groups. Use of biologics was similar in the two groups: anti-TNF alpha therapy in 96.7% of younger patients and in 86.7% of older patients (p=0.07); other biologics in 40% of patients in both groups. However, in patients over 60, combined therapy and anti-TNF alpha optimization were less frequent (p=0.0002 and p=0.0001), as was use of immunosuppressants (33%), with a vast majority on azathioprine. Older patients had fewer surgical interventions (3 vs 4.5, p=0.008). They also had less frequent sparing surgery (30% vs 58%, p=0.01), while fistulotomy was performed more frequently (27% vs 5%, p=0.003). The rates of anal fistula closure were comparable between the two groups (60% vs 62%).

Conclusion
Synchronous diagnosis of anal fistula and CD within the first year of care is not uncommon in patients over the age of 60, which suggests CD should not be overlooked in older individuals developing an anal fistula. Although there appeared to be age-based differences in overall medical-surgical management, and patients over 60 had more comorbidities, use of biologics was similar in the two groups, and the rates of fistula closure at the end of follow-up were comparable in the two populations.
P783 Exploring the impact of JAK Inhibitors on cholesterol levels in Patients with Inflammatory Bowel Disease: A Real-World Data Analysis
Authors: Gilroy L , Wilson A 
Published: January 2024

Abstract

Background
Janus Kinase (JAK) inhibitors represent a significant therapeutic advancement for individuals with inflammatory bowel disease (IBD). Previous research indicates an increase in total cholesterol (total-c) upon the initiation of JAK therapy.1The precise mechanisms remain unclear, but studies suggest that inflammation can lower lipid levels. Therefore, by addressing inflammation through JAK therapy, there may be a subsequent elevation in lipid levels. This study seeks to evaluate the impact of initiating JAK inhibitors on total cholesterol levels in patients with IBD, utilising real-world data for analysis.

Methods
A multi-site retrospective analysis was conducted on a cohort of patients with ulcerative colitis and Crohn’s disease who had been initiated on either filgotinib, tofacitinib or upadacitinib. Statistical analysis was applied to examine alterations in total cholesterol levels (total-c) before and after the initiation of JAK inhibitor therapy.

Results
A cohort of 49 patients was identified, with pre and post total-c levels available for 33 individuals included in the analysis. Utilising paired data and the Student's t-test, we examined whether initiating a JAK inhibitor led to increased total cholesterol levels. Patients commenced on tofacitinib and upadacitinib exhibited statistically significant increases in cholesterol (p=0.016, p=0.0001). Patients in the filgotinib group, although demonstrating rises in total-c in most cases, did not reach statistical significance (p=0.21). Graph 1 demonstrates the range and spread of the results. Upadacitinib increased cholesterol levels by the most on average (0.82), compared to tofacitinib (0.64) or filgotinib (0.3). Elevated cholesterol persisted beyond 12 weeks in some patients, but long-term data for all patients was not available. Notably, only one patient initiated a statin, resulting in lipid normalisation at the next assessment. No cardiac events were identified in this cohort.

Conclusion
This analysis of real-world data underscores a potential influence of JAK inhibitors on the cholesterol profiles of individuals with inflammatory bowel disease (IBD). Gaining insights into the interplay between JAK inhibitors and lipid metabolism within the realm of IBD treatment is essential for enhancing patient care and proactively addressing potential cardiovascular risks linked to these therapeutic interventions.
1.Herrera-deGuise C, Serra-Ruiz X, Lastiri E and Borruel N (2023) JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases. Front. Med. 10:1089099. doi: 10.3389/fmed.2023.1089099
P798 Study of the concordance between the enzymatic activity of Thiopurine S-methyltransferase and polymorphisms in the TPMT gene in patients with Inflammatory Bowel Disease
Authors: Céspedes Martínez E , Robles-Alonso V , Castellote L , Bravo-Nieto D , Serra X , Herrera-De Guise C , Mayorga L , Pérez Z , Oller E , Garriga-Edo S , Casellas F , Borruel N 
Published: January 2024

Abstract

Background
Thiopurine therapy is associated with an increased risk of serious adverse events in patients with Inflammatory Bowel Disease (IBD). Thiopurine S-methyltransferase (TPMT) is the enzyme responsible for metabolism, and its determination helps identify patients at risk of toxicity. This study aims to explore the level of correspondence between the TPMT genotype and enzymatic activity (phenotype) with the objective of preventing adverse events prior to the commencement of thiopurine therapy.

Methods
Consecutive patients with IBD, Crohn’s Disease (CD) or Ulcerative Colitis (UC), were included. Genotype was conducted for the most prevalent TPMT variants (TPMT*2, TPMT*3B, TPMT*3C), TPMT enzymatic activity assessment, and quantification of 6-thioguanine nucleotide (6-TGN) levels. Adverse effects were documented, along with the administration of biologics, mesalazine, ACE inhibitors or allopurinol. The primary objective was to evaluate the concordance between TPMT genotype and phenotype. Secondary objectives included determining the prevalence of genotype and phenotype within our patient cohort, 6-TGN serum levels, the prevalence of adverse events and identifying potential pharmacological inducers of the phenotype.

Results
A total of 218 patients were included (131 with CD and 81 with UC). Thirteen patients did not initiate thiopurines, and 34.63% (71/205) had discontinued treatment. The most observed adverse events were myelotoxicity (15.12%), gastrointestinal toxicity (12.20%), and hepatic toxicity (5.37%). TPMT activity exhibited a trimodal distribution, with 87.61% (191/218) having normal activity, 11.47% having intermediate activity, and 1% having low activity. Genotypically, 90.83% (198/218) had a wild-type genotype, 8.72% (18/218) had a heterozygous genotype, and 0.5% (1/218) had a homozygous genotype. The concordance index between phenotype and genotype was calculated at 0.57. Significantly, myelotoxicity was associated with the presence of genotypic variants (p=0.004). 6-TGN levels did not correlate with TPMT activity and concurrent medications did not affect TPMT activity .

Conclusion
The proactive assessment of TPMT (phenotype or genotype) before initiating thiopurine therapy effectively mitigates the occurrence of myelotoxicity in IBD patients. Importantly, the level of concordance between TPMT activity and genotype is moderate, with genotyping serving as the more reliable approach for preselecting patients susceptible to myelotoxic reactions.
P811 Age as a Predictor of Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Retrospective Study
Authors: Shehab M , Alrashed F , Alfadhli A 
Published: January 2024

Abstract

Background
Tumor necrosis factor antagonists (anti-TNFs) are effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). Several factors have been shown to be associated with anti-TNF treatment failure. We aim to investigate the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations

Methods
This was a multicenter retrospective cohort study. Chart review was conducted by evaluating patients' charts from July 2018 until September 2023. The impact pf age on anti-drug antibodies and serum drug concentration in patients with IBD across seven hospitals was investigated. Logistic regression was performed to explore the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations (ADAbs)

Results
1093 patients were included, of which 911 (83.3%) were above the age of 16. Mean age was 30.1 years old and 574 (52.2%) were males. 461(42.2%) patients were on infliximab and 632 (57.8%) patients were on adalimumab. In patients receiving infliximab, there was a significant association between older age and increasing ADAbs levels (p =0.036). Whereas in patients on adalimumab, there was no significant relationship between older age and ADAbs levels (p=0.771). Additionally, there was a significant association between older age and decreasing infliximab serum concentration (p = 0.02). Finally, there was no significant relationship between age and adalimumab serum concentration (p = 0.54).

Conclusion
In patients receiving infliximab, anti-drug antibodies were higher in older patients. Consistent with this, serum drug concentrations were lower in older patients on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among patients receiving adalimumab.
P813 A questionnaire-based study on fatigue and associated factors in Inflammatory Bowel Disease
Authors: Jeong N , Lee H H 
Published: January 2024

Abstract

Background
Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue, and associated factors, in patients with IBD.

Methods
A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Demographic, clinical, and laboratory data were collected. Disease activity was assessed by the Mayo score or Crohn’s Disease Activity Index, as appropriate. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale

Results
Among 97 ulcerative colitis and 50 Crohn’s disease patients, the mean total MFI-K score was 59.0 ± 5.5. Age, sex, body mass index, disease duration, anemia, hypoalbuminemia, and use of steroids did not affect the total MFI-K score. The anxiety and depression scores did not correlate with the fatigue score. Moderate and high disease activity significantly increased the MFI-K general and physical fatigue subscale scores compared to remission and mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, P = 0.009), while the use of biologics significantly decreased the total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, P = 0.031). Multiple linear regression showed that fatigue was significantly increased by a history of surgery for IBD and decreased by the use of biologics.

Conclusion
The degree of fatigue in patients with IBD is high, and disease activity is the most important contributing factor.
P858 Real World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease in Children and Young Adults
Authors: Kellar A , Dolinger M , Spencer E , Dubinsky M 
Published: January 2024

Abstract

Background
There is mounting interest in dual advanced therapy (DAT), combining 2 biologics or biologics with small molecules, in patients with refractory disease or partial responders. We evaluated the real-world efficacy and safety of DAT in pediatric and young adults with IBD.

Methods
Single-center, cross-sectional cohort study, conducted between 2018-2023. Primary outcome was DAT remission (clinical (Harvey Bradshaw Index ≤ 4 or partial Mayo Score ≤ 2) and biomarker (C-reactive protein ≤ 5 mg/L and/or fecal calprotectin ≤ 250 ug/g) at first efficacy assessment (T1). Secondary outcomes included remission at T2 if intensification or de-intensification occurred at T1 and T3 remission if re-intensification performed at T2. Failures defined those not achieving remission. Adverse events, surgical and therapy outcomes as of last follow up were evaluated. Descriptive statistics summarized the data.

Results
30 patients were included [43% female, 57% CD, median age of 18.3 [15.1-19.8] years, 46% &lt;18 years, and median IBD duration of 5.2 [4.0-6.9] years at DAT start] (Table 1). Of 11 (37%) treated with TOFA + UST, 100% achieved T1 remission. Of the 10 de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT remission. Of 9 (30%) TOFA + VDZ patients, 6 (67%) achieved T1 remission and of the 3 T1 failures, 1 had colectomy, and 1 of 2 attempting VDZ intensification achieved T2 remission. All 6 with T1 remission de-intensified, but 5 (83%) failed and only 1/5 attempted re-intensification and failed. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 remission and the 1 T1 failure achieved T2 remission after VDZ intensification. The 2/4 de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved T1 DAT remission and the 1 failure achieved T2 remission after UPA intensification. The 1 who de-intensified failed at T2 but in T3 remission post re-intensification. One (3%) VDZ + OZA patient achieved T1 remission and successfully de-intensified to monotherapy OZA at T2. One TOFA + UST patient developed mild leukopenia and responded to TOFA de-intensification, and 1 developed septic arthritis on TOFA +VDZ on prednisone and resumed TOFA once resolved. At last follow-up, 14/30 (47%) patients were on DAT, 11 (37%) changed therapy, 1 of which underwent colectomy and 5 (17%) were on monotherapy (Figure 1).

Conclusion
The majority of IBD patients treated with DAT achieved clinical and biomarker remission with minimal safety events; however, de-intensification to monotherapy has limited success and supports continuing DAT in more refractory patients. Future studies are needed to guide management.
P860 Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis - a six-year follow-up study
Authors: Gros B , Ross H , Nwabueze M , Constantine-Cooke N , Derikx L A , Lyons M , O'Hare C , Noble C , Arnott I D , Jones G R , Lees C W , Plevris N 
Published: January 2024

Abstract

Background
Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years.

Methods
We performed a retrospective, observational, cohort study. All adult IBD patients who had received VDZ induction for UC/IBDU were included. Baseline phenotype and follow-up data were collected via review of electronic medical records.

Results
We included 290 patients (UC n=271 [93.4%], IBDU n=19 [6.6%]) with a median time on VDZ of 27.6 months (IQR 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. Median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ≥1 advanced therapy, steroid use at baseline; and disease extension were independent predictors for VDZ persistence (Table 1). Clinical remission (partial Mayo &lt;2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at year 1,3 and 5 respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up.

Conclusion
VDZ persistence is influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline. VDZ effectiveness is enduring with favourable long-term safety profile.
P875 Filgotinib in ulcerative colitis: early real-world multicentre UK experience
Authors: Young D , Rahmany S , Taylor D , Davis E , Campbell R , Hazel K , Sethi-Arora K , Ritchie S , Dhar A , Limdi J , Cooney R , Seenan J P , Walsh A , Cummings F 
Published: January 2024

Abstract

Background
Phase 3 RCTs recruit a carefully selected population to demonstrate efficacy which may not reflect the population treated in clinical practice. We aimed to describe the use and effectiveness of filgotinib in a large UK real-world cohort of ulcerative colitis (UC) patients.

Methods
A retrospective observational cohort evaluation was conducted across six UK IBD centres. Baseline demographic and clinical data (including risk factors for serious adverse events and prior advanced therapy exposure), clinical (Simple Clinical Colitis Activity Index or Partial Mayo score) and endoscopic activity indices, and laboratory parameters (CRP and faecal calprotectin) were collected at baseline, 8 to 12 weeks after initiation (post induction), and during maintenance (the most recent review).

Results
A total of 216 patients are included in this analysis from May 2022 to November 2023 (mean follow-up period 202 days). The median [IQR] age at filgotinib initiation was 38 [27, 50] years (eight ≥65 years), 139 (64%) were male and median disease duration was 5.3 [1.9, 11.1] years. Disease extent (n=204) was: E1: 23 (11%), E2: 78 (38%) and E3: 103 (50%). 77 (36%) patients were naïve to advanced therapy; 66 (31%), 40 (18%), 25 (11%) and 8 (4%) patients had prior exposure to 1, 2, 3 or 4 advanced therapy modes of action(s) respectively, including 17 (8%) patients with prior exposure to tofacitinib. 48 (22%) patients had at least one risk factor included in the EMA warning. Of 137 patients who had endoscopic assessment at baseline, 56 (41%) and 20 (16%) had moderate or severe disease respectively. The median baseline faecal calprotectin and CRP were 800 [464, 1800] µg/g and 4 [1, 11] mg/L respectively. 82 (49%) were on concomitant corticosteroids at baseline (n=166).
Cumulative probabilities of filgotinib persistence were 86%, 76% and 58% at 3, 6 and 12 months respectively (figure 1A). Prior exposure to multiple advanced therapies or tofacitinib did not appear to impact persistence (p=0.3 and 0.08 respectively). Reasons for filgotinib discontinuation are shown in figure 1B. There was a significant improvement in the disease activity scores in patients continuing filgotinib (figure 1C). In the cohort with prior tofacitinib exposure (11 failed to respond or lost response to tofacitinib), 7 remain on filgotinib with a median duration of 281 days.
Eight patients discontinued filgotinib due to adverse events including one episode of venous thromboembolism.

Conclusion
In a large real-world cohort of UC patients, filgotinib appears to be effective and well-tolerated.