bluuebunny/crossref_metadata_2025_split huggingface dataset:
P887 Comparative efficacy of JAK inhibitors versus vedolizumab in patients with hypoalbumineamia and Ulcerative colitis
Authors: Pearman K , Saini V , Vincent S , Rhodes S , Harvey P 
Published: January 2024

Abstract

Background
The IBD community are seeking ways to personalize medication choices for individual patients. Hypoalbumineamia is a poor prognostic marker in ulcerative colitis (UC) as a surrogate marker of disease activity. Biologic molecules are intermittently dosed using albumin binding to maintain plasma concentration, therefore in low albumin states drug clearance is accelerated. This effect is potentially less significant in regularly dosed, JAK inhibitors (JAKi).

Methods
All patients at our unit taking a JAKi were included. Patients using vedolizumab were selected for inclusion based on the nearest neighbour with respect to medication start date. Vedolizumab was chosen as a second line advanced therapy used regularly in UC. Demographic and disease characteristics were collected. Blood tests immediately prior to starting medication were collected. Outcome measure was response to treatment based based on drug continuation and clinician documentation of treatment success at 6 months.

Results
56 patients were included; 28 receiving a JAKi, 28 patients using vedolizumab. The JAKi group consisted of 8 patients receiving Filgotinib, 12 Tofacitinib and 8 Upadacitinib. Patients receiving JAKi were younger (mean age 44 years, SD 14) compared to vedolizumab (56 years, SD 20). Both were predominantly white (JAKi n=16, Vedolizumab n=22). Chronic liver disease was uncommon in both groups; JAKi n=2 (7.1%) and vedolizumab n=3 (10.7%), none of whom had cirrhosis. More hospital admissions were observed in the year prior to starting treatment in patients who received JAKi (n=16, 57.1%) compared to vedolizumab (n=9, 32%). Hypoalbuminaemia (defined as ≤30g/L) was seen in 5 patients in each group. In patients receiving JAKi 16/23 (69.7%) patients without hypoalbuminaemia responded to treatment at 6 months, compared to 3/5 (60%) with low albumin. (p=0.999). In patients receiving Vedolizumab 18/23 (78.3%) patients responded to treatment at 6 months, compared to 1/5 (20%), (p=0.026).

Conclusion
In patients with hypoalbumineamia, vedolizumab was less effective compared to normal albumin states. A similar effect was not observed in patients receiving JAKi. Numerically the efficacy of both vedolizumab and JAKi was worse in patients with hypoalbuminaemia, as would be expected given the likely reflection of increased disease severity. This data suggests that those patients requiring advanced therapy with hypalbuminaemia might respond better to a JAKi. Further research is needed to investigate this finding.
P897 The association of HLA-DQA1*05 carriage with immunogenicity to anti-tumour necrosis factor therapy and drug persistence in Asian patients with inflammatory bowel disease
Authors: Liang R , Lin H , Goh L L , Lim W C 
Published: January 2024

Abstract

Background
HLA-DQA1*05 carriage increases anti-tumour necrosis factor (TNF) immunogenicity and lowers drug persistence in European inflammatory bowel disease (IBD) patients. There is a paucity of data for Asian patients. We hypothesize that the HLA-DQA1*05 allele is present in our local IBD population and may be associated with similar clinical and pharmacokinetic outcomes as European cohorts.

Methods
A single-centre retrospective study of consecutive IBD patients on Infliximab (IFX) or Adalimumab (ADM) was performed.
HLA-DQA1*05 carriage was tested with Sanger sequencing. Serum anti-drug antibody (ADA) levels were analysed at each IFX infusion and per physician discretion for ADM. Concomitant immunomodulator (IM) therapy with Azathioprine or Methotrexate was recorded.
Primary outcome was immunogenicity to IFX or ADM, defined as ADA concentration ≥10 AU/ml at any time point. Secondary outcomes were loss of response (LOR), defined as IBD symptom-related treatment intensification, and persistence, defined as anti-TNF continuation at end of follow-up. The effects of HLA-DQA1*05 carriage on outcomes and predictors of persistence were analysed.
Results 39 patients (28 Crohn’s disease, 11 ulcerative colitis) were included (mean age 39 years, median disease duration 10 years). 24 patients had IFX as first anti-TNF agent (21 with IM, 3 as monotherapy), 7 of whom had second-line ADM with IM. 15 patients had ADM as first anti-TNF agent (13 with IM, 2 as monotherapy), 2 of whom had second-line IFX (1 with IM). 15/39 (38.5%) patients were positive for HLA-DQA1*05. 42/48 (87.5%) of anti-TNF exposures were on IM.
In HLA-DQA1*05 carriers compared to non-carriers, development of ADA (61.1% vs 47.8%, p=0.397) and LOR (42.1% vs 31.0%, p=0.433) was numerically higher but not statistically different. Persistence of first anti-TNF agent was similar between carriers and non-carriers at the end of follow-up (median 28.0 months vs 21.5 months, p=0.364) (Figure 1). ADA development was not associated with LOR (p=0.07) or persistence (p=0.29).
19/48 (39.6%) of anti-TNF exposures discontinued treatment at the end of follow-up, 13 of whom experienced LOR. 10/13 (76.9%) of patients with LOR were female. Female sex was significantly associated with anti-TNF non-persistence on univariable (OR 4.82, 95% CI 1.38-16.75, p=0.01) and multivariable logistic regression (OR 7.24, 95% CI 1.35-38.90, p=0.02), after adjusting for HLADQA1*05 carriage, presence of ADA and anti-TNF order (first versus second-line) (Table 1).

Conclusion
In Asian IBD patients, HLA-DQA1*05 carriage may not affect immunogenicity nor treatment persistence, especially with proactive therapeutic drug monitoring and concurrent IM. Female sex negatively affects persistence. Larger prospective studies are needed.
P917 Ustekinumab and immunomodulatory combination therapy is more effective than Ustekinumab monotherapy to prevent relapse in Crohn’s patients classified as low to intermediate-probability responders by UST-CDST
Authors: Song J H , Shin J , Seong G , Kong S M , Cha B , Hong J T , Kwon K S 
Published: January 2024

Abstract

Background
Ustekinumab (UST) is a monoclonal antibody that has therapeutic effects on Crohn’s disease (CD) by blocking interleukin 12 and 23. Controversy remains about the effectiveness of the combination of UST and azathioprine(AZA) and the criteria for patients who may benefit from the combination therapy. The aim of this study was to evaluate the effect of combination therapy on relapse in patients with CD and the feasibility of UST - Clinical Decision Support Tool (CDST) as a patient selection tool for combination therapy.

Methods
Patients with moderate to severe CD showed a clinical response after UST induction therapy and observed until the relapse. Kaplan-Meier analysis was performed to evaluate the efficacy of UST with AZA and to investigate the screening ability of UST-CDST for combination therapy selection.

Results
Among 35 patients, 8 (22.9%) experienced a clinical relapse during the median follow-up period of 17.0 months of UST treatment. There was no statistically significant difference in the cumulative relapse rate according to combination therapy in all enrolled patients. (6.7% vs 35%, p=0.063) The cumulative relapse rates were 8.3% in a combination therapy group, and 43.7% in UST monotherapy group among low to intermediate-probability responders according to UST-CDST, showing a statistically significant difference. (p=0.032)

Conclusion
Combination therapy with UST and AZA seems to be helpful prevent relapse, and UST-CDST may be helpful in patient selection who effective with combination therapy.
P921 Maintenance of clinical, biochemical and transmural remission in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximab
Authors: Piazza O Sed N , Maregatti M C , Pessarelli T , Viganò C , Conforti F , Noviello D , Bezzio C , Amoroso C , Molteni C , Anolli M P , Pirola L , Saibeni S , Fraquelli M , Vecchi M , Caprioli F 
Published: January 2024

Abstract

Background
Subcutaneous (SC) infliximab (IFX) effectively maintains biochemical, clinical and endoscopic remission in inflammatory bowel disease (IBD) with a comparable safety profile to intravenous (IV) formulation. Transmural healing is considered a desirable long-term treatment endpoint in IBD, especially in Crohn’s disease (CD). Whether switching from intravenous to SC-IFX effectively maintains transmural remission in IBD is still unknown.

Methods
This is a preliminary report from a prospective multicentre cohort study on IBD patients in clinical and endoscopic remission on IV-IFX treatment switched to SC-IFX. Enrolled patients were followed-up for 12 months, with fecal calprotectin (FC), C-reactive protein (CRP), infliximab trough levels and anti-drug antibodies (ADAs) measured at baseline, at 3, 6 and 12 months. Intestinal ultrasound (IUS) was performed at baseline and every six months. At month 12 a full colonoscopy was performed for mucosal healing assessment. Remission rates and safety profile were subsequently recorded. T-Test and ANOVA for mean comparisons and Kaplan-Meier estimates were used for survival curves.

Results
43 IBD patients (69% males) were enrolled, 58% with CD, of whom 52% reported a history of perianal disease. Median disease duration and IFX therapy were 6 (IQR 3-12) and 5 (IQR 2-9) years, respectively. During a median follow-up of 311 (range 122-489) days, clinical remission rate was 98% (Harvey-Bradshaw Index &lt;5 and Mayo score &lt;2). No reactivation of perianal disease was reported. FC and CRP remained stable at each time point (p&gt; 0.05). The median baseline infliximab level was 10.02 ( range 0.1- 41.84) ug/ml. Undetectable infliximab levels (&lt;1 ug/ml) and positive ADAs were found in 6 and 14 patients, respectively; at 3 months, a significant increase in infliximab levels (mean increase 27.5 ng/ml; ± 12.5 SD; p&lt; 0.001) and a progressive decrease of ADAs titer were observed, despite unchanged SC-IFX dose. At baseline, all patients had normal bowel wall thickness (i.e. ileum ≤ 3mm, colon≤4 mm) and a Limberg score ≤1at IUS; reactive lymphadenopathies were reported in 5 patients and a mild abdominal effusion in 1. No significant changes were shown during follow-up. Mild endoscopic activity was found in 2 out 30 patients who performed follow-up endoscopy. Regarding safety profile 12 mild infectious events, 2 mild cutaneous injection site reaction and 1 non-IBD related hospital admission were observed.

Conclusion
Switching from IV to SC infliximab in a selected cohort of IBD patients confirmed to be safe and effective in maintaining clinical, biochemical, and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment in this subset of patients.
P924 Function and outcomes of ileal-pouch anal anastomosis in patients with connective tissue disorders
Authors: Schabl L , Holubar S , Erozkan K , Alipouriani A , Steele S , Spivak A 
Published: January 2024

Abstract

Background
Ileal-pouch anal anastomosis (IPAA) is a widely preferred surgical intervention for patients with medically refractory ulcerative colitis, familial adenomatous polyposis, and indeterminate colitis. Concerns have been raised regarding the impact of connective tissue disorders on the outcomes of IPAA due to potential alterations in collagen metabolism. To date, there is a lack of studies assessing the feasibility, long-term viability and pouch function of IPAA in patients with connective tissue disorders. We hypothesized that the presence of a connective tissue disorder might be associated with a higher rate of pouch complications and failure.

Methods
Data were collected from a prospectively maintained pouch database and chart reviews. Patients with connective tissue disorders were propensity score matched in a 1:5 ratio with control pouch patients without connective tissue disorder. A comparative analysis of demographics, long-term complications, functional outcomes, and quality of life was conducted.

Results
A total of 19 patients with connective tissue disorders were matched to 95 control pouch patients. The postoperative diagnoses were ulcerative colitis (82.5%), indeterminate colitis (7%), constipation (5.3%), Crohn's disease (4.4%), and familial adenomatous polyposis (1%) Connective tissue disorders identified, included unspecified diffuse connective tissue disorders (26.3%), Ehlers-Danlos syndromes (15.7%), Sjogren's syndromes (15.7%), and others. Patients with connective tissue disorders were more likely to experience pouchitis (79% vs. 56%, p=0.04). Differences in rates of pouch prolapses (10.5% vs. 4.2%, p=0.26) and of pouch failure (26.3% vs. 13.7%; p=0.17) were present but failed to achieve statistical significance. Functional outcomes, and quality of life were similar in both groups.

Conclusion
IPAA remains a feasible surgical option for patients with connective tissue disorders, offering comparable functional outcomes and quality of life. Physicians treating patients with these disorders should be aware of a potentially elevated risk of pouchitis, pouch prolapse and pouch failure.
P947 medical cannabis increases appetite but not body weight in patients with inflammatory bowel diseases
Authors: Fliss Isakov N , Seidenberg C , Meiri D , Yackobovitch-Gavan M , Maharshak N , Hirsch A 
Published: January 2024

Abstract

Background
Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD.

Methods
An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment.

Results
Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P&lt;0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010).

Conclusion
Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.
P953 Establishment and Internal Validation of a Clinical Risk Score to Predict the Efficacy of Adalimumab in Crohn's Disease
Authors: Wang F , Liang J 
Published: January 2024

Abstract

Background
Adalimumab (ADA) plays a crucial role in treating Crohn's disease (CD), but not all patients benefit from it. This study aimed to analyze the factors affecting the treatment effectiveness of ADA for CD and then establish an efficacy prediction model with internal validation.

Methods
Retrospectively collected data from CD patients receiving ADA at Xijing Hospital from October 2020 to February 2023. Collect clinical data of patients and use FITC-labeled ADA to perform immunofluorescence staining on paraffin tissue sections of CD patients before ADA treatment. The data were randomly split into training and validation. Single-factor and multiple-factor logistic regression models were used to analyze the factors influencing the 12-week clinical remission of CD patients treated with ADA in the training, determining the optimal predictive model. A line chart prediction model was established and the model's discrimination and calibration were tested. Finally, the model was internally validated in the validation set.

Results
A total of 68 patients were included in the study. The clinical remission rate of CD patients treated with ADA at 12 weeks was 55.88% (38/68). The results showed that baseline endoscopic stenosis [OR=0.019, 95% confidence interval (95% CI) 0.019-0.993], disease course [OR=0.966, 95% CI 0.940-0.993], and the number of FITC-labeled ADA-positive cells [OR=1.109, 95% CI 1.025-1.201] were factors affecting the therapeutic effect of ADA in CD patients (p&lt;0.05) which used to establish the efficacy prediction model. The AUC of the prediction model in the training and validation were 0.868 (95% CI 0.769-0.977) and 0.802 (95% CI 0.604-1) (p&lt;0.05), respectively. The clinical decision curve analysis showed that the prediction model had significant clinical benefits in both the training and validation.

Conclusion
The prediction model can provide reference for clinicians to make treatment decisions.
P958 Comparison of Paediatric Patients and Young Adults with Moderately to Severely Active Crohn’s Disease Treated with Ustekinumab in the REALITI Real-World Evidence Effectiveness Study
Authors: Steiner S , Shehzad S , Adler J , Colletti R B , Strauss R , Heile J , Adedokun O , Sheahan A , Zhang R , Lo K H , Kim L , Xiao Y , Volger S 
Published: January 2024

Abstract

Background
Few approved treatment options exist for paediatric patients (pts) with Crohn’s disease (CD). Paediatric inflammatory bowel disease (IBD) medication approvals are delayed nearly 7 years after adult approvals,1 resulting in off-label use and potential for incorrect dosing. The REALITI Study evaluated the effectiveness and safety of ustekinumab (UST) in routine clinical care in paediatric pts (age 2-&lt;18) and young adults (age 18-25) with moderately to severely active CD (Short Paediatric CD activity [sPCDAI] score ≥30) using data from the ImproveCareNow (ICN) Registry.

Methods
Effectiveness data from pts with CD treated with UST were extracted from the ICN Registry between 10 January 2010 and 29 February 2020. A supplemental, retrospective chart review was conducted to collect data not in the ICN Registry. The primary endpoint was clinical remission (sPCDAI≤10) at Week (Wk) 52. All data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence interval were calculated across multiple populations. Rates of discontinuations, IBD-related hospitalizations, surgeries, and serious infections were also calculated.

Results
A total of 479 CD pts in ICN were treated with UST, including 348 paediatric pts and 131 young adults. We report an analysis of 114 paediatric pts who weighed &gt;40 kg and had a sPCDAI ≥30. All pts were treatment refractory; 99.1% had not responded to prior biologic therapies, with less than 1% biologic naïve. Results were compared to 51 ICN young adults with moderately to severely active CD, a population for which UST is approved. Clinical remission at Wk 52 was achieved in 22.8% (26/114; 95% CI: 16.1%, 31.3%) of paediatric pts vs 21.6% (11/51; 95% CI:12.5%, 34.6%) of young adults (Figure 1A). Discontinuation rates through Wk 52 were similar between paediatric pts (25.4%) and young adults (25.5%; Figure 1B).
Overall, 36.0% of paediatric pts and 21.6% of young adults had IBD-related hospitalizations. IBD-related surgery was reported in 14.0% of paediatric pts and 11.8% of young adults. Serious infections occurred in 9.6% of paediatric pts and 3.9% of young adults. Opportunistic infections occurred in 1.8% of paediatric pts and 0% of young adults. No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred in either group. No deaths were reported.

Conclusion
This study of real-world data from the ICN Registry found similar remissions rates in paediatric pts and young adults with CD treated with UST, suggesting comparable effectiveness of UST in both age groups. No new safety signals were identified. (Crowley E, et al. J Crohns Colitis. 2022 Feb 23;16(2):331-335.)
P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial
Authors: Vuitton L , Mathieu N , Ye B D , Kim D H , Jeong A L , Lee Y N , Schreiber S 
Published: January 2024

Abstract

Background
Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction.

Methods
In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing &lt;80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score &lt;150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive.

Results
There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX.

Conclusion
Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted.
1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6.
2Wong ECL et al. J Crohns Colitis 2021;15:1114–9.
3Schreiber S et al. Gastroenterology 2021;160:2340–53.