bluuebunny/crossref_metadata_2025_split huggingface dataset:
P468 Association of uncontrolled disease with quality of life and healthcare resource utilisation in Ulcerative Colitis patients treated with advanced therapy in the United States
Authors: Igho-Osagie E , Knight H , Barlow S , Harvey N , Khandker R 
Published: January 2023

Abstract

Background
Advanced therapies (AT; i.e., biologics, biosimilars, Janus kinase inhibitors) are used to treat patients with moderate to severe ulcerative colitis (UC) after inadequate response to conventional treatments; yet some patients continue to have uncontrolled disease. We examined the association between uncontrolled UC and health-related quality of life (HRQoL) and healthcare resource utilisation (HCRU) in a real-world clinical setting.

Methods
The analysis was conducted using secondary data from the Adelphi UC Disease Specific Programme™,1 a cross-sectional, retrospective survey of gastroenterologists and patients, from January 2020-March 2021. Gastroenterologists provided clinical characteristics and HCRU information for 5-7 consecutive UC patients, while EuroQol-5-dimensions (EQ-5D), EQ-visual analogue scale (EQ-VAS), short inflammatory bowel disease questionnaire (SIBDQ) and work productivity and impairment questionnaire (WPAI) were patient-administered to capture HRQoL status. Patients receiving AT for ≥6 weeks were classified as uncontrolled if: physician assessment was currently moderate or severe, they had ≥2 flares in the last 12 months, or currently had ≥3 symptoms. Patient characteristics and outcomes were compared using T-test and Fisher’s exact test. Multivariable linear regressions estimating the association between UC control status and HRQoL were adjusted for age, ethnicity, disease duration and severity at diagnosis.

Results
Of the 236 patients included in the sample, 57.6% had uncontrolled disease and were likely to be non-White (27.9% v 14.0% controlled; p=0.01). Although healthcare provider consultations were similar in both groups, uncontrolled patients had more radiological imaging (mean 1.9 v 1.3, p&lt;0.01), endoscopies (mean 0.6 v 0.3, p&lt;0.01) and hospitalisations (mean 0.2 v 0.1, p=0.01) in the last 12 months compared to controlled patients. Uncontrolled patients reported significantly lower (worse) total and subdomain SIBDQ scores (total: 47.2 v 59.6; systemic symptoms: 4.8 v 5.9; bowel symptoms: 4.7 v 6.1; emotional function: 4.6 v 5.6; social function: 4.8 v 6.2; all p&lt;0.01; Table 3). EQ-5D (0.85 v 0.92, p&lt;0.01), EQ-VAS scores (76.3 v 86.1, p&lt;0.01) and activity impairment (29.2 v 16.7, p&lt;0.01) were significantly worse in the uncontrolled group.

Conclusion
A substantial number of UC patients continue to have uncontrolled disease and high unmet need despite AT use. These patients experience poorer HRQoL and contribute a significant burden on healthcare resources. Study findings highlight the need for innovative therapeutic options that would further reduce disease burden for patients and the healthcare system.
1. Anderson P et al. Curr Med Res Opin 2008;24;3063–72.
P473 Corticosteroid-free clinical remission rates with guselkumab maintenance therapy in patients with moderately to severely active Crohn’s disease: Week 48 analyses from the phase 2 GALAXI 1 study
Authors: D’Haens G , Afzali A , Filip R , Rolim A , Terry N A , Salese L , Sahoo A , Frustaci M E , Yang Z , Andrews J M , Danese S , Hisamatsu T 
Published: January 2023

Abstract

Background
Corticosteroids are often used in Crohn’s disease (CD) to control inflammation. However, they are associated with adverse events; thus, achieving and maintaining remission without corticosteroids is a major treatment goal. GALAXI 1, a phase 2b, double-blind, placebo (PBO)-controlled study, evaluated efficacy and safety of guselkumab (GUS), a selective interleukin-23p19 subunit antagonist, in patients (pts) with moderately to severely active CD. Primary efficacy and safety data were presented previously. Here, we report corticosteroid-free clinical remission rates through Week (Wk) 48.

Methods
Pts with moderately to severely active CD were randomised in a treat-through design to GUS 200, 600, 1200mg; ustekinumab (UST) ~6mg/kg; or PBO intravenous (IV) induction followed by maintenance dosing (GUS 200mg IV--&gt;GUS 100mg subcutaneous [SC] every 8 weeks [q8w], GUS 600mg IV--&gt;GUS 200mg SC q4w, GUS 1200mg IV--&gt;GUS 200mg SC q4w, UST ~6mg/kg IV--&gt;UST 90mg SC q8w, PBO nonresponders--&gt;UST ~6mg/kg IV--&gt;UST 90mg SC q8w, PBO responders--&gt;PBO SC q4w). Corticosteroid tapering was mandatory from Wk12 if medically feasible. Efficacy endpoints included corticosteroid-free CD Activity Index (CDAI) clinical remission (&lt;150) and pt-reported outcome (PRO)-2 remission at Wk48 in the primary efficacy population. Pts randomised to PBO were not included in Wk48 efficacy analyses. GALAXI 1 was not powered to evaluate efficacy differences between treatment groups at Wk48; UST was a reference arm. Analyses were prespecified but not multiplicity controlled.

Results
At Wk48, 55.7-71.4% of pts in the GUS dose groups achieved corticosteroid-free CDAI clinical remission (Table 1). Similar rates were observed when the corticosteroid-free duration was ≥30 or ≥90 days before Wk48. Among pooled pts in CDAI clinical remission at Wk48 in the GUS groups, 115/120 (95.8%) were corticosteroid free. At Wk48, 49.2-68.3% of pts in the GUS dose groups achieved corticosteroid-free PRO-2 remission (Table 1). Among pooled pts in PRO-2 remission at Wk48 in the GUS groups, 105/110 (95.5%) were corticosteroid free. Outcomes in the reference UST group are shown in Table 1. Among pts in the GUS dose groups, 30.2-39.3% were using corticosteroids at Wk0 (median prednisone equivalent dose 20.0mg/d in each group); at Wk48, 60.0-78.9% of these pts met corticosteroid-free criteria (Table 2).

Conclusion
High rates of corticosteroid-free CDAI clinical and PRO-2 remission were achieved at Wk48 in the GUS dose groups. Among pts in clinical remission, most were corticosteroid free. Nearly all pts maintained corticosteroid-free CDAI clinical remission for ≥90 days. GUS IV induction followed by SC maintenance therapy also effectively reduced corticosteroid use at Wk48.
P500 Real life 2 year experience with ustekinumab in a Spanish open-label cohort of ulcerative colitis patients.
Authors: Iborra Colomino M I , Ferreiro-Iglesias R , Martín-Arranz M D , Mesonero-Gismero F , Mínguez A , Porto Silva S , García-Ramírez L , García de la Filia I , Bastida G , Nieto García L , Suárez Ferrer C , Aguas M , Barreiro de Acosta M , Nos P 
Published: January 2023

Abstract

Background
Ustekinumab has been recently approved for the treatment of moderately to severe ulcerative colitis (UC). Data from the UNIFI clinical trial are encouraging; nevertheless, real-world assessment is needed. We assess the effectiveness, safety and pharmacokinetics of ustekinumab in a cohort of refractory UC patients.

Methods
Multicentre and observational study of UC patients who received ustekinumab for active disease. Values for Partial Mayo Score (PMS), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8, 24 and 52 weeks and at 18 and 24 months when was possible. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalizations were documented. Possible predictors of response were examined.

Results
One hundred and eight patients were analyzed (Table 1).

Two patients only received the first IV dose. During follow-up, 58 patients (54%) required interval reduction (every 4 weeks (76%) and every 6 weeks (24%)) after a median of 22.3 weeks [11.6, 41.2]. Intravenous reinduction doses were administered to 20 (18.5%) after 27.7 weeks [6.64, 56.3]. Three patients required a maintenance therapy with IV administration. The clinical remission (PMS≤ 2) rates were 39.6%, 41%, 51% at 8, 24 and 52 weeks, respectively, and 61%, and 57.7% at 18 and 24 months, respectively. FC levels returned to normal (&lt;250 μg/g) in the 39.6%, 41%, 51%, 61%, 58% of the patients at weeks 8, 24 and 52 and at 18 and 24 months respectively. CRP returned to normal (&lt;3 mg/L) in the 79%, 75%, 76.5%, 71% and 70% of the patients at weeks 8, 24 and 52 and at 18 and 24 months respectively. PMS, FC and CRP values and ustekinumab through levels over time are shown in Figure.

Fewer previous anti-TNF agents and the loss of response to anti-TNF were associated with clinical response and with normalization of FC respectively. No variables at baseline (body mass index, serum albumin, and lymphocytes count) were associated with ustekinumab through levels. Of the 17 patients with endoscopy before and after treatment, 6 were in remission and 3 with mild activity. The AEs were recorded in 5 (4.6%) patients, 12 (11%) were hospitalized and 9 (8.3%) had surgery. A total of 23 patients (21%) discontinued ustekinumab over time, the persistence rates were 98%, 91%, 83% and 81% at 8, 24, 48 and 96 weeks respectively.

Conclusion
This is the first study to show the real-world long-term effectiveness, persistence, endoscopic improvement and safety of ustekinumab in a cohort of highly refractory UC patients. The clinical remission preceded the FC normalization. Ustekinumab through levels and their pharmacokinetic require further investigations.
P523 Quality, safety and equity of care outcomes for inflammatory bowel disease patients at four tertiary referral centres in Australia using a cloud based management system Crohn’s Colitis Care (CCCare): A real world observational study.
Authors: Cheema M , Narouz I , Pipicella J , Garden F , Lynch K , Andrews J , Ghaly S , Connor S 
Published: January 2023

Abstract

Background
Inflammatory bowel disease (IBD) is a global problem and Australia has amongst the highest prevalence rates. This study looked to assess the quality, safety and equity of care across four specialised IBD centres in Australia over a 12-month period using the cloud-based IBD clinical management system called Crohn’s Colitis Care (CCCare). This study aimed to define existing care at each centre and the range of performance across each centre to propose potential benchmarks for optimal quality IBD care.

Methods
The study was conducted across four tertiary IBD centres in Australia (Centres A, B, and C were public hospitals and D was a private centre). De-identified data within the backend CCCare research registry was audited between 1st of July 2021 to 31st August 2022. People with IBD who had a clinical assessment documented within the platform during this 12-month period were included.
We assessed quality of IBD care using disease activity based on patient reported outcome measures (PROMs), biomarkers and endoscopy; surgery rates; health maintenance indicators including vaccination and skin cancer screening rates and; key performance indicators including steroid use, smoking rates and current opioid use. Safety of care was assessed using adverse events from therapy and hospital admission due to therapeutic complications. Equity of care examined education levels and ethnicity.

Results
A total of 1889 patients were included. 63% had Crohn’s disease and 37% had ulcerative colitis. 51% of the cohort was female. The median age was 39 years (IQR 30-53) and the median disease duration was 8.4 years (IQR 3.3-15.7) (Table 1). Current steroid use was between 6% to 15.4%. Faecal calprotectin (FCP) remission rates (250μg/mg) were between 65-84% and patient reported outcome (PRO-2) remission rates were between 76-88% with the highest rates observed at Centre D (Figure 1). 74 patients underwent a surgical procedure. COVID-19 vaccination rates were between 40.1% to 88.8% with the highest rates once again observed at Centre D. 3% of the cohort was documented as currently using opioid medications. 12.2% were recorded as currently smoking at Centre A compared to 2.6% at Centre D. 55 medication related adverse events were recorded and 94 patients had a hospital admission during the study period.

Conclusion
This study showcases how CCCare can readily provide researchers with granular, real-world data to audit the quality of IBD care at 4 specialised centres in Australia over a 12-month period. While there were some differences (higher vaccination rates, lower smoking and steroid use rates at Centre D), quality and safety of care was still fairly uniform across the various sites and can serve as a standard of care for IBD patients in Australia.
P529 Year-two follow-up results of an observational study conducted in Crohn’s disease and ulcerative colitis patients treated with infliximab biosimilar CT-P13 in a real-life setting
Authors: Laharie D , Pierron G , Brault Y , Bouhnik Y , Nancey S 
Published: January 2023

Abstract

Background
ReFLECT study has been carried out to investigate real life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Aims: describe the profile of inflammatory bowel disease (IBD) patients (pts) treated with CT-P13 in a real-world setting and the treatment durability over time.

Methods
ReFLECT is a multicentre, prospective, observational study conducted in France. Eligible pts were IFX naive pts (IFX-N) starting CT-P13 and those who have been switched from infliximab originator to CT-P13 (IFX-S). Treatment maintenance was described indirectly and expressed as the percentage of pts without treatment failure during the 2 years of follow-up; treatment failure was defined as a permanent discontinuation of CT-P13 due to lack or loss of response and/or intolerance or death. Two years of follow-up final results of adult IBD pts using descriptive statistical analyses, are presented here.

Results
Among the 1400 adult pts included from Oct 2016 to April 2019, 751 had an IBD and 649 had a rheumatic disease; 530 pts with Crohn’s disease (CD; 51.5% females; mean age±SD: 38.1±13.9 years old; 327 IFX-N / 188 IFX-S) and 221 with ulcerative colitis (UC; 44.8% females; 43.5±17.3 years old; 152 IFX-N / 59 IFX-S), with a median disease duration since diagnosis of 7.5 and 6.2 years respectively. Nearly 80% of pts were already under CT-P13 before inclusion, and 35.3% of CD and 32.6% of UC pts had a concomitant treatment with AZA. At first CT-P13 administration, 54.3% of CD pts had an HBI&gt;4 and 60.6% of UC pts had a Mayo score&gt;6 in IFX-N pts compared with, 15.8% and 23.1% in IFX-S pts respectively. From first administration of CT-P13 to 24 months of follow-up, a higher proportion of pts without treatment failure was observed in IFX-S than in IFX-N pts: 83.7% [95%CI:78.0;89.9] vs 65.7% [58.6;73.7] in CD and 91.2% [81.7;100.0] vs 53.4% [43.0;66.2] in UC pts respectively (Figures 1 and 2). Main reason for CT-P13 withdrawing was treatment failure in IFX-N and IFX-S: 14.7% and 7.4% of CD, 21.7% and 5.1% of UC pts respectively. Withdrawing for intolerance involved 9.2% and 7.4% of CD, 7.2% and 3.4% of UC naive and switched pts respectively. Regarding safety (Table 1), 51.3% CD pts and 45.2% UC pts reported at least one adverse event (AE). AEs with suspected relationship with CT-P13 were described in 18.5% and 17.6% and serious AEs in 13.2% and 12.7% of CD and UC pts respectively. AEs were balanced between IFX-N and IFX-S.

Conclusion
2 year follow-up data indicate that CT-P13 induce effective therapeutic maintenance in pts with CD and UC receiving IFX for the first time, and maintain a sustained disease control in pts having switched from IFX originator to CT-P13. This real-life study did not highlight any new safety concerns.
P533 Relation between TL1A expression in intestinal mucosa, and endoscopic severity and clinical course in ulcerative colitis
Authors: Shimodaira Y , Yoshida T , Watanabe K , Takahashi S , Fukuda S , Koizumi S , Matsuhashi T , Iijima K 
Published: January 2023

Abstract

Background
TL1A is a TNF super family member cytokine encoded by TNFSF15 and reported to be a disease susceptibility gene for IBD. The relationship between TL1A expression and IBD pathophysiology, clinical course, endoscopic findings was not sufficiently clear. The aim of this study was to clarify the correlation between TL1A expression in the intestinal mucosa of UC and endoscopic severity, clinical severity, and clinical course.

Methods
The subjects were patients with UC who were visiting our hospital. Mucosal samples were biopsied from rectum with lower gastrointestinal endoscopy, and TL1A gene expression was examined by RT-PCR. We analyzed the relationship between patients’ background, clinical symptoms, blood test findings, and mucosal activity and TL1A expression.

Results
A total of 77 specimens obtained with individual colonoscopy from 61 cases were included. Median age was 43, 36 cases were males, duration of disease was 2 years, the number of pancolitis was 54, median partial mayo score (pMayo) was 3, and the level of CRP was 1.5 mg/L. The number with Mayo endoscopic subscore (MES) of 0, 1, 2, and 3 were 14, 27, 24, and 12, respectively, and the mean TL1A expression was 1.76-, 1.09-, and 1.17-times higher in MES 1, 2, and 3 than in MES 0, respectively. TL1A expression was significantly higher in MES 1 than in MES 0 and MES 2. TL1A expression was significantly lower in the active group (pMayo 4 or higher) compared to the clinically low disease activity group (pMayo 3 or lower). TL1A expression was significantly lower with CRP ≥0.03 compared to CRP &lt;0.03. TL1A expression was significantly higher in those with MES 1 at the initial onset than in those with MES 2 and 3. Eight cases were compared before and after induction therapy, and TL1A expression increased 1.9-fold after induction therapy. No correlation was found between the use of biologics and small molecular compounds and the expression of TL1A.

Conclusion
Relatively low activity in UC revealed higher mucosal expression of TL1A. TL1A is known to be secreted from various cell types such as macrophages and lymphocytes. It was suggested that the source of cell types and the amount of expression would alter according to the degree of inflammation.
P555 Systematic review with meta-analysis: The impact of cancer treatments on the disease activity of inflammatory bowel diseases
Authors: Grimsdottir S , Attauabi M , Dahl E K , Burisch J , Seidelin J B 
Published: January 2023

Abstract

Background
The association between cancer treatments and exacerbation of IBD is unclear. We aimed to evaluate the effects of cancer treatments on the disease activity of IBD.

Methods
We performed a systematic review of the literature on cancer therapy in patients with pre-existing IBD. Electronic searches of PubMed, Cochrane Library, and Embase were combined with manual searches (September 2021). Meta-analysis was performed using the random-effects model. The primary outcome was flares of IBD following cancer therapy. Secondary outcomes were need for IBD-related hospitalization, surgery, and initiation or intensification of steroid or biological treatments to manage IBD flares.

Results
In total, 33 studies were included in the systematic review, comprising 1,298 patients with IBD who received cancer treatment (Figure 1). The overall occurrence of IBD flares following cancer treatment was 30% (95% confidence interval (CI) 23-37%, Figure 2). IBD flares resulted in utilization of systemic steroids and biologic therapies among 25% and 10%, respectively, and in discontinuation of cancer treatment among 8% of patients (Figures 3a and 3b). Finally, risk of gastrointestinal toxicity following immune check point inhibitor treatment (ICI) was increased in patients with IBD compared to patients without IBD (RR=3.62, 95% CI 2.89-4.78) (Figure 4). Despite this, the studies generally reported that flares were manageable.

FIGURE 1. Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flow diagram summarizing study selection.

FIGURE 2: Forest plot of incidence of IBD flares following cancer therapy, grouped by cancer treatment.

FIGURE 3: Forest plot of incidence of need for initiation of a) systemic steroids or b) initiation or intensification of biologic therapyfor managing IBD flares following cancer treatment.

FIGURE 4: Forest plot of risk ratios of GI toxicities following cancer treamtment in patients with IBD vs patients without IBD.

Conclusion
Current data indicate a high proportion of patients with IBD experiencing a flare following the start of cancer treatment. Patients with IBD were at increased risk of gastrointestinal toxicity following ICI treatment compared to those without IBD. However, cancer therapy-induced IBD flares were manageable and should not preclude appropriate cancer treatments.
P560 Curcumin-QingDai combination for patients with active ulcerative colitis: A randomized double-blinded placebo-controlled trial
Authors: Ben-Horin S , Salomon N , Karampekos G , Viazis N , Lahat A , Ungar B , Eliakim R , Kriger-Sharabi O , Reiss-Mintz H , Yanai H , Dotan I , Zittan E , Maharshak N , Hirsch A , Weitman M , Mantzaris G J , Kopylov U 
Published: January 2023

Abstract

Background
The herbal extracts Curcumin and QingDai (QD, Indigo) were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC.

Methods
This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS.

Results
There were 59 patients enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized (48.8% biologics and/or immuno-modulators experienced, 36.6% biologics-experienced). The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p&lt;0.001), 50% calprotectin-reduction in 46.4% versus 15.4% (p=0.08) and endoscopic improvement in 75% versus 20% (p=0.036), in the CurQD and placebo groups, respectively. The overall rate of adverse events was comparable between the groups. Among week-8 responders to CurQD, additional 8 weeks of treatment with curcumin alone resulted in 93%, 80% and 40% with maintained clinical response, clinical remission and clinical-biomarker response, respectively, at week 16. CurQD treatment uniquely resulted in activation of the AhR pathway, as gauged by a signficantly up-regulated expression of CYP1A1 in the rectal mucosa, which was not observed among patients receiving placebo, 5ASA or biologic drugs.

Conclusion
In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC