bluuebunny/crossref_metadata_2025_split huggingface dataset:
P633 Choice of first biologic in moderate to severe ulcerative colitis – a decision analysis using time-on-treatment and UK costs
Authors: Dhar A , Wilson A , Reid V , Clark T , Tibbatts C , Dallongeville A , Robertson J , Eaton J , Cranmer H , Owen G 
Published: January 2023

Abstract

Background
Vedolizumab and anti-TNFα drugs are biologics that are used to treat moderate to severe ulcerative colitis (UC). In the UK, the decision of which drug to use at first-line is often based on a combination of clinical factors and the price of the drug (based on the one-year cost analysis from the NICE appraisal). The cost of the treatment pathway is rarely considered. Therefore, we investigated whether the choice of first-line biologic affects time-on-treatment and the overall treatment pathway costs by creating a cost model for vedolizumab followed by an anti-TNFα (VDZ–anti-TNFα) compared to anti-TNFα followed by vedolizumab (anti-TNFα–VDZ).

Methods
A targeted literature search identified 19 studies reporting time-on-treatment data for vedolizumab or anti-TNFαs in UC. We pooled data into four categories: 1) vedolizumab in people who were biologic-naïve (VDZ-1L), 2) anti-TNFα in people who were biologic-naïve (anti-TNFα-1L), 3) vedolizumab after first-line anti-TNFα (VDZ-2L) and 4) anti-TNFα after first-line vedolizumab (anti-TNFα-2L). We then fitted parametric curves to inform time-on-treatment estimates for each category. We calculated ‘direct’ treatment costs by considering drug acquisition, drug administration, dose escalation, concomitant use of immunomodulators and drug monitoring; all costs were sourced from four NHS hospital trusts (cost year 2022). As the duration of the anti-TNFα–VDZ pathway was shorter in duration than VDZ–anti-TNFα (62- vs 44-months), we modelled third line options in the shorter pathway using a weighted basket approach. Third line options included colectomy, tofacitinib, ustekinumab or dose escalation of second-line biologic.

Results
Over the 62-month time horizon (duration of the longer VDZ–anti-TNFα pathway), pathway costs per patient were similar: £41,439 for VDZ–anti-TNFα and £48,027 for anti-TNFα–VDZ (or £8,021 per year and £9,295 per year, respectively). The model predicted that using vedolizumab first-line delayed the time to costly third-line therapies compared to first-line anti-TNFα. This delay resulted from the pooled time-on-treatment data: VDZ-1L median time-on-treatment 43-months (n=585 people) and anti-TNFα-2L 19-months (n=47); anti-TNFα-1L 17-months (n=7690) and VDZ-2L 27-months (n=549).

Conclusion
When viewed over a longer period and considering all associated direct costs, a biologic treatment pathway that begins with first-line vedolizumab is not more expensive than one beginning with first-line anti-TNFα in treating moderate to severe UC in the UK. The model shows that considering the longer-term costs of a treatment pathway can give a different result compared to considering the short-term costs of single therapies alone.
P642 Network meta-analysis: efficacy and safety of treatments for fistulising Crohn’s disease
Authors: Chahal J , Sriranganathan D , Poo S , Lo S W , Kashkooli S , Garg M , Segal J P 
Published: January 2023

Abstract

Background
Fistulas are a debilitating complication of Crohn’s disease (CD) and treatment options remain limited, with sub-optimal efficacy. It is essential that other treatment options are considered, and there is a lack of head-to-head comparisons between them making positioning treatments challenging. To our knowledge this is the first network meta-analysis to help position all treatments for fistulising CD.

Methods
MEDLINE, EMBASE, EMBASE classic, the Cochrane central registry and Cochrane Specialised Trial Register were searched between 1978 and 2022 for randomised controlled trials (RCTs) reporting on treatments for fistulising CD. The primary outcomes were the efficacy of medical therapies at achieving fistula remission and maintenance of fistula closure. A network meta-analysis was performed using the frequentist model with pooled relative risks and P scores used to rank treatments, in accordance to PRISMA guidelines [Figure 1].

Results
964 studies were identified with the search criteria, with 28 RCTs after screening included for analysis with a total of 2,239 patients. At the 8 – 12 week end-point, none of the interventions were statistically significant, with tacrolimus ranked first at 4 times better than placebo (RR, 4.56; 95% CI, 0.76 – 27.30) at inducing remission of fistulas [Figure 2]. At the 16 – 24 week time point, infliximab produced the only statistically significant result with the 5mg/kg dose proving most effective (RR, 2.30; 95% CI, 1.40 – 3.77) [Figure 3]. At 44 weeks ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24 – 4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06 – 3.99) and infliximab 5mg/kg (RR, 1.68; 95% CI, 1.03 – 2.75) also producing a statistically significant result [Figure 4]. A limitation of this network meta-analysis is the significant heterogeneity between studies and variations in end-point definition, with certain small numbers in certain intervention groups limiting generalisability.

Conclusion
Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising CD, other biologics such as ustekinumab and adalimumab may have a role. Future RCTs with standardised end-points are needed to further investigate biologics, especially ustekinumab and adalimumab, head-to-head against infliximab in the treatment of fistulising CD.
P651 Comparison of Adverse Events of SARS-CoV-2 Vaccination between Patients with Inflammatory Bowel Disease and Healthcare Workers
Authors: Kim J , Sagong M , Lee Y J , Kim K O , Kim E S , Kim E Y , Jang B I 
Published: January 2023

Abstract

Background
This study aimed to investigate the adverse events (AEs) after SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) and to compare them with healthcare workers (HCWs).

Methods
We conducted a web-based survey on the local and systemic AEs experienced within 7 days of SARS-CoV-2 vaccination (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19) in IBD patients and HCWs between October 2021 and February 2022. The frequency of all AEs was compared between IBD patients and HCWs, and propensity score matching method was used to control confounding factors.

Results
A total of 336 IBD patients (139 Crohn’s disease [CD] and 197 ulcerative colitis [UC]) and 288 HCWs who completed the questionnaire had received the same type of vaccine for their first and second doses. Common local AEs in patients with IBD were injection site pain (78.9% and 70.8% after receiving first and second vaccine doses, respectively), swelling (35.4% and 31.5%), and induration (35.1% and 26.5%), and systemic AEs were fatigue (44.6% and 42.0%), myalgia (42.6% and 37.2%), and fever or febrile sense (29.5% and 32.1%). All severe AEs were rarely observed (0-3.9%). Hospital visits or hospitalizations associated with AEs were observed in 16 (4.8%) and 18 (5.4%) patients, respectively. A small number of patients reported deterioration of bowel frequency (CD: 10.1% and 12.2%, UC: 8.1% and 11.7%), abdominal pain (CD: 5.0% and 7.9%), and rectal bleeding (UC: 5.1% and 7.6%). About 30% of IBD patients reported a worsening of their sense of well-being. After propensity score matching, there was no significant increase in the frequency of AEs in IBD patients except for diarrhea (14.5% vs 4.8%, P = 0.005) and dyspepsia (15.2% vs 5.5%, P= 0.007) after first vaccination.

Conclusion
SARS-CoV-2 vaccination in patients with IBD was generally well-tolerated and severe AEs occurred rarely. Compared with HCWs, the frequency of AEs does not seem to increase except for diarrhea and dyspepsia.
P659 Continuing or stopping 5-aminosalicylate in patients with Inflammatory Bowel Disease under anti-TNF therapy: A nationwide population-based study
Authors: Seo J , Kim S , Song S , Shin S H , Park S , Hong S W , Hwang S W , Park S H , Yang D H , Byeon J S , Myung S J , Yang S K , Kim Y J , Ye B D 
Published: January 2023

Abstract

Background
The clinical impact of continuing or stopping 5-aminosalicylate (5-ASA) after escalating to treatment with an anti-tumour necrosis factor (TNF) agent in patients with inflammatory bowel disease (IBD) is currently unclear. We aimed to compare the outcomes of IBD patients who stopped or continued 5-ASA after starting anti-TNF therapy.

Methods
We analysed data obtained from the Korean National Health Insurance claims database between 2007 and 2020. Our analysis included IBD patients already on 5-ASA treatment who started anti-TNF treatment. We compared the prognosis of patients who stopped 5-ASA within 90 days of anti-TNF initiation with those who continued 5-ASA. The primary outcome was any adverse clinical event defined as a composite of intestinal surgery, IBD-related hospitalization, or new corticosteroid use. Kaplan-Meier method and Cox proportional hazards models at landmark time were used to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

Results
Among 62,262 patients diagnosed with IBD during the study period, 7,442 patients were included for analysis. A total of 1,037 (13.9%) patients discontinued 5-ASA within 90 days of starting anti-TNF therapy (Figure 1). Among the included patients, 4,479 (60.2%) had Crohn’s disease, while 2,963 (39.8%) had ulcerative colitis (Table 1). Discontinuation of 5-ASA was not associated with an increased risk of any adverse clinical events, as well as its component outcomes of intestinal surgery, IBD-related hospitalization, and corticosteroid use, with aHRs of 1.011 (95% CI, 0.934 to 1.095), 0.954 (95% CI 0.760 to 1.198), 0.995 (95% CI 0.894 to 1.107), and 0.969 (95% CI, 0.890 to 1.056), respectively (Table 2). In addition, the cumulative incidence of each adverse clinical event, as well as the composite outcome, were not significantly different between the two groups (all, p &gt; 0.05) (Figure 2). Subgroup analysis by sex, IBD type, the timeframe of anti-TNF use, pre-anti-TNF 5-ASA use duration, pre-anti-TNF corticosteroid use, pre-anti-TNF hospitalizations, pre-anti-TNF emergency department visits, and anti-TNF agent type also showed no significant difference in the development of adverse clinical events between the two groups.

Conclusion
In this nationwide population-based study, we observed that discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse clinical events.
P661 Clinical response over 24 weeks for initial and delayed responders to induction therapy with risankizumab in Crohn’s disease: data from the ADVANCE and MOTIVATE studies
Authors: Panaccione R , Dotan I , Ferrante M , Danese S , Bossuyt P , Kligys K , Neimark E , Zambrano J , Liao X , D’Haens G 
Published: January 2023

Abstract

Background
The efficacy and safety of risankizumab (RZB) in patients with Crohn’s disease (CD) has been demonstrated.1,2 We reported that an additional 12 weeks (ie, induction period 2) of RZB therapy could induce clinical response in patients with CD who did not achieve clinical response after an initial 12-week induction period.3 In this post hoc analysis, we report the proportion of patients who achieved clinical response over 24 weeks (initial and delayed responders to RZB induction therapy).

Methods
Data were pooled from the ADVANCE and MOTIVATE phase 3 RZB studies. Patients who had not achieved stool frequency (SF)/abdominal pain score (APS) clinical response (≥ 30% decrease in average daily SF and/or ≥ 30% decrease in average daily APS and both not worse than baseline) after an initial 12-week induction with intravenous (IV) RZB (600 mg or 1200 mg) at weeks 0, 4, and 8 were rerandomized 1:1:1 in induction period 2 to receive IV RZB 1200 mg (at weeks 12, 16, and 20) or subcutaneous (SC) RZB (180 mg or 360 mg at weeks 12 and 20) in a double-dummy–blinded fashion. In this post hoc analysis, efficacy was analysed in patients treated with either 600 mg RZB IV or placebo (PBO) for 12 weeks in the PBO-controlled induction period and patients who did not achieve clinical response with 600 mg RZB IV for 12 weeks and were rerandomized to 360 mg RZB SC every 8 weeks during induction period 2 (currently marketed RZB doses). SF/APS clinical response was assessed at week 12 for initial responders and at week 24 for delayed responders in induction period 2. Non-responder imputation with no special data handling for data missing due to COVID-19 was used. No multiplicity adjustment was performed.

Results
Of the 889 patients randomised to 600 mg IV RZB or PBO in the induction studies, 70.0% (369/527) in the RZB group compared with 45.6% (165/362) in the PBO group achieved SF/APS clinical response at week 12. Of the 47 patients who did not achieve initial clinical response to 600 mg IV RZB and received 360 mg SC in induction period 2, 32 (68.1%) achieved delayed SF/APS clinical response at week 24. The proportion of patients achieving SF/APS clinical response over 24 weeks (either initial or delayed responders) was 89.1% (401/450). The safety profile of RZB in patients with CD has been reported.1,2

Conclusion
In patients with moderate-to-severe CD, RZB treatment leads to approximately 9 of 10 patients achieving either initial (600 mg IV) or delayed (600 mg IV followed by 360 mg SC) clinical response over 24 weeks.
References:
1. D’Haens G, et al. Lancet. 2022; 399: 2015-30.
2. Ferrante M, Panaccione R, et al. Lancet. 2022; 399: 2031-46.
3. D’Haens G, et al. United European Gastroenterol J. 2021; 9(S8): 96-7.
P668 Differential efficacy of biologic agents for Inflammatory Bowel Disease Unclassified and comparison with Ulcerative Colitis: a propensity score analysis of 4054 patients from the UK IBD BioResource
Authors: Kapizioni C , Desoki R , Balendran K , Lam D , Shawky R , Pele L , Parkes M , Raine T 
Published: January 2023

Abstract

Background
Data on efficacy of biologic drugs in Inflammatory Bowel Diseases Unclassified (IBDU) are lacking as these patients are commonly excluded from randomised controlled trials. In addition, real world data on the use of biologic agents in IBDU are scarce. We explored the effectiveness of first line biologic therapy in patients with IBDU and compared between drugs and with outcomes for patients with Ulcerative Colitis (UC) in the UK IBD BioResource.

Methods
Demographic, disease, treatment and outcome data were retrieved from the UK IBD BioResource, capturing &gt;36,000 subjects across &gt;100 UK centres. Treatment failure was assessed according to persistence on therapy with clinician assessment of treatment success, without the need for treatment change or surgery. Dose-escalation was not considered indicative of treatment failure. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. We compared Kaplan Meier curves for treatment survival using log rank test.

Results
In total, 198 and 3856 evaluable patients with IBDU and UC respectively received first line biologic therapy and were included in the analysis. Median follow up was 2.6 years (IQR 1.1-4.6). In the IBDU group, 104 were female (52.5%), median age at diagnosis was 28 years (IQR 19.7-42) and median disease duration was 10.4 years (IQR 6.7-15.7). The majority of IBDU patients used infliximab (n=143), while the rest used adalimumab (n=42) and vedolizumab (n=13) with no difference in biologic therapy persistence before and after adjustment (before IPTW adjustment, log rank p = 0.062; after IPTW, log rank p = 0.135, Figure 1). No difference was found in biologic therapy persistence between patients with IBDU and UC (before IPTW adjustment, log rank p = 0.581; after IPTW, log rank p = 0.438, Figure 2).

Conclusion
Outcomes for patients with IBDU receiving first line biologic therapy were similar for those observed in patients with UC. This should lend confidence to patients and physicians using biologic therapy for this under-investigated condition. For patients with IBDU, although persistence on vedolizumab was numerically better than for anti-TNFs, this difference did not reach significance and the vedolizumab sample was small. Adalimumab and infliximab appeared to offer similar efficacy for patients with IBDU.
P680 A real-life experience of Crohn’s Disease Exclusion Diet use at disease onset and as an add-on therapy in pediatric Crohn’s disease
Authors: Scarallo L , Fioretti L , Pochesci S , Pierattini V , Banci E , De Blasi A , Di Paola M , Lionetti P 
Published: January 2023

Abstract

Background
We aimed at appraising real-life efficacy of Crohn’s Disease Exclusion Diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics in a tertiary-level center. We also aimed at identifying early responders to this dietary regimen.

Methods
We gathered clinical, anthropometric and laboratory data of patients aged less then 18 years of age with a diagnosis of CD, who were consecutively treated with CDED coupled with PEN as main treatment for the induction of remission or in the setting of loss of response to other therapies. We collected data of patients who received CDED plus PEN from April 2019 to June 2022 at diagnosis, at the beginning of the dietary treatment, and at the phase 1. Patients who interrupted diet during follow-up were considered as treatment failures on an intent to treat basis. We compared groups using chi-square, Fisher’s exact test, Mann-Whitney U or related-samples Wilcoxon signed rank tests or McNemar’s test as appropriate.

Results
47 patients were retrospectively identified. Table 1. summarizes clinical and biochemical characteristics at diagnosis and at CDED with PEN initiation. 24 (51.1%) patients started CDED as induction therapy at disease onset, whereas 23 (48.9%) of them received CDED with PEN as add-on therapy. 32/47 (68%) patients achieved clinical remission (wPCDAI &lt; 12.5) at the end of phase 1, 16/24 patients (66.7%) who started CDED as induction therapy and 16/23 (69.5%) of those who started CDED as add-on, with no statistically significant difference among the two groups (p=1.00). Laboratory parameters significantly improved in both groups (Figure 1.). There were no statistically significant differences in clinical remission rates between patients with mild-to-moderate and severe disease at the end of phase 1 (25/35 vs 7/12, p=0.481). At disease onset, 14 patients added a concomitant treatment (11 patients added anti-TNF alpha, 3 patients added IMM and one patient added anti-TNF alpha + IMM) after a median time of 4 weeks (IQR: 3-5 weeks). 28 patients had clinical data gathered at week 3. Patients who achieved clinical response at week 3 (a change in wPCDAI &gt; 12.5) were more likely to be in clinical remission at the end of phase 1 (17/20 vs 1/8, p&lt;0.01), both in patients who started CDED at disease onset and in the add-on setting.

Conclusion
CDED with PEN confirmed its efficacy in a real-life setting, both as induction regimen and as add-on therapy, also in patients with clinically severe disease. Early clinical response predicts clinical remission at the end of phase 1, possibly allowing identification of dietary responsive disease.

Table 1.

Figure 1.
P689 Predictive transcriptional signatures associated to vedolizumab therapy response in patients with ulcerative colitis
Authors: Camba Gómez M , Arosa L , Calviño-Suárez C , Bastón-Rey I , Ferreiro-Iglesias R , Porto M , Nieto L , Domínguez-Muñoz J E , Barreiro-de Acosta M , Conde-Aranda J 
Published: January 2023

Abstract

Background
Vedolizumab is one of the current treatments for patients with inflammatory bowel disease (IBD). The efficacy and safety, along with its gut specificity, make this drug an appealing therapeutic option for IBD patients with moderate to severe disease. However, as observed for other biologic treatments, a significant proportion of patients do not have an initial response to vedolizumab treatment. Currently, there is a lack of reliable predictive tools for vedolizumab treatment response, although this would help to alleviate the socioeconomic costs derived from this disease. For that reason, the primary aim of this study is to show putative transcriptional signatures associated with vedolizumab treatment response.

Methods
For the realization of this study, we used RNA-seq datasets from the Gene Expression Omnibus (GEO) database: GSE191328. This dataset includes samples from peripheral blood cells from responder and non-responder ulcerative colitis (UC) patients treated with vedolizumab and infliximab at baseline. Gene Set Enrichment Analysis (GSEA) was performed to compare the differential expression and the enrichment analysis was calculated using ssGSEA of the different groups under study.

Results
The analysis of the transcriptome of peripheral blood cells from responder (R) and non-responder (NR) vedolizumab-treated patients at baseline revealed interesting enrichment results. We found 20 gene sets positively enriched in NR versus R and only 9 gene sets negatively enriched in the same phenotypes. In order to find vedolizumab specific transcriptional signatures, we performed a similar analysis in samples from infliximab-treated patients. After that second round of analysis, we observed that around 50% of the enriched gene sets were similar for both biological treatments. Nevertheless, several interesting biological functions such as peroxisome function, reactive oxygen function or beta-catenin signalling are specifically enriched in NR patients to vedolizumab treatment.

Conclusion
Our data suggest that vedolizumab NR patients specifically show a transcriptional enrichment profile, which differs from vedolizumab R patients. Also, the comparative analysis with infliximab-treated patients reveals that those specific transcripts are modulated in response to this α4β7 integrin antibodies in peripheral blood cells. Therefore, we found a solid system to search for vedolizumab therapy predictive response markers using low invasive techniques.