bluuebunny/crossref_metadata_2025_split huggingface dataset:
P637 Targeting mucosal healing: dose optimization of Vedolizumab in IBD patients with inadequate endoscopic response to standard dosing
Authors: Dal Buono A , Gabbiadini R , Migliorisi G , Solitano V , Canziani L , Repici A , Armuzzi A 
Published: January 2023

Abstract

Background
The GEMINI trial assessed improved clinical outcomes after an increase to 4-weekly dosing of Vedolizumab in nearly 40% of patients with insufficient response to standard 8-weekly dosing. However, later real-world data have partially questioned the efficacy of dose optimization due to the early randomization in the study design. The investigation on dose escalation efficacy of Vedolizumab in inflammatory bowel diseases (IBD) remains scarce. We aimed to explore the clinical benefit of Vedolizumab dose escalation every 4 weeks in a cohort of IBD patients with insufficient endoscopic response to the standard dosing regimen.

Methods
This is a retrospective single-center study. IBD patients, who showed persistent endoscopic activity (Mayo score ≥ 2 or SES-CD ≥7) with 8-weekly dosing Vedolizumab were included. Clinical data were retrieved from patients’ charts. Response after therapy optimization was compared to standard 8-weekley dosing through Wilcoxon signed-rank test for quantitative variables with non-normal distribution; univariate analysis of different factors impacting on therapy response was performed.

Results
A total of 52 IBD patients, 30 (57.7%) and 22 (42.3%) with ulcerative colitis and Crohn’s disease, respectively, were included. Overall, the median disease’s duration at Vedolizumab start was 12.5 month (range 3 36); 31 patients (59.6%) had been previously treated with anti-TNFs. Before Vedolizumab dose escalation 32/52 patients (61.5%) and 20/52 patients (38.5%) showed moderate (Mayo score =2; SES-CD= 7-15) and severe endoscopic activity (Mayo score =3; SES-CD ≥ 15), respectively. We observed a significant reduction of fecal calprotectin from baseline [median 133 μg/g (range 21-3800)] after Vedolizumab optimization [median 77 μg/g (range 6.0-521)] (p&lt;0.001). After Vedolizumab optimization 28/52 patients (53.8%) obtained further endoscopic response (78.6%) or remission (21.4%) (p&lt;0.001). At univariate analysis non exposure to anti-TNF and a lower disease duration at Vedolizumab start significantly correlated with endoscopic response after optimization (HR 0.28, 95%CI 0.32 – 0.76, and HR 0.32, 95%CI 0.25 – 0.66, respectively, p&lt;0.001). No adverse events were observed after dose optimization in our cohort.

Conclusion
An increase in Vedolizumab dosing frequency is a viable treatment approach for a subset of patients with insufficient endoscopic response standard 8-weekly dosing. Higher response rates might be assessed in anti-TNF naïve patients and with a lower disease duration at therapy start. Prospective studies are needed to confirm these data.
P654 Controversies in the management of anti-TNF therapy in Crohn’s disease patients. A Delphi consensus
Authors: Gonzalez Lama Y , Ricart E , Carpio D , Bastida G , Ceballos D , Ginard D , Marín-Jimenéz I , Menchén L , Muñoz F 
Published: January 2023

Abstract

Background
Over the last years significant advances have arisen in CD. New therapies with different mechanisms of action have been approved for the management of Crohn’s disease (CD). However, there is limited evidence on optimal positioning of agents as first-or second-line therapies due to the lack of head-to-head robust comparative data. Our aim was to establish feasible and practical recommendations for the management of patients with moderate to severe CD with the use of anti-tumour necrosis factor (TNF) drugs, with special focus on controversial areas.

Methods
A group of 9 expert gastroenterologists identified current relevant clinical controversies in the management of CD with anti-TNF therapies. A comprehensive literature review was performed to analyze them and a survey was launched to examine current clinical practice. This was a structured survey organized in 2 main sections that included several questions: 1) Sociodemographic and practice related questions; 2) Opinion and attitude in daily practice related to: the use of anti-TNFs, vedolizumab or ustekinumab in naïve and refractory patients, the role of HLA-DQA105, or monitoring of drug levels. An invitation to participate was emailed to a representative number of 244 IBD treating physicians all over the country. The results of the literature review and survey were discussed in a nominal group meeting, and a set of statements were proposed for a Delphi process. The participants of the survey were also invited to the Delphi. Agreement was defined if at least 70% of the participants voted ≥7 (from 1, totally disagree to 10, totally agree). For each statement, the level of evidence and grade of recommendation was established based on the Oxford Evidence Based Medicine categorization.

Results
A total of 14 statements were generated (table 1 depicts the statements and the results of the Delphi). All but two achieved required level of agreement. The statements cover the following areas: 1) use of first-line non-anti-TNF biologic therapy; 2) role of HLA-DQA1*05 in daily practice; 3) attitudes in primary nonresponse and loss of response to anti-TNF therapy due to immunogenicity; 4) ustekinumab or vedolizumab if a change of mechanism of action is considered; 5) anti-TNF drug levels monitoring during induction; 6) combined therapy with an immunomodulator and anti-TNF monotherapy.

Conclusion
This document sought to pull together the experts’ attitudes when dealing with different clinical scenarios of patients with CD on anti-TNF.
P656 Superior treatment persistence with ustekinumab in biologic-experienced luminal Crohn’s disease: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study
Authors: Chetwood J , Ko Y , Pudipeddi A , Kariyawasam V , Paramsothy S , Leong R 
Published: January 2023

Abstract

Background
Ustekinumab has been shown equivalent to adalimumab in the treatment of biologic-naïve patients with Crohn’s disease (CD) at 1 year. However the real world persistence of these medications, and particularly when used sequentially in biologic-experienced patients is unknown. Prescription data provides real-world evidence about treatment efficacy, tolerability and prescriber and patient acceptability.

Methods
Persistent of medication was analysed from the Australian Pharmaceutical Benefits Scheme (PBS) registry data 2005-2019 for luminal Crohn’s disease, using a 10% representative sample.

Results
There were 2029 patients over the 15 year period with 5618 years of patient follow up. The median age was 43 years (interquartile range (IQR): 34-58), with 891/2029 (43.9%) male. Via therapy, 915/2029 (45.1%) were on adalimumab, 722/2029 (35.6%) were on infliximab 155/2029 (7.6%) were on vedolizumab, and 237/2029 (11.7%) were on ustekinumab. Used as a first-line biologic (bio-naïve), there was no difference between any agent for persistence (p&gt;0.05). Used after first-line (bio-experienced), ustekinumab had significantly better persistence than TNFa inhibitors (TNFi) (p= 0.006) and vedolizumab (p&lt;0.001), additionally vedolizumab had poorer persistence than TNFi (p=0.028). In bio-experienced patients, ustekinumab persistence was greater than non-ustekinumab biologic agents (p= 0.0018). TNFi persistence was significantly poorer in bio-experienced vs naïve patients (p=0.042), with a non-significant trend for poorer outcomes in vedolizumab (p= 0.059), but did not differ for ustekinumab (p=0.509). Used after a TNFi agent, ustekinumab had superior persistence to an alternative TNFi agent (p=0.033). Using a propensity score matched analysis for age, immunomodulator use and line of therapy, ustekinumab had superior to persistence to non-ustekinumab agents (p=0.0044) and to TNFi (p=0.01). Multivariate predictors of loss of persistence were biologic used (adjusted hazard ratios (aHR): 0.84, p=0.001), and line of therapy (aHR: 1.16, p=0.003).

Conclusion
The PANIC cohort with real-world data of non-hierarchical prescribing of biological agents does not support the superiority of any agent in biologic-naïve luminal CD. However for biologic experienced, the persistence is greater with ustekinumab than TNFa inhibitors, and vedolizumab persistence is significantly poorest. These findings will assist in the positioning of biological therapies in luminal CD.
P706 Monitoring asymptomatic patients with Crohn's disease: the role of intestinal ultrasound
Authors: Dussias N , Melotti L , Mazzotta E , Decorato A , Vanigli N , Rizzello F , Gionchetti P 
Published: January 2023

Abstract

Background
Intestinal Ultrasound (IUS) is a non-invasive, widely available technique that can rapidly evaluate bowel wall thickness and provide direct visualization of bowel vascularisation and motility. Studies have shown high concordance between ultrasound and MR enterography and endoscopy for disease location and activity, and fewer technical difficulties associated with IUS. While more is known about the role of IUS in evaluating response to pharmacologic treatment in CD patients, data regarding the monitoring of asymptomatic patients are scarce. Our objective was to study the impact of IUS in the management of patients with CD in stable clinical remission in a real-world setting.

Methods
We conducted a retrospective, monocentric observational study in patients with CD in clinical remission (Harvey Bradshaw Index ≤ 4), not in treatment with immunomodulators/immunosuppressants, in whom annual monitoring via IUS was performed. Biochemical data including C-reactive protein (CRP) and relevant ultrasound parameters (bowel wall thickness, extension and vascularization via Limberg score) were recorded. Changes in treatment or the need for second-level diagnostic tests based on ultrasound findings were registered along with outcomes at 1 year follow-up.

Results
A total of 201 patients with CD underwent IUS at our center between March and May 2021. Of these, 86 were in clinical remission with mesalazine treatment/no treatment. In 49/86 (57%) of cases, significant ultrasound findings were reported. In 27/49 cases, ultrasound findings led to a treatment modification or a second-level diagnostic test. Specifically, 12 patients were started on a course of oral budesonide or metronidazole; of these, 6 were in remission at 1 year follow-up, 3 patients required surgery within 1 year, and 2 experienced a disease flare treated with a second course of budesonide. Of the 15 patients in which a second-level diagnostic test was performed, in 12 cases disease activity was confirmed: 6 were started on a course of budesonide or metronidazole with persistent clinical remission at 1 year, 2 were started on biologics, and 4 developed complications during the follow-up period and were referred for surgery. In the remaining 3 cases, the second level diagnostic test excluded active disease and the patients maintained clinical remission at 1 year follow-up.

Conclusion
The results of this study demonstrate how IUS can be a useful tool that can modify treatment strategies and stratify patients requiring more invasive second-level diagnostic exams, with the objective of reducing clinical relapses. Prospective, randomized studies with large cohorts are needed to confirm these findings.
P710 Changes of gut microbiome after anti-TNF-α therapy and the prediction of clinical remission in patients with active ulcerative colitis
Authors: Shin Shin S , Oh H N , Moon J M , Joo H J , Sul W J , Choi C H 
Published: January 2023

Abstract

Background
The aims of this study are to explore the changes of gut microbiome after anti-TNF-α therapy (adalimumab; ADA) and to identify biomarkers to predict clinical remission to ADA in patients with active ulcerative colitis (UC).

Methods
Fecal samples were taken before (baseline) and after ADA administration at weeks 8 and 56 in patients with active UC. Fecal bacterial taxonomic composition and diversity were investigated by 16S sequencing and analyzed by divisive amplicon denoising algorithm version 2 (DADA2) at the level of amplicon sequence variant (ASV). The table was imported into R 4.0.2 to analyze for richness, diversity, heatmap and ordination plot . The linear discriminant analysis effect size (LEfSe) was used for statistical analysis. Clinical remission was assessed using the Mayo score.

Results
260 fecal samples from 146 patients with UC administering ADA and 40 fecal samples of healthy controls (HC) were analyzed. The mean age of the participants was 44 ±14.8 years, and 60.7% were male (patients 64.9%, healthy control 42.5%). Overall communities (β-diversity) of gut microbiota in HC clearly differed from those before, after 8 weeks, and after 56 weeks of ADA treatment in patients with UC regardless of remission. The compositions of microbiota were affected by the disease severity and extent. ADA treatment significantly reduced the dissimilarity among samples in remitters at both 8 and 56 weeks, which were not observed in non-remitters. In remitters, the abundance of genus Staphylococcus was significantly decreased and genera Bifidobacterium and Dorea were significantly increased during ADA treatment period. The baseline samples of remitter at week 8 showed a higher abundance of 40 ASVs, including Sporosarcina (ASV2803), Bacteroides sp. (ASV1298, ASV1490), and Enterobacter (ASV9330, ASV9332) compared to baseline of non-remitters. Given that the 48 ASVs increased or decreased in baseline samples of remitters at week 8, the best log ratio of average relative abundance of increased ASVs/decreased ASVs to predict remission for ADA treatment was 0.07459, with 72.4% sensitivity and 84.3% specificity on the receiver operating curve (area under the curve, 0.855).

Conclusion
The composition of gut microbiota varies depending on the status of the disease and the effectiveness of the ADA treatment. Relative abundance of s fecal bacteria before treatment can be a biomarker for predicting efficacy of ADA in patients with UC.
P743 Relative association of bowel urgency improvement versus remission of stool frequency and rectal bleeding with Patient Global Rating of Severity or Change scores in moderately-to-severely active Ulcerative Colitis: An analysis from the LUCENT-1 and LUCENT-2 Phase 3 trials
Authors: Travis S , Wu J , Keohane A , Gibble T H , Hibi T 
Published: January 2023

Abstract

Background
Bowel urgency is a common and disruptive symptom of ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB).1 Information is limited on the relationships between bowel urgency clinically meaningful improvement (CMI), bowel urgency remission, SF remission or RB remission and improvement in Patient Global Rating of Severity or Change (PGRS/PGRC) scores in patients with moderately-to-severely active UC. We estimated the associations of bowel urgency CMI or bowel urgency remission with PGRS/PGRC scores while adjusting for potential confounding effects of SF remission and RB remission, using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Methods
Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (NRS; 0=no urgency to 10=worst possible urgency).2 The 6-point PGRS scale (1=none to 6=very severe) was recorded using an electronic daily diary, and the weekly scores were averaged. The 7-point PGRC scale (1=very much better to 7=very much worse) was recorded at week (W) 12 and W52.3 Other outcomes included: bowel urgency remission (Urgency NRS score=0 or 1), bowel urgency CMI (≥3-point decrease in Urgency NRS score from baseline), SF remission (Modified Mayo subscore=0 or 1 with ≥1 point decrease from baseline) and RB remission (Modified Mayo subscore=0).2 Mediation analyses were performed to separately examine the relative association of the direct effects of bowel urgency CMI or bowel urgency remission (predictors) with PGRS/PGRC scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatmentagnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at W12 and 40 (W52 of the study).

Results
At W12, improvements in PGRS and PGRC scores were primarily due to bowel urgency remission (63.5%, 56.3%), relative to SF remission (21.0%, 21.6%) and RB remission (15.5%, 22.1%; Fig.1A). Similar results were observed for bowel urgency CMI at W12 (Fig.1B). At W52, bowel urgency remission accounted for 54.7% and 79.1% of the improvements in PGRS and PGRC scores (Fig.2A). The effects of bowel urgency CMI, SF remission, and RB remission on improvement in PGRS/PGRC scores are shown in Fig. 2B.

Conclusion
Improvements in PGRS or PGRC scores were primarily due to bowel urgency remission or bowel urgency CMI relative to SF remission or RB remission. These results support that bowel urgency may influence patients’ perceptions of disease severity and change in disease activity in UC.
References:
1Dubinsky MC, et al. J Crohns Colitis. 2020;14(1):S200.
2Dubinsky MC, et al. J Patient Rep Outcomes. 2022;6(1):114.
3Rubin DT, et al. Gastroenterology. 2022;162(3):S14-5.
P753 Comparing long-term outcomes in inflammatory bowel disease patients between switch and non-switch cohorts: no differences in infliximab persistence or safety outcomes after 54 months
Authors: Suo P , Thin L , Srinivasan A , Winston J , Jeffrey A , Menon S , Ghaly S , Haifer C 
Published: January 2023

Abstract

Background
Switching patients with inflammatory bowel disease (IBD) from originator to biosimilar infliximab has been demonstrated to be non-inferior to continuing originator infliximab by several studies. However, data comparing treatment outcomes beyond 12-months across switch and non-switch cohorts specific to IBD patients remains comparatively underreported. Here we report long-term (&gt;48 weeks) treatment outcomes of the SAME study, a large-scale parallel cohort study of Australian IBD patients who underwent non-medical switching from originator to biosimilar (CT-P13) (n=204) or continued originator infliximab (n=141).

Methods
The SAME study was a multi-centre, prospective parallel cohort non-inferiority study across seven Australian hospitals over 48 weeks undertaken between May 2017 to October 2019. The data that we present here is the long-term extension study, obtained retrospectively, which sought to compare long-term infliximab persistence beyond 48 weeks across switch and non-switch cohorts. This study included five of the original seven sites, three of which switched from originator to biosimilar infliximab. The primary outcome was infliximab persistence, defined as the proportion of originator or biosimilar infliximab treated patients from the original cohort at last follow up. Secondary outcomes included disease worsening requiring infliximab dose escalation or discontinuation, rates of adverse events, and development of antibodies to infliximab (&gt;10ng/mL).

Results
Data from 263 (90 Ulcerative colitis and 173 Crohn’s disease) of 345 (76%) patients enrolled in the original SAME study were included with median follow up of 54.2 months (IQR 46.1-59.3). At last follow-up, 103 (65.5%) and 68 (64.2%) patients across the switch and non-switch cohorts (p = 0.8) remained on infliximab. There were no differences in the proportions that discontinued infliximab due to clinical or biochemical worsening of disease (21.7 v 23.6%, p = 0.72); required infliximab dose escalation (35.2 v 32.4%, p=0.8); developed antibodies to infliximab (5.3 vs 11.3%, p = 0.09) or experienced drug related adverse events (7.8 vs 8.3%, p = 0.8) between switch and non-switch cohorts, at last follow-up.

Conclusion
Long-term infliximab persistence was similar between switch and non-switch cohorts after a median of 54 months. This study represent one of the longest ‘real-world’ comparisons between switch and non-switch cohorts specific to IBD, and should provide reassurance to clinicians and patients alike.
P767 Intestinal ultrasonography predicts short term clinical remission in patients with moderate-to-severe ulcerative colitis
Authors: Zorzi F , De Cristofaro E , Abreu M T , Montesano L , Cuccagna E , Essofi S , Biancone L , Monteleone G , Calabrese E 
Published: January 2023

Abstract

Background
Intestinal ultrasonography (IUS) is a non-invasive, easily accessible and low-cost procedure to visualize the colon and determine disease activity, extent and treatment response in IBD. Our aim was to investigate whether ultrasonographic parameters predict short-term clinical remission in ulcerative colitis (UC).

Methods
Consecutive patients (pts) with moderate-to-severe UC (total Mayo score&gt;6) starting biological therapies or small molecules were included. Patients were evaluated at baseline by clinical, biochemical, endoscopic (endoscopic Mayo score), and IUS assessments. IUS, doppler and elastographic parameters assessed at baseline before starting therapy were: bowel wall thickening (BWT), echopattern, blood flow (adapted Limberg’ score), Milan Ultrasound criteria (MUC) and shear wave elastography values. The most affected colonic segment was used for all imaging assessments. Clinical remission at 3 months was defined as partial Mayo Score=0-1. Predictive factors of clinical remission at 3 months were analyzed by logistic regression. ROC curve analysis was used to identify the best cut-off of BWT in predicting clinical remission.

Results
Thirty-one UC pts were enrolled (12 males [39%]; median age: 45 years, range 18-72; median disease duration: 108 months, range 3-312). Sixteen per cent of pts had left colitis and 84% had extensive UC according to the Montreal criteria. Forty-eight per cent of pts were treated with Anti-TNFs, 39% with vedolizumab, 10% with ustekinumab and 3% with tofacitinib. At baseline, 84% of patients had moderate disease and 16% severe disease according to the total Mayo score. A lower total Mayo score and partial mayo score at baseline were predictive of clinical remission at 3 months after starting biological therapy or small molecules than endoscopic Mayo score (OR 0.58, 95% CI 0.33-0.99, p=0.03; OR 0.55, 95% CI 0.29-0.99, p=0.037; OR 0.57, 95% CI 0.16-1.93, p=0.36, respectively; Figure 1, panels A-C). A lower BWT, Limberg’ score and MUC at baseline were predictive of clinical remission at 3 months (OR 0.19, 95% CI 0.05-0.72, p=0.0023; OR 0.22, 95% CI 0.06-0.77, p=0.004; OR 0.48, 95% CI 0.21-0.83, p=0.001, respectively; Figure 1, panels D-F). The most accurate cut-off value of BWT for predicting clinical remission was &lt;6 mm with sensitivity and specificity of 70% and 82%, respectively (Figure 1, panel G).

Conclusion
IUS easily predicts early clinical remission in patients with moderate-to-severe UC after therapy.