bluuebunny/crossref_metadata_2025_split huggingface dataset:
P539 Patient Preferences for Inflammatory Bowel Disease Treatments: Development of a European Preference Survey using a Discrete Choice Experiment
Authors: Schoefs E , Vermeire S , Ferrante M , Sabino J , Verstockt B , Avedano L , De Rocchis M S , Sajak-Szczerba M , Saldaña R , Straetemans N , Vandebroek M , Huys I , Janssens R 
Published: January 2023

Abstract

Background
There is a growing consensus across stakeholders on the value of patient preference (PP) studies, as recognized by the European Medicines Agency and the European Network for Health Technology Assessment. This study aimed to develop a PP survey to quantitatively evaluate which characteristics are most important to inflammatory bowel disease (IBD) patients, so that the results can inform the medicinal product life cycle (MPLC).

Methods
Following the PREFER recommendations, a four-step approach was followed to develop the PP survey: 1) stated preference method selection, 2) attribute and level development, 3) survey implementation, and 4) survey piloting. Throughout the different steps of the survey development, an advisory board (AB) consisting out of patients, patient organizations, gastroenterologists, IBD nurses, and statisticians were consulted.

Results
First, a discrete choice experiment (DCE) was chosen as the preferred elicitation method because it allows to reach the objectives of the survey, namely to: 1) quantify the relative importance of different attributes, 2) elicit the trade-offs patients make, and 3) measure preference heterogeneity. Second, a scoping literature review of IBD clinical trials, available IBD treatments, and previously published preference studies was performed. Discussions on these characteristics with patients (n=11) during focus group discussions (FGDs) using the nominal group technique revealed the following patient prioritized characteristics: prevent surgery, long-term clinical remission, improved quality of life, occurrence of urgency, and improved labor rate. Based upon the results of the FGDs, a preliminary list of possible attributes for inclusion in the DCE was refined during AB meetings. This list was iteratively adapted until consensus was found on 14 attributes, their levels, and corresponding explanations (Figure 1).

Third, the DCE survey was designed to include these 14 attributes using partial profiles next to measures about sociodemographic variables, health literacy, and treatment experience. Fourth, piloting the study with IBD patients (n=4) revealed that the survey was comprehensible, had a good flow, and contained graphics that supported the content. Only minor text edits were needed.

Conclusion
It is key to develop a PP survey in partnership with patients and other members of the AB. This survey will be rolled out across Europe in 11 different languages and will increase understanding of which treatment aspects are most important to IBD patients. These aspects should be included in drug development and evaluation so that the MPLC can be more patient-centered and future treatments will target aspects that are most important to IBD patients themselves.
P543 Induction and maintenance of mucosal healing in Crohn’s disease with ustekinumab in clinical practice – Results of a nationwide, prospective, multicenter study in Germany (MUCUS)
Authors: Baumgart D C , Stallmach A , Schubert A , Howaldt S , von Arnim U , Ochsenkühn T , Stein J , Lügering A , Schmidt D , Schulz M , Fischer A 
Published: January 2023

Abstract

Background
Ustekinumab (UST) is a fully human IgG1k monoclonal antibody to human IL-12/23p40 approved in several jurisdictions for the treatment of adult patients with moderately to severely active Crohn’s disease (CD). UST’s impact on induction and maintenance of mucosal healing, fistula healing and extraintestinal manifestations were not fully elucidated in the registration trial program.

Methods
In this prospective, multicenter study (EudraCT number: 2017-005151-83) across all care levels in Germany, we evaluated the real-world effectiveness of UST prescribed within its German label to achieve the primary endpoint of combined clinical (Harvey Bradshaw Index (HBI) score reduction ≥ 3 points from baseline) and endoscopic (50% reduction of the simple Endoscopic Score for Crohn Disease (SES-CD) from baseline) response in week 52 and a variety of secondary endpoints including mucosal healing defined as the complete absence of mucosal ulcerations in any ileocolonic segment and endoscopic remission defined as an SES-CD score of 0 – 2.

Results
We recruited 52 CD patients (female n=28, bionaive n=13, bioexposed n=39). See Table 1 for baseline demographics and pertinent history details. At week 52, 50% (n=12/24) of patients achieved the primary endpoint [50% (n=3/6) in the bionaive, 45.5% (n=5/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively], 58.3% (n=14/24) of patients achieved endoscopic response [50% (n=3/6) in the bionaive, 54.5% (n=6/11) bioexposed to one and 71.4% (n=5/7) bioexposed to multiple biologics cohorts, respectively], 33.3% (n=8/24) of patients achieved endoscopic remission [50% (n=3/6) in the bionaive, 27.3% (n=3/11) bioexposed to one and 28.6% (n=2/7) bioexposed to multiple biologics cohorts, respectively], 45.8% (n=11/24) of patients achieved mucosal healing [50% (n=3/6) in the bionaive, 36.4% (n=4/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively]. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event (TEAE), in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to discontinuation of UST, but no very severe events or deaths (Table 2).

Conclusion
UST reliably induces endoscopic response and mucosal healing in both bionaive and bioexperienced CD patients in routine clinical practice. The limited samples size is a direct result from the Covid-19 pandemic. No new safety signals were recorded.
P549 One-Year Comparison of Clinical and Endoscopic Outcomes of Tofacitinib Versus Vedolizumab for Ulcerative Colitis After Anti-Tumor Necrosis Factor Failure: A Real-World Cohort Study in the United States
Authors: Dalal R , Sharma P , Bains K , Pruce J , Allegretti J 
Published: January 2023

Abstract

Background
Tofacitinib (tofa) is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We compared 52 week real-world outcomes of tofa vs vedolizumab (vedo) for UC after anti-TNF failure.

Methods
In this retrospective cohort study, adults initiated tofa or vedo after failure of ≥1 anti-TNF between 5/1/18 and 4/1/21 at a large U.S. medical center. Vedo patients were frequency matched to tofa patients 2:1 by age and sex. The primary outcome was steroid-free clinical remission at 12 and 52 (+/- 4) weeks (SFCR 12 and 52, simple clinical colitis activity index [SCCAI] ≤2 or provider assessment and no use of oral/IV steroids for ≥30 days). The secondary outcome was endoscopic response (ER) within 52 weeks (decrease in Mayo endoscopic subscore [MES] by ≥1 point). Other outcomes within 52 weeks: endoscopic remission (MES=0), biochemical response/remission (improvement by 25%/normalization of C-reactive protein), drug discontinuation for non-response (NR), improvement in arthralgia, UC hospitalization, and adverse events (AEs). Multivariable logistic regression was performed for primary/secondary outcomes adjusting for UC duration, number of prior anti-TNFs, steroid/immunomodulator use, albumin, Montreal disease extent &gt;E1, MES = 3, and UC hospitalization within 12 months.

Results
136 vedo patients were matched to 68 tofa patients. Tofa patients had more anti-TNF exposures, higher CRP and SCCAI, and most had prior vedolizumab exposure (Table 1). 54% of tofa vs 46% of vedo patients achieved SFCR 12 and 59% vs 45% achieved SFCR 52. Within 52 weeks, 74% tofa vs 55% vedo had ER, 30% vs 27% had endoscopic remission, 55% vs 50% had improvement in arthralgia, 71% vs 59% had biochemical response, 46% vs 32% had biochemical remission, 5% vs 13% had UC hospitalization, 30% vs 29% discontinued treatment for NR, and 0% vs 2% discontinued treatment due to AEs (vedo group only: perforated diverticulitis, nausea, and oral pain) (Figure 1). During available follow-up (not limited to 52 weeks), the most common AEs (reported among &gt;1% of total cohort) included rash (0% tofa vs 4% vedo), C. difficileinfection (1% vs 2%), shingles (2% vs 1%), COVID-19 (1% vs 2%), other infection (2% vs 4%), and elevated liver enzymes (1% vs 2%) (Figure 2). After multivariable logistic regression, tofa was associated with a non-significantly higher odds of SFCR 12 (OR 1.66, 95% CI 0.77-3.62) and significantly higher odds of SFCR 52 (OR 2.15, 95% CI 1.01-4.61) and ER within 52 weeks (aOR 3.42, 95% CI 1.08-10.80) vs vedo.

Conclusion
Tofa was associated with higher odds of SFCR 52 and ER vs vedo for UC. AEs were consistent with known safety profiles. Due to limited sample sizes, larger cohort studies are needed.
P558 Etrasimod for the treatment of ulcerative colitis: analysis of infection rates from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trials
Authors: Regueiro M , Siegmund B , Yarur A , Steinwurz F , Gecse K B , Goetsch M , Bhattacharjee A , Wu J , Green J , McDonnell A , Crosby C , Lazin K , Ferreira Branquinho D , Modesto I , Abreu M T 
Published: January 2023

Abstract

Background
Infections are an important safety concern in patients with IBD and may be due to its therapies, such as corticosteroids. Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). The biologic effect of etrasimod leads to selective and reversible lymphocyte retention in lymph nodes with a decrease in peripheral lymphocyte count. We report the infection events from the phase 3 ELEVATE programme.

Methods
Infection events were evaluated in the pivotal UC pooled safety analyses set comprising two phase 3 studies: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369). Subjects (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). We report the n (%) and exposure-adjusted incidence rate (EAIR) of infections including serious infections, severe infections, opportunistic infections (including tuberculosis), and herpes infections. Infections were considered adverse events of special interest (AESI) if they were severe (≥ CTCAE Grade 3), were opportunistic infections, or were herpes zoster or herpes simplex infections.

Results
From the pooled ELEVATE UC 12 and ELEVATE UC 52 trials, 527 subjects received ≥1 dose of etrasimod 2 mg (265.6 subject-years of exposure) and 260 subjects were randomised to PBO (103.0 subject-years of exposure). Infections were similar between treatment groups (etrasimod: 99 [18.8%], EAIR=0.41; PBO: 46 [17.7%], EAIR=0.52). The most frequent infections in both groups were COVID-19, urinary tract infections, and nasopharyngitis (Table 1). Serious infections occurred in 3 (0.6%) subjects in the etrasimod arm (EAIR=0.01) and 5 (1.9%) in PBO arm (EAIR=0.05). Two cases of herpes zoster were reported in each treatment group (etrasimod: 0.4%, EAIR&lt;0.01; PBO: 0.8%, EAIR=0.02); these were localised and nonserious. One opportunistic infection was reported in each arm (etrasimod: subject withdrew from the study on day 20, the AE of Cytomegalovirus infection [Grade 2] was reported on day 36; PBO: tuberculosis [Grade 2]). Overall, 3 cases of infection led to discontinuation: 2 in the etrasimod arm (both mild) and 1 in the PBO arm (Table 2). No subject with an absolute lymphocyte count &lt;0.2×109/L subsequently reported a serious/severe or opportunistic infection. There were no deaths.

Conclusion
In these trials, etrasimod-treated subjects reported no increase in infections relative to PBO. Serious infections and herpes zoster were more commonly reported in the PBO-treated group. Longer-term follow-up data from the ongoing 5-year open-label extension will further characterize the etrasimod safety profile.
P561 Risk of stoma formation in patients with Crohn’s perianal fistulas over a two decades period. A cohort study from a tertiary referral center.
Authors: Bislenghi G , Baldi C , Ferrante M , Sabino J , Verstockt B , Wolthuis A , Vermeire S , D'Hoore A 
Published: January 2023

Abstract

Background
Optimal management of perianal Crohn’s disease (pCD) consists of combined medical (preferentially anti-TNF) and surgical treatment. However, it is still unclear if this has improved outcomes. This study aimed to described outcome and prognosis of pCD patients at a referral center over almost two decades.

Methods
All pCD patients referred for active perianal fistulas between 2000-2018 at our center were considered eligible for this retrospective study. Patients were divided into two groups according to the date of pCD diagnosis: period A (2000-2006) and period B (2006-2018). The complement of Kaplan-Meier estimates were used to visualize the time since pCD diagnosis until temporary and definitive fecal diversion. Clinically important outcomes such as need for temporary or permanent fecal diversion, and factors associated to these outcomes were evaluated by Cox regressions models.

Results
A total of 336 patients with active pCD were identified. The mean interval between the diagnosis of CD and the perineal fistulizing disease was 4.9 years (+-7.64). Mean follow up was 10.83 years (SD ± 4.5). The two groups were similar for demographic and clinical characteristics, except for the cumulative exposure to biologicals prior to pCD diagnosis [27.8% vs 46.9% in period A and B, respectively (p&lt;0.001)]. (Table 1) The risk for temporary and definitive fecal diversion was higher for group B, at 5- [temporary stoma: 10.8 CI (6.7%-17.3%) vs 27.3% CI (21.1%-34.9%), p&lt;0.001; definitive stoma: 0.7% CI (0.1%-4.8%) vs 13.1% CI (8.7%-19.5%), p=0.002] and 10-years follow-up [temporary stoma: 23.3% CI (17%-31.5%) vs 39.0% CI (31.1%-48.1%), p&lt;0.001; definitive stoma: 11.7% CI (7.2%-18.7%) vs 19.9% CI (13.9-28.0%), p=0.002], respectively. (Figure 1 and Figure 2). At multivariate analysis, the presence of extraintestinal manifestations [HR 2.55 CI (1.40-4.62)], B2 stricturing disease [HR 4.43 CI (1.46-13.4)], B3 penetrating disease [HR 7.10 CI (2.37-21.27)], and diagnosis of pCD diagnosis after 2006 (period B) [HR 2.20 CI (1.16-4.17)], were independent risk factors for need for permanent ileostomy. (Table 2)

Conclusion
This retrospective analysis spanning almost twenty years shows that prognosis of CD patients affected by anal fistulas remains poor and has not much changed over time, despite the introduction of biologicals and new surgical techniques. The observed increase in definitive fecal diversion in more recent years can be partially explained by referral bias and/or a more aggressive clinical management of the most severe cases. Extraintestinal manifestations and synchronous complicated luminal disease increased the risk of definitive stoma in the long-term.
P562 Real world effectiveness and safety of ozanimod: One-year follow-up from a large tertiary center
Authors: Cohen N A , Choi D , Garcia N , Choi N , Picker E , Krugliak-Cleveland N , Cohen R , Dalal S , Sakuraba A , Pekow J , Rubin D 
Published: January 2023

Abstract

Background
Ozanimod is a first in class sphingosine-1-phosphate receptor modulator approved by the FDA for moderately-to-severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. We provide one-year follow up results of our patient cohort treated with ozanimod.

Methods
This prospective, observational cohort study includes consecutive patients who initiated ozanimod at our center. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical response was defined as a decrease in ≥3 points in SCCAI from baseline with only patients with clinically active disease included in the analysis, and clinical remission was defined as an SCCAI score of ≤ 2.

Results
47 patients have initiated ozanimod therapy at our center: 45 patients with ulcerative colitis (UC), 1 patient with Crohn’s colitis and 1 patient with lymphocytic colitis. Only patients with UC were included in the effectiveness analysis. Demographics are in Table 1: in the UC cohort, the mean age was 40.6 ±16.6 years, mean disease duration was 9.6 ±9.2 years, 26 (58%) were male, 23 (51%) had extensive colitis, and 34 (76%) had previous advanced therapy exposure. 19 had baseline endoscopy with a mean Mayo endoscopic score of 2.6 ±0.5. Clinical response, remission, and corticosteroid free remission (CSFR) rates at weeks 2, 4, 10, 24, and 52 are in Figure 1. At week 10, follow-up was available for 41 patients: 18 patients (55%) achieved clinical response, 24 (59%) clinical remission, and 22 (54%) achieved CSFR. At week 52, follow-up was available for 30 patients: 5 (17%) achieved clinical response, 5 (17%) clinical remission, and 4 (13%) achieved CSFR. There were no significant differences between advanced therapy naïve and experienced patients, including when stratified by the number of previous advanced therapies or prior use of vedolizumab (Figures 2A+B and 3). Patients with a &gt; 75% reduction in absolute lymphocytes had numerically greater induction clinical response and remission rates (80% vs 54%, p=0.4 and 75% vs 53%, p=0.4, respectively). 13 patients experienced adverse events (AEs): hypertension (n=2), transient nausea (n=2), fatigue (n=3), dry skin (n=2), transient liver enzyme elevation (n=2) and transient headache (n=3). Two AEs required discontinuation – hypertensive crisis in a patient with a prior dx of hypertension, and fatigue. There were no episodes of symptomatic bradycardia.

Conclusion
We present one-year real world follow-up of ozanimod in a largely treatment-refractory cohort of patients with UC, and describe modest one-year effectiveness and a safety profile that is not different from that described in the clinical trials.
P563 Monitoring of vedolizumab drug levels in a treat to target strategy for moderate-severe IBD (MOVE-IBD)
Authors: Logan H , Rimmer K , Doecke J , Patrick D 
Published: January 2023

Abstract

Background
Vedolizumab is an effective drug in moderate-severe ulcerative colitis (UC) and Crohn’s disease (CD). A previous link between drug exposure and clinical response has been suggested in the literature making therapeutic drug monitoring (TDM) for vedolizumab an attractive idea to try and optimize patient outcomes. Recent data from the ENTERPRET induction study in UC presented at Digestive Diseases 2022 suggest no advantage to dose optimizing based on vedolizumab levels. Thus, there is discordance in the literature regarding the clinical relevance of vedolizumab drug levels. We aimed to clarify the utility of proactive TDM of vedolizumab trough levels in our cohort of maintenance vedolizumab patients using objective markers of disease activity in a treat to target strategy.

Methods
A single-centre retrospective cross sectional cohort study using proactive TDM was performed on 84 patients with moderate to severe IBD on vedolizumab maintenance therapy. All patients were receiving standard vedolizumab dosing of 300 mg every eight weeks. A vedolizumab trough drug level was paired with clinical and objective markers of disease activity. The two endpoints examined were steroid free clinical remission and objective remission. Objective remission targets were individualized for each patient using a treat to target strategy and benchmarked against a baseline abnormal test. Steroid free clinical remission was defined in Crohn’s disease as a Crohn’s disease activity index (CDAI) of &lt; 150 and in ulcerative colitis as a partial MAYO score of &lt; 1 in a patient off steroids. Objective remission was defined as faecal calprotectin &lt; 150 ug/g, normal bowel wall thickness on intestinal ultrasound or magnetic resonance imaging without associated features of inflammation or absence of ulceration on colonoscopy or sigmoidoscopy within 3 months of the vedolizumab level.

Results
Median trough vedolizumab levels for patients were numerically higher but not statistically different in patients who had achieved steroid free clinical remission (13.3 ug/ml vs 8.89 ug/ml p = 0.544) or objective remission (15.22 ug/ml vs 10.28 ug/ml p = 0.139). See Figures 1. In addition, quartile analysis showed no statistically significant difference between quartiles of vedolizumab levels and clinical or objective remission (p = 0.822).

Conclusion
Trough serum vedolizumab levels in our real-life cohort of maintenance moderate severe IBD patients were not associated with clinical or objective remission. Caution should be applied to basing treatment decisions off vedolizumab maintenance levels until more data becomes available to support its routine use in clinical practice.
P564 vedolizumab versus infliximab and adalimumab in the real-world persistence in Ulcerative Colitis and Crohn’s disease – a meta-analysis
Authors: Yiu T H , Leong R , Ko Y , Pudipeddi A 
Published: January 2023

Abstract

Background
In Ulcerative Colitis (UC), vedolizumab demonstrated increased efficacy over adalimumab in the VARSITY study. However, the real-world effectiveness of vedolizumab against adalimumab, infliximab and in UC and Crohn’s disease (CD) is not well-known. Drug persistence measures the duration of time from initiation to discontinuation of a therapy, is a surrogate marker that combines therapeutic efficacy, safety, and tolerability. This meta-analysis compared drug persistence of vedolizumab versus anti TNF alpha inhibitors (TNFi) adalimumab and infliximab in UC and CD.

Methods
Systematic review and meta-analysis were conducted with observational studies identified in electronic database – EMBASE and PubMed search from inception of 2017 to July 2022 and abstracts screened from recent gastroenterology conference – Digestive disease week 2022 San Diego. 6 observational studies evaluating persistence of vedolizumab versus TNFi (infliximab and adalimumab) among participants aged &gt;18 years with diagnosis of IBD met inclusion criteria and were included.

Results
Overall, 1 year persistence of vedolizumab is 71.2% in UC and 76% in CD, significantly higher than infliximab (56.4% in UC, 53.7% in CD) and adalimumab (53.7% in UC, 55.6% in CD). (Table 1) Head-to-head comparison shows RR of 1.15 (95% CI of 1.12 – 1.19), favouring vedolizumab.
2-years persistence was pooled from 4 studies. Vedolizumab had a 2-years persistence of 66% in UC and 61% in CD, which also shows superiority to both infliximab (49.7% for UC, 59.1% for CD) and adalimumab (31.4% for UC and 56% for CD). (Table 2) Meta-analysis with head-to-head comparison continue to show a statistically significant difference in 2 years persistence of vedolizumab versus TNFi (RR of 1.12, 95% CI 1.01 – 1.25).
For UC patients, vedolizumab shows superiority over both adalimumab and infliximab with a RR of 1.41 (95% CI 1.14 – 1.74) and 1.15 (95% CI 1.06 – 1.25) respectively and RR of 1.23 (CI 1.14 – 1.33) when adalimumab and infliximab combined.
For CD, vedolizumab has a slightly higher 1-year persistence over TNFi combined (RR 1.10 95% CI 1.02 – 1.19) but fails to show any statistically significant difference from adalimumab (RR 1.07 95% CI 0.86 – 1.32) and infliximab (RR 0.55 95% CI 0.07 – 4.35) individually.
Vedolizumab has a higher 1-year persistence in bio-naïve subgroup (RR 1.14 95% CI 1.07 – 1.22) but fails to show statistically significant advantage in bio-experienced group (RR 1.04 95% CI 0.80 – 1.35) when compare with TNFi.

Conclusion
Vedolizumab achieved a higher overall 1- and 2-years persistence compared to adalimumab and infliximab in both CD and UC but mainly in bio-naïve subjects. The benefit of vedolizumab over TNFi was more evident in UC than CD.