bluuebunny/crossref_metadata_2025_split huggingface dataset:
P262 Effectiveness and safety of ustekinumab in elderly patients: Real world evidence from ENEIDA registry
Authors: Casas Deza D , Lamuela Calvo L J , Arbonés Mainar J M , Ricart E , Gisbert J P , Rivero Tirado M , Sanchez Rodríguez E , Sicilia B , Gutierrez Casbas A , Merino Ochoa O , Márquez L , Laredo de la Torre V , Martin Arranz M D , Lopez Serrano P , Riestra Menéndez S , Gonzalez Muñoza C , de Castro Parga L , Calvo Moya M , Garcia Alonso J , Esteve M , Iborra Colomino M , Dura Gil M , Barreiro de Acosta M , Lorente Poyatos R , Manceñido N , Caballo B , Calafat M , Rodríguez Lago I , Guardiola Capo J , Morales Alvarado V J , Tardillo C , Bujanda L , Muñoz Nuñez J F , Ber Nieto Y , Bermejo F , Chaparro M , Almela P , Navarro M , Domènech E , García López S 
Published: May 2021

Abstract

Background
Clinical trials and real-life studies with Ustekinumab in Crohn’s disease show its good efficacy and safety profile. However, there are hardly any data on elderly patients, who are excluded from these clinical trials. Our aim is to evaluate these variables in real-life practice.

Methods
Retrospective analysis of patients from the prospectively maintained ENEIDA registry treated with Ustekinumab for Crohn’s disease. Elderly patients were selected as those over 60 years old at the start of treatment. They were compared with 2 randomised controls from the same centre, aged less than 60 years, matched for smoking habit. The degree of comorbidity was assessed using the Charlson’s index. Clinical and biochemical activity and effectiveness were defined based on Harvey-Bradshaw index and calprotectin and CRP levels at weeks 16, 32 and 54, when available.

Results
A total of 648 patients were analysed, 212 elderly (mean age 67 [63.6;72.8] years) and 436 young (mean age 41.6 [32.6;50.0] years). No differences were observed between both groups in baseline variables except for the degree of comorbidity, higher in elderly patients (1.00 [0.00;2.00] vs 0.00 [0.00;0.00], p&lt;0.001) and previous anti-TNF use, lower in the elderly (3.44% vs 15.2%, p&lt;0.001). Baseline clinical and biochemical activity was similar in both groups.
Clinical response rate was similar in both groups at week 16 (70.5% vs 76.6%, p=0.199), week 32 (67.6% vs 70.2% p=0.104) and week 54 (74% vs 74.9%, p=0.326). Steroid-free remission and biochemical response also showed no differences throughout follow-up.
The rate of adverse effects was similar in both groups (14.2% vs 11.2%, p=0.350) except for the occurrence of de novo neoplasms, which was higher in the elderly group (0.69% vs 4.25%, p=0.003). The rate of severe infections (7.08 vs 7.34, p=1.000), the need for surgery (16.5% vs 20.0%, p=0.345) and the need for hospital admission (21.7% vs 19.0%, p=0.489) did not differ.
Persistence of UST treatment was similar in both groups (log Rank test p=0.91).

Conclusion
Ustekinumab achieved clinical response in almost three-quarters of elderly patients, similar to the younger population, with no increase in the rate of infections or other adverse effects, with the exception of de novo neoplasms.
P316 Human neutrophil elastase derived fragment of calprotectin (S100a9) is a serum biomarker (CPa9-HNE) for monitoring of anti-TNFα treatment response in Crohn’s disease
Authors: Mortensen J , Karsdal M A , Grønbæk H , Hvas C L , Dige A , Bay-Jensen A C 
Published: May 2021

Abstract

Background
In patients with inflammatory bowel disease (IBD), up to 30% do not achieve response, 66% do not achieve remission, and 40% experience loss of response to anti-TNFα treatment. In Crohn’s disease (CD), fecal calprotectin is the most widely used fecal biomarker for diagnosis and monitoring of disease activity. Fecal sampling and processing are tedious compared to serum sampling, and biomarker quantification in serum is more efficient, convenient, and also more acceptable for patients. Therefore, there is a need for a robust and reliable serum calprotectin biomarker that performs better than conventional serum biomarkers. The aim of this study was to investigate the performance of a novel serum calprotectin assay, which quantifies a specific human neutrophil elastase (HNE) generated calprotectin (S100a9) fragment (CPa9-HNE), as a measure of true neutrophil granulocyte activity, for monitoring treatment responses in patients with CD.

Methods
We included 30 CD patients with clinically active (Harvey-Bradshaw Index (HBI)≥5) luminal inflammation scheduled for anti-TNF treatment (adalimumab or infliximab). Serum samples where obtained at baseline (n=30), week 1 (n=29), week 8 (n=28), week 26 (n=15), and week 56 (n=7). CPa9-HNE (Calprotectin, S100a9, specific fragment generated by human neutrophil elastase), CRP and fecal calprotectin were quantified. Remitters (n=11) were defined as patients in clinical remission (HBI&lt;5) at week 8 with no flares at week 26 or week 56. Non-remitters (n=19) were defined by having clinical active disease (HBI≥5) at week 8 or having a flare at week 26 or week 56.

Results
Patients with severe disease activity (HBI&gt;16) had significantly elevated serum levels of CPa9-HNE compared with patients in remission (p&lt;0.05), with mild (p&lt;0.05) or moderate (p&lt;0.01) disease activity. CPa9-HNE serum levels were significantly suppressed in remitters compared with non-remitters at week 8 (p&lt;0.001), week 26 (p&lt;0.01) and week 56 (p&lt;0.05) (Figure 1). Fecal calprotectin and CRP were significantly suppressed at week 8, week 26 and week 56 compared with baseline levels for remitters and non-remitters, but there was no significant difference between remitters and non-remitters (Figure 1). Non-remitters were more likely to have high levels of CPa9-HNE at baseline (tertile 1,2 vs tertile 3; OR: 6.8 (CI:1.22-36.5), p=0.027) and week 8 (tertile 1,2 vs tertile 3; OR: 24 (CI:2.56-279), p=0.0014).

Conclusion
CPa9-HNE is a novel non-invasive biomarker for monitoring treatment response to anti-TNFα for CD patients and may be used as a surrogate marker for assessing disease activity and to predict outcome of anti-TNFα treatment.
P326 An exploratory analysis of the impact of COVID-19 on colonoscopy procedures and new biologic treatment initiation among patients with Inflammatory Bowel Disease in the United States
Authors: Ungaro R , Chou B , Mo J , Ursos L , Twardowski R , Candela N , Colombel J F 
Published: May 2021

Abstract

Background
Patients with inflammatory bowel disease (IBD) require frequent colonoscopies to optimize disease management and treatment strategies. At the onset of the COVID-19 pandemic, many routine procedures were postponed to reduce the overall burden on healthcare systems. We characterized the impact of COVID-19 on IBD care by conducting an exploratory analysis of real-world US healthcare claims data to identify changes in treatment patterns and the number of colonoscopy procedures performed in patients with IBD during the first wave of the pandemic.

Methods
De-identified, open-source health insurance claims data, from Jan 2019 to Oct 2020, were obtained from the Symphony Health Integrated Dataverse® for US adults aged 18–80 years with IBD. Four outcome measures were used: number of colonoscopies performed; number of new biologic treatment initiations or treatment switches; number of new biologic treatment initiations or treatment switches in patients who had a colonoscopy within the previous 60 days; and rate of telehealth consultations per 1000 patients per month.

Results
During Jan–Dec 2019 and Jan–Oct 2020, 1.54 million and 1.29 million patients with IBD, respectively, were included. The bimonthly number of colonoscopies remained stable throughout 2019, with a maximum change of +5.4% in Jul–Aug (N = 49947) vs Jan–Feb 2019 (N = 47399). Colonoscopy use decreased by 4.7% in Jan–Feb 2020 (N = 45167) vs the same period in 2019. In Mar–Apr 2020, colonoscopy numbers decreased by 55.3% (N = 20191) vs Jan–Feb 2020 (Figure 1a); a reduction of 59.4% vs Mar–Apr 2019 (N = 49780). In May–Jun 2020 (−23.8%) and Jul–Aug 2020 (+2.0%) the difference vs Jan–Feb 2020 gradually decreased (Figure 1a). Bimonthly numbers of new treatment initiations or treatment switches in 2019 varied by up to 6.9% vs Jan–Feb 2019. In May–Jun 2020, numbers of new treatment initiations or treatment switches decreased by 17.0% (N = 10072) vs Jan–Feb 2020 (N = 12133) (Figure 1b); a decrease of 19.3% vs May–Jun 2019 (N = 12488). The number of new treatment initiations or treatment switches in patients who had a colonoscopy within the previous 60 days decreased by 42.5% (N = 892) in Mar–Apr 2020 vs Jan–Feb 2020 (N = 1551) (Figure 1c); a decrease of 44.2% vs Mar–Apr 2019 (N = 1599). Telehealth utilization increased in March 2020 and remained higher than in 2019 up to October 2020 (Figure 2).

Conclusion
Reduction in colonoscopies and subsequent initiation/switching of treatments during the COVID-19 pandemic first wave suggests lost opportunities for therapy optimization that may have an impact on longer-term patient outcomes. Increased utilization of telehealth services may have helped address gaps in routine clinical care.
P340 Real-world treatment patterns and recurrence rates of rectovaginal fistulas in patients with Crohn’s disease: A retrospective cohort database analysis
Authors: Karki C , Latremouille-Viau D , Gilaberte I , Hantsbarger G , Romdhani H , Lightner A 
Published: May 2021

Abstract

Background
Rectovaginal fistulas (RVF) are a difficult to treat perianal complication of Crohn’s disease (CD) with a significant impact on quality of life. Management of RVF includes both medical and surgical interventions. Few studies have assessed real-world treatment patterns for CD-related RVF. This retrospective US cohort database analysis aimed to assess the rate of, and time to RVF episodes of care in CD, and describe treatment patterns.

Methods
IBM Truven Health MarketScan® databases (Commercial and Medicare supplemental administrative claims [01/01/01 to 31/12/19]) were used. Adult females with a diagnosis code for CD, ≥1 medical claim with a RVF-specific diagnosis/procedure ICD-9/10 code on or after the date of first observed CD diagnosis, and ≥180 and ≥720 days of continuous health plan enrolment before and after index (date of first RVF-related code after first CD diagnosis date), respectively, were included. Treatment patterns were assessed during the 6 months pre-index (baseline period) and any time post-index. The first RVF episode of care (episode) started on the date of the first RVF-related code after CD diagnosis. RVF-related codes ≤90 days apart were considered as the same episode. Time to subsequent episodes was assessed by Kaplan–Meier (KM) analysis. Only descriptive statistics were reported for the proportion of patients with episodes and subsequent treatment patterns.

Results
Of 274 096 adult females diagnosed with CD during a continuous eligibility period, 2540 (0.9%) had a RVF-specific code. Overall, 963 patients met the inclusion criteria (median age: 46.0 years). The median follow-up (time between the index date and end of continuous health plan enrolment or data availability) was 48.5 months. During the follow-up period, 963 (100%), 430 (44.7%) and 217 (22.5%) patients had at least one, two or three episodes, respectively. KM analysis showed the probability of having a subsequent episode within 1, 2 and 5 years of their first or second episode (Figure). During the baseline period, 775 (80.5%) and 287 (29.8%) patients received non-biologic or biologic therapies, respectively, and 929 (96.5%) and 494 (51.3%) at any time post-index. At any time post-index, 587 (61.0%) patients had ≥1 RVF-related surgery.

Conclusion
This study showed patients with CD-related RVF required recurrent episodes of medical and surgical care in a US real-world setting. In addition, post-index, an important proportion of patients were observed with biologics use (&gt;50%) and nearly two-thirds of patients had RVF-related surgery. Patients with CD-related RVF had varied treatment patterns and more studies are needed to inform the standard of care for patients with RVF.
Sponsor: Takeda Pharmaceuticals, Inc.
P366 Vedolizumab maintenance therapy reduced use of corticosteroids in patients with Crohn’s disease in the GEMINI 2 trial
Authors: D’Haens G , Candela N , Uddin S , Peterson T , Dubinsky M , Colombel J F 
Published: May 2021

Abstract

Background
Corticosteroids (CSs) can induce clinical remission of Crohn’s disease (CD), but long-term use is associated with serious side effects. In the GEMINI 2 trial, a greater proportion of patients with moderately to severely active CD treated with vedolizumab (VDZ) maintenance therapy achieved CS-free remission at week 52 compared with placebo (PBO).1 Response to VDZ is influenced by prior exposure to anti-TNF therapy. In this post hoc exploratory analysis of GEMINI 2, we investigated the impact of VDZ maintenance therapy on use of CSs stratified by prior anti-TNF therapy failure status and baseline disease activity (moderate or severe).

Methods
In GEMINI 2, patients who responded to VDZ induction therapy at week 6 were re-randomized to receive VDZ or PBO every 4 or 8 weeks and began a prespecified CS tapering regimen (Figure 1).1 In patients receiving CSs at baseline, we measured change in CS dose from baseline to week 52 , proportion of patients with CS dose ≤ 7.5 mg/day, and proportion of patients with ≥ 90 or ≥ 180 consecutive CS-free days at week 52. Analyses were conducted overall and stratified by prior anti-TNF therapy failure status, baseline Crohn’s Disease Activity Index (CDAI) score (moderate: ≤ 330, severe: &gt; 330), and the composite of both measures.

Results
In the overall population, a greater proportion of patients treated with VDZ (67.7%) vs PBO (61.5%) had their CS dose reduced from baseline. This trend was also observed among patients with no prior anti-TNF therapy failure, with a baseline CDAI score ≤ 330, and with no prior anti-TNF therapy failure and a baseline CDAI score ≤ 330 (Figure 2). Similarly, numerically higher proportions of patients treated with VDZ vs PBO received a CS dose of ≤ 7.5 mg/day in the overall population and in subgroups with no prior anti-TNF therapy failure, with baseline CDAI score ≤ 330, and with no prior anti-TNF therapy failure and a baseline CDAI score ≤ 330 (Figure 3). Overall, 35.2% and 32.7% of patients receiving VDZ had ≥ 90 and ≥ 180 consecutive CS-free days, respectively, compared with 28.0% and 22.0% of those receiving PBO. The proportion of patients with ≥ 180 consecutive CS-free days was numerically higher for the VDZ group vs the PBO group, regardless of prior anti-TNF therapy failure status or baseline CDAI score.

Conclusion
VDZ maintenance therapy was associated with more successful CS withdrawal than PBO, particularly in patients with no prior anti-TNF therapy failure and moderate disease activity. Interpretation of these results is limited by the exploratory nature of the analyses, small sample sizes and different initiation weeks for CS tapering per patient.

Reference
P413 Characteristics of the stricture, not the ongoing treatment, influence the outcome of endoscopic dilatation in recurrent Crohn’s disease
Authors: Ladrón Abia P , Alonso N , Beltrán B , Minguez A , Sáez-González E , Pons-Beltrán V , Nos P , Iborra M 
Published: May 2021

Abstract

Background
Endoscopic balloon dilatation (EBD) is a conservative alternative for the treatment of post-surgical anastomotic strictures in Crohn’s disease (CD) that improves obstructive symptoms and could delay or avoid further surgeries. However, the usefulness of this technique and predictors of efficacy have been poorly evaluated in a homogeneous cohort.

Aim
to evaluate the efficacy of EBD in CD patients with anastomotic strictures as well as to analyze therapeutic success factors and the rate of adverse events.

Methods
Observational study in a tertiary hospital of a cohort of patients with diagnosis of CD who underwent EBD for anastomotic stricture after previous surgery and with obstructive symptoms. Clinical, demographic and disease characteristics, treatment used, surgery data, inflammatory parameters at time of dilatation, number of dilatations, complications and needed for subsequent surgery were analyzed. Technical success was defined when the endoscope was passed through the stricture after procedure. Therapeutic success per patient was considered when patient did not need surgery at the end of the follow-up.

Results
63 EBD were performed in 32 patients. Figure 1 shows the clinical and demographic characteristics of the patients. The diameters of the balloons used were 12-15 mm and 15-18 mm. Of the 63 examinations performed, 63.5% (n=40) showed technical success. The therapeutic success per patient was 62.5% (n=20) at 6 years of mean follow-up. Twelve patients required new surgery. The visualized neoileon after EBD had no significant recurrence (Rutgeerts i0-i2a) in 80% of dilatations. The adverse event rate was 3.1% (n=2) a microperforation and a major bleeding, both patients with Rutgeerts i4. The stricture length was the only predictor of technical and therapeutic success. Strictures with more than 40 mm of length were associated with poor efficacy. Neither the type of surgical anastomosis, current treatment, inflammatory parameters levels or balloon diameter were predictors of therapeutic success.

Conclusion
EBD appears to be a safe and effective technique that could avoid further surgery in up to two thirds of anastomotic strictures in CD in long-term recurrent CD. Longer stricture length and the presence of severe recurrence were associated with poor response and complications.
P444 Fecal calprotectin response to anti-tumor necrosis factor alpha induction and maintenance in Pediatric Inflammatory Bowel Disease
Authors: Matar M , Levi R , Zvuloni M , Shamir R , Assa A 
Published: May 2021

Abstract

Background
Fecal calprotectin (FC) is a sensitive surrogate marker of mucosal inflammation in inflammatory bowel disease (IBD). Our aim was to asses the effect of anti-tumor necrosis factor alpha (TNFα) induction and maintenance therapy on FC levels in children with IBD.

Methods
The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 were reviewed retrospectively. We identified 63 patients who had FC levels measured prior to anti TNFα induction with sequential measurements during the first months of therapy. The main outcome measures were time to FC response according to cut-offs of 250,150,100 and 50µgr/gr. Variables affecting FC response were analyzed using multivariate analysis.

Results
Out of 63 patients, mean age 13.6 (±3) years, females 28(44.4%),54 (85.7%) had Crohn’s disease. The median (interquartile range) FC at baseline was 715 µgr/gr (312–1700). The outcomes of &lt;250, &lt;150, &lt;100 and &lt;50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%) patients, respectively. The mean time (± standard error) for achieving these cut-offs were 4.8 ±0.8, 7.9±1.3, 10±1.8 and 18.5±7.2 months, respectively. There was no statistically significant correlation between age, gender, type of disease, Paris classification, extra-intestinal manifestation, albumin levels, erythrocyte sedimentation rate, C-reactive protein and the pediatric disease activity indexes at baseline and FC response. Furthermore, there was no statistically significant correlation between anti TNFα trough concentration during induction and FC response.

Conclusion
In pediatric patients with IBD, FC response (&lt;250µgr/gr) was achieved by the majority of patients within a relatively short period of time. Nevertheless, calprotectin normalization (&lt;100µgr/gr) required an average period of approximately one year in responders.
P464 Steroid dependency in patients with Ulcerative Colitis treated with advanced therapies in a German real-world-setting
Authors: Bokemeyer B , Picker N , Wilke T , Rosin L , Patel H 
Published: May 2021

Abstract

Background
An important treatment goal in Ulcerative Colitis (UC) is a long-lasting corticosteroid (CS)-free remission. Avoidance of steroid dependency in these patients is essential as chronic CS use is known to be associated with an increased risk for multiple severe adverse events.
This study aimed to identify CS dependency in patients with moderate to severe UC treated with advanced therapies.

Methods
This German claims data analysis includes adult patients with ≥2 outpatient diagnoses and/or one inpatient diagnosis for UC (ICD-10: K51) in whom an advanced therapy (anti-TNF agent, vedolizumab or tofacitinib) was initiated between 01/01/2015–30/06/2019.
CS dependency was indicated by ≥2 prescriptions of systemic CS and/or oral budesonide within a median follow-up of 23.4 months. Prior CS use was evaluated by outpatient prescriptions observed in a 12-months baseline period.
Costs were assessed until the end of the study period or loss to follow-up considering all-cause expenses for inpatient and outpatient visits, and approximated indirect cost related to sick-leave days.
Exceeding the recommended dose in maintenance therapy by more than 150% was rated as an escalation of therapy. Time to the therapy discontinuation, escalation or first UC-related hospitalization from start of index therapy were estimated using Kaplan-Meier analysis.

Results
Of 574 included UC patients with a new advanced therapy, 252 (43.9%) received ≥2 prescriptions of CS while on treatment with advanced agents in the observation period up to 24 months. Altogether, 496 patients (86.4%) had prior experience with CS in the 12-months baseline-period. Among patients with ≥2 CS prescriptions, 47.0% had switched their index therapy to another advanced agent after 24 months (31.2% without CS dependency). Median time to therapy discontinuation was 17.3 months in CS-dependent patients; and 19.3 months in those without CS dependency (p = 0.639). There were no differences between naïve or advanced therapy experienced patients, but with clearly more discontinuations in patients with previously more than 1 advanced therapy (p&lt;0.001). CS-dependent patients were more likely to require dose escalation/UC-related hospitalization within the first two years after treatment start (26.7% vs. 16.1%; p = 0.018/ 44.1% vs. 26.6%; p = 0.048; Figure 1). Total cost per patient-year was significantly higher in patients with than without CS dependency (40,884 € vs. 37,449 €; p &lt; 0.001).

Conclusion
Most UC patients starting new advanced therapies were previously treated with CS, and more than two-fifths continue to be CS dependent even after starting such a therapy. More effective therapies are needed to achieve CS-free remission.