bluuebunny/crossref_metadata_2025_split huggingface dataset:
P477 Assessment of treatment sequence and real-world outcomes in patients with Ulcerative Colitis
Authors: Chen J , Zhao Y , Liu T , Candela N , Lasch K 
Published: May 2021

Abstract

Background
Several therapies are available to manage moderately to severely active ulcerative colitis (UC); however, little is known about the impact of treatment sequence on patient outcomes. Using real-world data, we assessed the outcomes of patients treated with different UC treatment sequences in routine clinical practice in the USA with the aim of determining the optimal position of vedolizumab within the current UC treatment paradigm.

Methods
This analysis used deidentified claims and clinical data from the Optum Research Database between 2016 and 2019. Patients diagnosed with UC were identified using International Classification of Diseases, Tenth Revision codes, and UC treatments were identified using National Drug Codes. Two scenarios of treatment sequences were analysed: with (S1) or without (S2) the inclusion of immunomodulator (IM) therapy (Table).
Patients were matched on baseline age, sex and race using nearest neighbour propensity score matching. Outcomes, including colectomy-related procedure, disease flare defined as a relevant diagnostic/imaging procedure, UC-related hospitalization, UC-related laboratory test abnormality and all-cause death, were described for each of the treatment sequences (Figure 1).

Results
Of a total of 143 678 patients diagnosed with UC, 3291 were treated with vedolizumab and an IM and/or an anti-tumour necrosis factor (TNF) therapy. Patients who received vedolizumab before an IM and/or anti-TNF therapy (S1a and S2a) had better outcomes than those who received vedolizumab after one or both of these therapies, including a numerically lower rate of UC-related hospitalizations, colectomies, disease flares, UC-related laboratory test abnormalities and all-cause death (Figures 2 and 3).

Conclusion
Given the increasing number of therapies available for the management of UC, it is important to understand the impact of treatment sequence on outcomes. Clinical trial evidence suggests that patients with UC may experience better outcomes when vedolizumab is used prior to anti-TNF therapy. This observation is consistent with the findings of this analysis of real-world outcomes in patients with UC who received treatments in different sequences.
Owing to the nature of the data, the population could not be stratified by disease activity. Future work will aim to further characterize outcomes associated with different treatment sequences in patients with moderately to severely active UC and include newly available therapies.
P492 The UC Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A prospective open label pilot study
Authors: Sarbagili Shabat C , Albenberg L , Van Limbergen J , Otley A , Yaakov M , Wine E , Weiner D , Levine A 
Published: May 2021

Abstract

Background
Strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). The goal of the pilot trial was to evaluate the efficacy of a novel microbe-directed UC diet (UCD) for clinical remission, as well as use of antibiotics for dietary refractory patients as an alternative strategy for remission.

Methods
This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores &gt;10 on stable maintenance therapy. Patients failing to enter remission (PUCAI&lt;10) on diet could receive a 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention to treat (ITT) remission at week 6 with UCD.

Results
Twenty-four UCD treatment courses were given to 23 eligible children (mean age 15.3±2.9 years). Median PUCAI decreased from baseline 35 (30–40) to 12.5 (5–27.5) week 6 (P=0.001). Clinical remission with UCD alone was achieved in 9/24 (37.5%). Median calprotectin declined from baseline 818 (630.0–1880.0) to 592.0 (140.7–902.4) week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission 3 weeks later.

Conclusion
The UC Diet appears to be effective for induction of remission in children with mild to moderate UC suggesting that diet could play a role in the disease. Sequential use of UCD followed by antibiotic therapy needs to be evaluated as a microbiome targeted steroid sparing strategy.
P493 Cost-effectiveness of venous thromboembolism prophylaxis after hospitalization in patients with Inflammatory Bowel Disease
Authors: Lee K , Lim F , Colombel J F , Hur C , Faye A 
Published: May 2021

Abstract

Background
Patients with inflammatory bowel disease (IBD) have a 2- to 3-fold greater risk of venous thromboembolism (VTE) than the general population, with increased risk during hospitalization. However, recent evidence suggests that this increased risk persists post-discharge. As such, we aimed to determine the cost-effectiveness of post-discharge VTE prophylaxis among hospitalized patients with IBD.

Methods
A decision tree was used to compare inpatient prophylaxis alone versus 4 weeks of post-discharge VTE prophylaxis with rivaroxaban 10 mg/day. Our primary outcome was quality-adjusted life years (QALYs) over one year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $US), incremental cost-effectiveness ratios (ICERs), and number needed to treat (NNT) to prevent one VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses were performed to assess uncertainty within the model.

Results
Four-week post-discharge prophylaxis with rivaroxaban resulted in 1.68 higher QALYs per 1000 persons and an incremental cost of $185,778 per QALY as compared to no post-discharge prophylaxis. The NNT to prevent a single VTE was 78 individuals, while the NNT to prevent a single VTE-related death was 3190 individuals. One-way sensitivity analyses showed that higher baseline VTE risk &gt;4.5% or decreased cost of rivaroxaban ≤$280 can reduce the ICER to &lt;$100,000/QALY. Probabilistic sensitivity analyses favored post-discharge prophylaxis in 26.5% of iterations.
Abbreviations: QALY (Quality-Adjusted Life Years), ICER (Incremental Cost-Effectiveness Ratio), NNT (Number Needed to Treat), VTE (Venous Thromboembolism)
Figure. Tornado diagram showing main drivers (variables and sensitivity ranges) of the incremental cost-effectiveness ratio (ICER).

*Values represent threshold values that reduce the ICER to &lt;$100,000/QALY.
Abbreviations: VTE (Venous Thromboembolism), DVT (Deep Vein Thrombosis), PE (Pulmonary Embolism), PTS (Post-Thrombotic Syndrome), WTP (Willingness To Pay), EV (Expected Value)

Conclusion
Four weeks of post-discharge VTE prophylaxis results in higher QALYs as compared to inpatient prophylaxis alone, and can prevent one post-discharge VTE among 78 patients with IBD. As such, post-discharge VTE prophylaxis in patients with IBD should be considered in a case-by-case scenario considering VTE risk profile, costs, and patient preference.
P495 The interplay of biopsychosocial factors and quality of life in Inflammatory Bowel Diseases: a network analysis
Authors: Knödler L L , Thomann A , Karthikeyan S , Atanasova K , Bernstein C , Ebert M , Lis S , Reindl W 
Published: May 2021

Abstract

Background
Quality of life (QoL) is one of the most relevant patient-reported outcomes in the treatment of patients with inflammatory bowel diseases (IBD), but does not only depend on disease activity. We aimed to investigate the interplay of biopsychosocial factors and their associations with QoL in patients IBD by using a network analytical approach (NA).

Methods
We measured QoL and anxiety, depression, illness identity, self-esteem, loneliness, childhood trauma, and visceral sensitivity with self-report questionnaires in two independent IBD-samples (sample 1: n=209, anonymous internet survey; sample 2: n=84, outpatients with active disease before the beginning of a biologic treatment). Additionally, fatigue, haemoglobin levels and response to biologic therapy (3–6 months after the first assessment) were assessed in sample 2. We estimated regularized partial correlation networks and conducted tests of accuracy and stability of the network parameters.

Results
In both samples, QoL had the strongest associations with visceral sensitivity and the illness identity dimension engulfment, a maladaptive integration of IBD into the ‘self’. QoL was uniquely associated with depressive symptoms and fatigue was an essential factor in this link (sample 2). Depression was the most central factor in the networks. Baseline depression scores were connected to response to biologic therapy in sample 2.

Conclusion
This is the first study using NA to assess the complex interplay between biopsychosocial factors and QoL in IBD. It reveals a comparable network structure in two independent samples emphasizing the importance of depression. Visceral sensitivity and engulfment connected most strongly to QoL. Beyond depression, visceral sensitivity and illness identity may be targetable characteristics to improve QoL in personalised holistic therapy in IBD.
P528 Reducing intravenous monoclonal antibody observation times without compromising patient safety; a single-centre observational study
Authors: Rees F , Packham A , Parmar A , Hills E , Smith M , St. Clair Jones A 
Published: May 2021

Abstract

Background
Monoclonal antibodies (MAbs) are integral to manage Inflammatory Bowel Disease (IBD). At Brighton & Sussex University Hospitals, intravenous MAbs, infliximab and vedolizumab, are administered in an outpatient setting. Licensing specifies post-infusion observation times of 1 to 2 hours. This affects waiting lists and capacity, particularly pertinent during the COVID-19 pandemic.

Methods
A single-centre observation study was conducted.
Part 1
Retrospective data was collected for all infliximab and vedolizumab infusions from April to July 2019. Patients seen twice, were included once. For established infusion patients, historical reactions were recorded. Reaction incidence was established by observations, patient questioning and patient record review.
To standardise the reactions, we used the cancer Common Terminology Criteria for Adverse Events; grade 3 is ‘severe’.
Part 2
Observation time was removed from infusion 4 in April 2020. Prospective data was collected for all infliximab and vedolizumab infusions from April to December 2020. Multiple attendances were included.

Results
Part 1
130 infliximab patients (2607 infusions) and 69 vedolizumab patients (557 infusions) were reviewed.
No severe reactions were recorded. All reactions occurred during induction dosing period. Analysis showed high levels of ‘no reactions observed’ after the first 4 infliximab infusions 97.7% (+1.6%, -4.7%), and the first 3 vedolizumab infusions 96.9% (+2.3%, -8.8%).
121 hours could be saved for infliximab and 64 hours for vedolizumab. Extrapolated this equates to 740 hours per year.
Part 2
679 infliximab infusions were administered (including 12 new starters). 418 vedolizumab infusions were administered (16 new starters). No reactions were reported.
Table key: Pt – patients, Inf – infusions, MAb – monoclonal antibody, Induct – Induction, Maint – maintenance, IV – intravenous, PO – oral, NC – not collected

Conclusion
All MAb infusion reactions occurred within 3 infusions, were non-severe and managed in clinic. By removing observation periods from infusion 4, capacity increased in concordance with COVID-19 social distancing, without affecting waiting times or patient safety. Patient experience was anecdotally improved. Further data from other centres are required to prove significance.
P535 Optimising vedolizumab in treatment sequences for Crohn’s disease: Results from a simulation model using real-world evidence
Authors: Louis E , Nikolaou A , Litkiewicz M , Agboton C , Wang S , Armuzzi A 
Published: May 2021

Abstract

Background
With the availability of biologic therapies for treating Crohn’s disease (CD) there are limited data to inform optimal treatment decisions. Vedolizumab (VDZ), an anti-integrin antibody that selectively targets lymphocyte migration to the gut, was approved in 2014 for the treatment of moderate-to-severe CD. We developed a model based on real-world evidence (RWE) to examine the effect of different positioning for VDZ in CD treatment sequences on clinical outcomes.

Methods
A Markov sequential model was developed to identify the optimal position of VDZ within a sequence of CD therapies that included corticosteroids (CS), 2 biologics and best supportive care. Three sequences were compared: VDZ as first biologic (first position), second and last biologic among anti-TNFs and ustekinumab as alternate biologic treatments. To test the behaviour of the model, VDZ was also positioned before CS (Position 0, off label). Model inputs were informed using published RWE. At each position in the treatment sequence, patients achieving clinical response or remission during induction continued on maintenance; patients on maintenance could lose clinical response or remission; patients who did not achieve response during induction or lost response during maintenance (including after dose escalation) moved to the next position of the sequence after a treatment-free interval. Surgery, development of intestinal malignancy/lymphoma, and discontinuation of treatment due to serious adverse events or death could occur at each sequence position. VDZ sequences were compared and ranked based on quality-adjusted life years (QALYs), patient-reported outcomes (PRO2/3) derived from CDAI scores, or proportion of patients undergoing surgery by the end of the 10-year time horizon for model simulation. Probabilistic sensitivity analysis (PSA) evaluated the impact of model inputs uncertainty on the outcomes.

Results
For QALYs, PRO2/3, and rates of surgery, VDZ early in the treatment sequence was the optimal positioning strategy (Table). Using QALYs as the ranking criterion, VDZ before CS was the optimal sequence yielding 5.19 QALYs and incremental QALYs of 0.7, 0.20, and 0.20 versus the second-, third- and fourth-line strategy, respectively. The ranking of VDZ in treatment sequences was preserved when PRO2/3 or surgery were used as ranking criteria. In 1,780/2,000 PSA iterations (89%), VDZ before CS or as first biologic yielded the highest QALYs vs. other sequence positions.

Conclusion
The results of this simulation model using real-world evidence clearly indicate that positioning VDZ earlier in the treatment sequence may yield better patient outcomes in terms of QALYs, PROs and rates of surgery.
P536 Effectiveness, safety and persistence of treatment with ustekinumab in a cohort of patients with moderate-to-severe refractory Crohn’s Disease
Authors: Morales Bermúdez A I , Bravo Aranda A M , Martinez Burgos M , Olmedo Martín R 
Published: May 2021

Abstract

Background
Ustekinumab has proved its efficacy and safety in moderate-to-severe Crohn′s disease (CD). However, the real practice setting differs from clinical trials. Our aim was to evaluate the effectiveness and safety of ustekinumab in a cohort of real-life practice patients with CD mostly refractory to anti-TNF α agents.

Methods
Observational retrospective single-center study. All patients undergoing treatment with ustekinumab at the Digestive Diseases Department of the Regional University Hospital of Málaga and at least 16 weeks of follow-up after induction were included. The primary outcome was steroid-free clinical remission (Harvey-Bradshaw Index ≤4) at 24 and 52 weeks. Secondary objectives were combined biological remission (fecal calprotectin levels &lt;250 mcg/g and C-reactive protein &lt;10 mg/dl), safety and persistence of ustekinumab during the follow-up period.

Results
A total of 89 patients with CD treated with ustekinumab (59,6% women; median disease duration 10 years) were included. The median follow-up was 60 weeks and 55 patients reached one year of follow-up. A 39,3% of the patients had history of previous abdominal surgery and 27% had been treated with 2 or more biologics. A 25,8% and 12,4% of the patients were on steroids and immunosupresants at the induction. The percentages of steroid-free clinical remission at 24 and 52 weeks were 42% and 54% respectively (Figure 1). Combined biological remission at 24 and 52 weeks was achieved in 33% and 45% of the patients respectively. Ustekinumab persistence was 88% at 12 months of follow-up (Figure 2). There were 14 suspensions mainly due to lack of response. Only 13 adverse events were documented in 9 patients (11.5%), none of them serious.

Figure 1. Steroid-free clinical and biological remission percentages of ustekinumab at 16,24,52,76 and 104 weeks.

Figure 2. Kaplan-Meier curve showing the durability of ustekinumab throughout the follow-up period.

Conclusion
Ustekinumab was effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs in this real-life practice cohort.
P540 Real-world evidence on treatment switching in patients with moderate-to-severe ulcerative colitis: a systematic review of literature
Authors: Singh H , Wilson L , Pandey A , Tencer T , Kumar J 
Published: May 2021

Abstract

Background
Current approved therapies for the treatment of moderate-to-severe ulcerative colitis (UC) have well-established efficacy; however, some patients may fail to respond or may lose their response over time, resulting in dose escalation or treatment switching. The objective of this systematic literature review was to summarize the real-world evidence on treatment switching in UC and the associated clinical, safety and economic outcomes.

Methods
A literature search of Embase and MEDLINE (from database inception to August 2020) and conference proceedings (2017 to 2020) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The population of interest included adult patients (≥18 years) with UC who experienced treatment switching on anti-tumour necrosis factor alpha agents (anti- TNFα) - (adalimumab [ADA], infliximab [IFX], golimumab [GOL]), vedolizumab (VDZ), tofacitinib (TOFA), and ustekinumab (USTE). Outcomes of interest included all available clinical, safety and economic outcomes.

Results
Of a total 1593 studies screened, 29 met the eligibility criteria. Of these, 22 (76%) reported switching rates of 4–63% (sample size: 4-1274). A total of 7 studies reported outcomes in populations comprised entirely of switched patients (sample size: 5–76). Figure 1 includes the directed connectivity graph showing the number of studies reporting different switches. IFX to ADA was the most frequently reported switch (n=11 studies;35%). Figure 2 and Table 1 include the number of studies and proportion of patients reporting outcomes following a treatment switch, respectively. Heterogeneity was observed in patient populations, follow-up, and definitions of response/remission. In the short term (4–12 weeks), remission rates of 10–38% have been reported that increased to 49–100% in the long-term (24–57 weeks). In contrast, the clinical response rates decreased over time (30–58% over 4–12 weeks versus 15–56% over 24–57 weeks). Colectomy and corticosteroid-free remission were reported in 0–35% and 18–79% of patients, respectively. Rate of adverse events varied from 13–38%, with a switch to IFX from other anti-TNFs associated with the highest rate. One study reported higher mean quarterly total healthcare costs in patients who switched within anti-TNFs (IFX&gt;ADA, ADA&gt;IFX) compared to those who did not ($15,004 vs $9632).

Conclusion
Treatment switching in the management of moderate-to-severe UC is common in routine clinical practice and is associated with suboptimal outcomes and potentially increased costs. There remains a need for additional treatment options that provide long-term durable disease control.
P542 Clinical presentation, disease behavior and management of inflammatory bowel disease at extremes of age
Authors: Bhangale N , Desai D C , Abraham P , Gupta T , Dhoble P 
Published: May 2021

Abstract

Background
The natural history of patients with Montreal classification A2 group is well studied. Available studies on disease characteristics at extreme ages, which form 10%-25% of patients with IBD, focused on pediatric or elderly population, but not all age groups together.1
We aimed to compare the disease characteristics of pediatric- (≤16 years, P) and elderly- (≥60 years, E) onset IBD with 17-59Y middle aged group (M).

Methods
266 consecutive patients with IBD were divided into 3 groups according to age of onset. Information about disease location, extent, behavior and need for immunosuppressants / biologics and surgery was entered in pro-forma.

Results
The table shows details of 258 (P 46, M 170, E 42) patients. 8 IBD-unclassified patients were not included in the analysis as numbers were too small to compare the differences.
Among UC patients, pancolitis was more common in the pediatric population (p=0.018) and indolent behavior was more common in elderly population (p=0.005). Almost all UC patients requiring colectomy had extensive colitis(p=0.008). While among CD patients, elderly had more of ileal (p=0.04) and pediatric group had more colonic involvement (p=0.02). Perianal disease was least common in elderly CD group (p=0.03). There were no treatment differences in UC patient subgroups while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery(p&lt;0.05) and younger CD patients needed biologics much more frequently (p=0.005).

Conclusion
Pediatric UC had more pancolitis(E3) while elderly UC had milder disease with EIM less frequently. Significant co-relation was noted between colectomy and extensive colitis. Pediatric CD patients had more colonic (L2) disease with more requirement of biologics, while elderly CD group had more common ileal (L1) disease, least common perianal disease and less requirement of all treatment modalities when compared to adults. This study highlights possible different Indian IBD disease spectrum in contrast to Western literature.
1. Nimmons D, Limdi JK. Elderly patients and inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016;7:51–65.