bluuebunny/crossref_metadata_2025 huggingface dataset:
P345 Food-related quality of life in adults with Inflammatory Bowel Disease is influenced by restrictive eating behaviour, disease activity and surgery: a prospective multi-centre study
Authors: Day A , Yao C K , Costello S , Andrews J , Bryant R
Published: May 2021

Background

Measuring food-related quality of life (FRQoL) quantifies the psychosocial impact of eating and drinking.1 The influences on FRQoL in people with inflammatory bowel disease (IBD) are not well explored, despite IBD being a chronic disease affecting the digestive tract. This study aimed to characterise and identify any patient or disease-related predictors of FRQoL in individuals with IBD.

Methods

Adults with a formal diagnosis of IBD were recruited to a prospective multi-centre cross-sectional study between April 2018 and December 2019. Participants completed questionnaires measuring FRQoL (IBD-FRQoL-29: minimum/poor 29, maximum/greatest 145), clinical disease activity (active disease: Harvey Bradshaw Index >4 active disease, Simple Clinical Colitis Activity Index >2, restrictive eating behaviour (Nine Item Avoidant/Restrictive Screen: minimum 0, maximum 45), mental health (DASS-21: minimum 0, maximum 126) and other patient and disease-related variables.

Results

One hundred and eight participants completed the questionnaires. The majority of the cohort had UC (69/108, 64%) and there was almost equal distribution of those with quiescent (48%) and active (52%) disease The mean FRQoL of individuals with IBD was 79 (95% CI 75, 84) (see Figure 1). Poorer FRQoL was seen in those with restrictive eating behaviour associated with fear of a negative consequence from eating (p<0.0001) and reduced appetite (p<0.030). Greater FRQoL was seen in those with lower disease activity (p<0.0001) and previous IBD surgery (p=0.240). FRQoL was not influenced either way by IBD phenotype, duration, or gender. The majority of participants obtained their dietary information from the internet (60%) or gastroenterologist (46%).

Conclusion

FRQoL in people with IBD is poorer in those with restrictive eating behaviours and clinically active disease. Interestingly, it was greater in those with previous IBD surgery. Further research is required to validate these associations and explore longitudinal effects of poor FRQoL on patient outcomes and potential strategies for prevention or management of impaired FRQoL in IBD.

Reference
P356 A comparison of innovative strategies to promote engagement with an IBD patient portal
Authors: Carlson S , McCartney S , Harrow P
Published: May 2021

Background

Patient portals are available on most major electronic health record (EHR) platforms and present many opportunities to improve patient engagement with services, the quality of data captured and therefore healthcare outcomes and patient satisfaction.

Our centre looks after 5100 patients with IBD. We recently adopted the EPIC Systems patient portal MyChart which allows patients to view results, letters and complete patient reported outcomes (PRO). At baseline, few patients were registered for this platform. Our aim was to compare patient engagement with MyChart using a low and higher cost approach and to evaluate patient satisfaction with the platform.

Methods

160 consecutive patients were invited to join MyChart between September and October 2020.

The low-intensity intervention group were invited to join MyChart via a standardised email without further communication. Newly registered patients and active patients were sent a portal message with disease-specific PRO questionnaire 7 days prior to clinic (HBI, SCCAI and IBD Control). Patients in the high-intensity intervention group received a telephone reminder to encourage completion at each step, which took on average 2 minutes, in addition to email. Engagement with the platform was measured prospectively. After clinic a patient-experience questionnaire was sent to all patients who signed up to the platform.

Results

72 patients were included in the low intensity group and 88 in the high intensity group. At baseline only 33% patients were already signed up to MyChart. Significantly more patients newly registered with the patient portal following the high intensity intervention compared to the low (75% vs. 30%, p <0.0001). Overall, patients in the high intensity group were significantly more likely to complete the PRO compared to the low (53% vs. 28%, p=0.002). Patients already registered were 5 times more likely to complete the PRO in the high intensity group compared to low (p=0.017). Platform engagement was not significantly impacted by gender or ethnicity. There was a trend toward lower engagement in patients over 65.

63 patients provided feedback. 87% found MyChart easy to use and 94% said they would complete the PRO questionnaires again.

Conclusion

In our patient cohort, a higher intensity strategy significantly increased patient registration and engagement with a new patient portal at a minimal cost of time and resource. Healthcare providers can facilitate patient engagement with patient portals and overcome barriers to adoption to unlock transformative opportunities for better quality IBD care, disease monitoring and population-based research.
P365 Correlation between patient-reported outcomes (PROs) and patient-reported disease activity in Ulcerative Colitis (UC): Findings from the ICONIC study
Authors: Ghosh S , Casellas F , Kligys PhD K , Sanchez Gonzalez Y , Peyrin-Biroulet L
Published: May 2021

Background

This analysis aimed to examine the correlation of patient-reported outcomes (PROs) with patient-reported disease activity, and to identify individual questions of the Patient Simple Clinical Colitis Activity Index (P-SCCAI) associated with Work Productivity and Activity Impairment (WPAI) questionnaire domains in patients from the ICONIC study.1

Methods

ICONIC enrolled unselected outpatients (N=1804) with recent-onset UC.1 Correlations between PRO measures (Rating Form of Inflammatory Bowel Disease Patient Concerns [RFIPC], Patient Health Questionnaire-9 [PHQ-9], and Short Inflammatory Bowel Disease Questionnaire [SIBDQ]) at baseline (visit [V]1) and 2 years (V5) were assessed using Spearman’s rank correlation coefficient. WPAI domains and PHQ-9 were evaluated at V1 and V5 using a multivariable logistic regression model with individual P-SCCAI questions.

Results

Significantly higher work productivity impairment scores, lower reported quality of life (QoL), and higher worries/concerns at V1 and V5 were observed in patients with active disease (P-SCCAI ≥5) vs inactive disease (P-SCCAI <5) (Figures 1 and 2). A strong correlation (0.70–0.89) was found between the SIBDQ and the P-SCCAI and PHQ-9 (Table 1). WPAI presenteeism, total activity impairment and total work productivity impairment were moderately correlated (0.40–0.69) with P-SCCAI and PHQ-9 (Table 1). At V1, a significant positive association of disease severity and nocturnal bowel urgency was observed with WPAI presenteeism, absenteeism, and total activity impairment. At V1 and V5, lower patient-assessed PHQ-9 scores were significantly associated with female gender, no bowel urgency, and no joint pain.

Conclusion

These observational data in patients with UC suggest strong correlations between some PRO measures and patient-reported disease activity. Nocturnal bowel urgency was a key driver of total work productivity impairment, suggesting it is an important PRO to monitor when assessing overall patient QoL.

Reference
P368 Proactive Therapeutic Drug Monitoring is more effective than Conventional Management in Inducing Fecal Calprotectin remission in Inflammatory Bowel Disease
Authors: Pedro J , Rodrigues I , Fernandes S , Gonçalves A R , Bernardo S , Baldaia C , Valente A , Moura Santos P , Correia L , Tato Marinho R
Published: May 2021

Background

Proactive therapeutic drug monitoring (pTDM) may potentially improve disease control and treatment outcomes in inflammatory bowel disease.

Methods

Using a prospectively maintained database we compared 135 patients following a pTDM protocol aiming at an Infliximab trough level (IFXTL) between 5-10 µg/mL with sequential measurements of Fc, with 108 patients from a retrospective group under conventional management (noTDM). We evaluated the rates of Fc remission (<250 µg/g), and other clinical outcomes at 2-years of follow up.

Results

pTDM associated with higher rates of Fc remission (69.6% vs 50.0%; P=0.002), and steroid-free clinical remission (78.4% vs 55.2%, P=0.028) with a trend for clinical remission (79.3% vs 68.5%, P=0.075). There was no difference in treatment discontinuation (P=0.195), hospitalization (P=0.156), and surgery (P=0.110). Higher IFXTL associated with Fc remission at week 14 (6.59 vs 2.96 µg/mL, P<0.001), and at the end follow-up (8.10 vs 5.03 μg/mL, P=0.001). Fc remission associated with higher rates of clinical remission (85.8% vs 56.8% P<0.001), steroid-free clinical remission (86.9% vs 50.0% P<0.001), and lower rates of IFX discontinuation (8.8% vs 36.8%, P<0.001), and hospitalization (13.5% vs 33.7%, P<0.001) with a non-significant trend for surgery (6.1% vs 12.6%, P=0.101).

Conclusion

PTDM was more effective than conventional management in inducing Fc remission which associated with improved clinical outcomes.
P379 Variations in disease monitoring between Inflammatory Bowel Disease patients on intravenous and subcutaneous biologic agents
Authors: Hilley P , Li Wai Suen C , Srinivasan A , Choy M C , De Cruz P
Published: May 2021

Background

The availability of subcutaneous (SC) administration devices of biologics in addition to intravenous (IV) administration has influenced patients’ and clinicians’ preferences towards initiating or transitioning to SC administration particularly during the COVID-19 pandemic. Whilst SC administration improves patient convenience and reduces demands on infusion centres we hypothesised that the reduction in healthcare contact associated with SC therapies may reduce the opportunities available for objective disease assessment. We aimed to compare the uptake of objective assessment of disease activity between patients receiving IV and SC biologic therapy.

Methods

Patients on maintenance infusion-based or subcutaneous biologic therapy for IBD between 09/2020 and 02/2021 were identified from a prospectively maintained database at an Australian tertiary IBD centre. Patients scheduled for review in IBD clinic for a prescription of maintenance biologic therapy during the follow-up period were included. Clinic records were reviewed to determine whether patients had undergone objective disease assessment including: biochemical investigation (C-Reactive protein) and Faecal Calprotectin (FCP) within the preceding 8 weeks and/or endoscopic/imaging assessment within the preceding 6 months of clinic review. Frequency of objective disease assessment was compared between patients who received IV versus SC maintenance biologic therapy.

Results

A total of 307 patients were included: IV maintenance n=195 (Infliximab n=135; Vedolizumab n= 60) and SC maintenance n=112 (Adalimumab n=54; Ustekinumab n=54; Golimumab n=4). Patients who received IV biologics were more likely than the SC cohort to have had biochemical assessment in the form of CRP (90% vs 72%, p<0.001) and FCP (54% vs 46%, p=0.16). Patients in the SC biologic cohort were more likely not to have had investigations completed prior to their clinical review (20% versus 4%, p<0.001). There was no difference in the overall rates of complete objective disease assessment (CRP/FCP and endoscopy/imaging) between the IV and SC cohort (28% vs 30% (p=0.74).

Conclusion

Patients on subcutaneous biologic therapies in our cohort were less likely to have had objective disease monitoring than those receiving intravenous biologics prior to scheduled IBD clinic review. Route of of biologic administration may influence rates of uptake of objective disease activity assessment. Tools that safeguard against the disparity of monitoring uptake, including messaging prompts and patient-centric mobile applications may help standardise the approach to objective disease assessment independent of the route of biologic administration.
P400 Bowel ultrasonography, a non invasive easy-to-use method to predict the need to step-up therapy in inflammatory bowel disease patients
Authors: Les A , Iacob R , Cotruta B , Saizu R , Gheorghe L , Gheorghe C
Published: May 2021

Background

Inflammatory bowel diseases (IBD) are chronic conditions that require multiple endoscopic and imaging assessments. Recent guidelines recommend bowel ultrasonography (BUS) as a complimentary imaging technique to assess transmural and extraintestinal lesions. The aim of the present study was to evaluate the accuracy of BUS in predicting the need to step-up therapy in IBD patients.

Methods

117 IBD patients were included in the study (28 diagnosed with ulcerative colitis, 89 with Crohn’s disease). Following bowel ultrasound features bowel ultrasound features have been investigated: bowel wall thickness, loss of wall stratification, presence of bowel wall Doppler signal, the presence of hyperechoic spots inside the bowel wall, the irregularity of the external layer of the wall, the presence of creeping fat (mesenteric hypertrophy), the presence of visible lymph nodes. Patients were followed up for the next 6 months and data regarding their therapy was noted.

Results

During follow-up, therapeutic step-up, or biological treatment intensification (study outcome) were considered in 49.5% of cases in our study group. In a univariate analysis all the studied bowel ultrasound features but not the disease phenotype were significantly associated with the outcome. In the multivariate analysis only mean bowel wall thickness (<0.0001) and the presence of bowel wall Doppler signal (0.007) were independent predictors. Using the logistic regression prediction model, a score to evaluate the need of IBD treatment intensification could be calculated - Bowel Ultrasound Score (BU Score). The AUROC of the new BU score as a predictor for treatment intensification at 6 months in patients with IBD is 0.92, with a sensitivity of 84% and a specificity of 89%, indicating a good clinical utility. For the same outcome, AUROC for CRP was 0.81 whereas for fecal calprotectin was 0.85.

Conclusion

As the “treat to target concept” is the currently accepted novel treatment paradigm, incorporating BUS in IBD patients monitoring (BU score) provides an easy-to-use and readily available tool to stratify patients in need for therapeutic intensification.
P407 Thiopurines: use them or lose them? Results of an international survey
Authors: Sousa P C , Ministro P , Armuzzi A , Dignass A , Høivik M L , Magro F
Published: May 2021

Background

With the development of new drugs for inflammatory bowel disease (IBD), the role of thiopurines in the therapeutic algorithm of Crohn’s disease (CD) and Ulcerative Colitis (UC) is questioned. We aimed to investigate the current practice and future perspective of IBD physicians regarding the efficacy, safety, and role of precision medicine of thiopurines in IBD.

Methods

A 29-question web-based survey was developed and distributed to IBD physicians internationally, via national IBD associations and word of mouth. The final survey form was reviewed and approved by the clinical committee of ECCO. In the absence of a universal definition of an “IBD expert”, we defined them as senior physicians observing more than 20 patients per week.

Results

Complete answers from 408 physicians from 50 countries were obtained, the majority from European countries. Participants were mainly experienced physicians in IBD, with 26.0% meeting our definition of “IBD expert”. Only four physicians reported not using thiopurines in clinical practice. Azathioprine was the most used drug (97.1% of participants), while 61.3% of physicians reported using mercaptopurine; only 6.6% of participants used thioguanine. Most respondents used thiopurines in both monotherapy and in combination therapy, for both CD and UC, and consider them as effective treatments (Figures 1 and 2). Respondents tended to consider thiopurines as drugs with a good safety profile, with the agreement of 61.5% of the overall cohort; this was true especially in patients aged between 30 and 50 years old, with the agreement of 80.2% of the overall cohort (Figure 3). Access to TPMT activity assessment and metabolites measurement varied regionally. Physicians considered access to metabolites measurement as an important tool to improve thiopurines’ efficacy and safety, and to increase confidence when prescribing these drugs (Figure 4). Only a minority of the physicians (~6%) considered that thiopurines will not be used in the future in IBD, while 57.8% believed they will still be used both in mono and combination therapy in CD and UC.

Conclusion

Despite the many emerging treatments in IBD, thiopurines will still be part of the treatment algorithm of both CD and UC in the future. Access to tools for precision medicine varies around the globe, and wider implementation of these instruments, especially metabolite measurement, may improve confidence in thiopurines prescription, improving safety and efficacy.
P421 Treatment optimization with vedolizumab in treatment-refractory patients with ulcerative colitis and Crohn’s disease – a real-world two-center cohort study
Authors: Attauabi M , Vind I , Pedersen G , Bendtsen F , Benedict Seidelin J , Burisch J
Published: May 2021

Background

Real-world data about treatment optimization of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD) are scarce. Therefore, we aimed to investigate the influence of administration of a supplementary dose of vedolizumab at week ten on short and long-term outcomes.

Methods

A retrospective two-center cohort study was conducted between November 2014 and November 2019. The primary outcomes were clinical remission (CR) at weeks 14, 30, 52, and 104 and Sustained CR (SCR) defined as CR at week 14 through week 52.

Results

The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. As shown in Table 1, patients with CD receiving or not receiving the additional dosing at week ten were comparable in terms of disease activity at weeks 0 and 6, while patients with UC receiving the dosing at week 10 experienced higher disease activity at week 0 but not week 6. The overall efficacy of vedolizumab in UC and CD stratified according to treatment with the optional dosing at week ten is summarized in Figures 1 and 2, demonstrating no statistically significant difference among patients receiving or not receiving vedolizumab at week 10. Furthermore, the optional dosing of vedolizumab at week 10 (odds ratio (OR)=0.23 (95%CI 0.03-1.17), and OR=0.68 (95%CI 0.22-2.04)), was not associated with CR at week 52 among patients with UC and CD, respectively.

Conclusion

Vedolizumab is effective in achieving short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10 did not improve long-term outcomes.
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

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

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 >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI<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

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 >4.5% or decreased cost of rivaroxaban ≤$280 can reduce the ICER to <$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 <$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

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

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

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

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 <250 mcg/g and C-reactive protein <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

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>ADA, ADA>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

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<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.
P544 Point-of-care finger prick test for C-reactive protein, infliximab and adalimumab serum concentrations
Authors: Volkers A , Löwenberg M , Bray K , Bahur B , Braad M , Abeling Y , Gecse K , Duijvestein M , Ponsioen C , D’Haens G
Published: May 2021

Background

Point-of-Care tests (POCTs) allow instant measurement of inflammatory markers and/or drug concentrations. However, currently available POCTs for infliximab (IFX) and adalimumab (ADL) serum concentrations are time consuming. Recently, a new POCT device (ProciseDx, San Diego, CA, USA) was developed which conveniently measures C-reactive protein (CRP), IFX and ADL capillary concentrations within minutes. We aimed to validate this device by comparing POCT results with conventional laboratory tests for serum CRP, IFX and ADL in patients with inflammatory bowel disease (IBD).

Methods

IBD patients requiring routine measurement of serum CRP, IFX or ADL were invited to participate. Along with serum collection, 20μl of capillary blood was obtained via finger prick and dispensed in a cartridge with a buffer, and placed in the POCT device providing results within two to four minutes. Forty patients were needed to validate the CRP POCT, as this assay was already previously validated in a different population. For the IFX and ADL assays, 120 patients using IFX or ADL were required to validate the POCT. Agreement between the laboratory serum assay and POCT was visualized on a scatter diagram and a Bland-Altman plot. Deming regression was calculated to demonstrate agreement. In addition, Pearson’s correlation coefficient was calculated.

Results

Until now, 41 patients have been enrolled for the CRP assay, 120 patients for the IFX and 46 patients for the ADL assay. Two ADL patients were sampled twice (n=48). Significant correlations were found for CRP, IFX and ADL (r=0.98, r=0.88 and r=0.86 respectively, Fig. 1). Deming regression analysis of the CRP assay resulted in a slope of 0.71 (95% CI 0.49 to 0.93) and 1.5 (95% CI -0.44 to 3.50) for the intercept. For the IFX assay, the slope was 1.1 (95% CI 0.83 to 1.3) and the intercept was 1.4 (95% CI -0.47 to 3.4). For the ADL assay, the slope was 0.97 (95% CI 0.64 to 1.3) and the intercept was 2.3 (95% CI -0.64 to 5.2).

Conclusion

A novel POCT using a finger prick approach provides a rapid, user friendly and reliable measurement of CRP, IFX and ADL concentrations within minutes. The capillary CRP was slightly lower than the venous serum CRP, which was consistently observed and considered clinically irrelevant in this cohort.
P566 Impact of induction therapy and clinical remission on resting energy expenditure in children with Crohn’s Disease
Authors: Kornitzer G , Breton J , Poinsot P , Godin D , Grzywacz K , Deslandres C , Groleau V
Published: May 2021

Background

Crohn’s Disease (CD) is known to affect nutritional status and linear growth in affected children. Patients with CD often have decreased oral intake, malabsorption, and increased intestinal losses. Basal metabolic rate may be affected by chronic inflammation and states of anorexia or malnutrition in these patients. In this study, our aim was to compare the effect of different induction regimens in children with CD on resting energy expenditure (REE) and nutritional status.

Methods

We recruited patients under 18 years old with new-onset CD or relapse, diagnosed at our centre over a three-year period from July 2016. Patients included had one of the following induction regimens: corticosteroids, exclusive enteral nutrition (EEN), or anti-TNF therapy (Infliximab). REE was assessed at baseline and 6 to 8 weeks after induction. REE (kcal/d) was measured using an open-circuit indirect calorimeter with computerized metabolic cart (Vmax Encore, Vyaire Medical). Secondary outcomes included anthropometrics and clinical and biochemical response, defined by improved wPCDAI and negative inflammatory markers and fecal calprotectin, respectively.

Results

17 patients were enrolled and 8 patients excluded (loss to follow-up (n=3), therapeutic change (n=3), revised diagnosis (n=2)). 9 patients completed REE assessments (44.4% anti-TNF (n=4), 44.4% EEN (n=4), 11.1% corticosteroid (n=1)). 3 out of 4 patients on anti-TNF had clinical and biochemical response, while only 1 of 4 patients responded to EEN. For patients in the EEN group, mean BMI change was +0.9 (SD 0.4), compared to +0.4 (SD 1.1) in the anti-TNF group. There was no difference in REE change between treatment groups. Data was then pooled based on response to treatment. 100% of non-responders had increased per cent of predicted REE (REEPP), while 75% of responders decreased their REEPP. Mean REEPP change in non-responders was +12.5% (1, 22) vs. -4.3% (-10, 6) in responders.

Figure I. Relationship between REE and weight at baseline and on follow-up in non-responders.

Figure II. Relationship between REE and weight at baseline and on follow-up in responders.

Conclusion

Our results suggest that induction regimen did not impact REE change on follow-up. In our patients, clinical response to therapy was related to a tendency to decrease REE. Patients who did not achieve remission after induction therapy increased their REE. We suspect that this increase in basal metabolic rate is related to persistent inflammation despite improved nutritional status. Further studies with larger patient populations are needed to infer significance and compare subgroups based on body composition.