bluuebunny/crossref_metadata_2025_split huggingface dataset:
P371 Using digital monitoring during the COVID pandemic to streamline outpatient appointments
Authors: Walsh A J , Matini L , Wilson J , Lyden S , Al-Hillawi L , Kantschuster R , Kormilitzin A , Smith T , Slater J , Payton S , White L , Woodley H , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L 
Published: May 2021

Abstract

Background
Demand for outpatient appointments (OPAs) for IBD often exceeds capacity, partly due to scheduled follow up of patients who are well. The TrueColours-IBD (TC-IBD) platform and Escalation of Therapy or Intervention (ETI) calculator was trialed as a tool to triage appointments during the pandemic

Methods
TC-IBD is a web-based programme of email prompts linked to validated disease-specific indices. The ETI calculator was created after logistic regression showed that patient-reported symptoms and quality of life could calculate the probability of therapy escalation or intervention during an OPA (Fig 1). A score ≤20 equates to ≤10% chance of escalation

The ETI calculator was developed for UC, but it was also applied to CD during the pandemic, replacing the SCCAI score with HBI. From Mar-Oct 2020 the ETI calculator was used to extend 145 OPAs (87 UC, 58 CD) from 1034 ETI assessments. TC-IBD data was assessed 2-6 weeks before a scheduled OPA. Patients were eligible for OPA extension if &gt;2 symptom (SCCAI/HBI) and 1 QoL responses (IBD Control) within 4 weeks and ETI score ≤20. Patients with extended OPAs were monitored for 3 & 6-monthly ICHOM outcomes (www.ichom.org), collected through the TC-IBD platform

Results
ICHOM outcomes available for 113/145 patients at 3 mo and 125/145 patients at 6 mo. There were no emergency department visits, no hospitalisations, no surgery, colon cancer or death at either time point in patients whose appointment was extended. 1 patient with UC required prednisolone (Table 1)

Conclusion
Routine digital monitoring of symptoms, quality of life and PROMs can safely streamline outpatient care in IBD
P375 A simulation study to evaluate the performance of a multiple imputation method to address missing data in an analysis of clinical effectiveness using the ImproveCareNow Registry of pediatric patients with Crohn’s disease
Authors: Zhang N , Liu C , King E , Chen S , Olano K , Steiner S , Colletti R , Saeed S , Strauss R , Volger S , Lo K H , Wang Y 
Published: May 2021

Abstract

Background
Patient registries are a source of real-world data (RWD) that are increasingly used to generate real-world evidence (RWE) for the safety and effectiveness of medical therapies. However, in registries, outcome data typically collected in clinical trials may be missing in some patients, creating a major challenge in evaluating RWD reliably. Clinical remission in pediatric Crohn’s disease (PCD), defined by the Short Pediatric Crohn’s disease Activity Index (sPCDAI) &lt;10, is routinely collected in the ImproveCareNow (ICN) Registry, the world’s largest registry of pediatric patients with inflammatory bowel disease (IBD). A feasibility analysis of ICN as a RWD source to estimate the efficacy of therapies in PCD found about one-third of patients were missing at least 1 of the 6 components needed to calculate the sPCDAI scores at Week 52. We conducted a simulation study to evaluate the performance of the multiple imputation (MI) method in addressing the missing data issue.

Methods
A Starting Dataset from the ICN registry included CD patients age 2 to &lt;18 yr when beginning treatment with a biologic agent other than ustekinumab during 2014 to 2019, who had a baseline visit and a “Week 52” visit. A Complete Dataset included only patients in the Starting Dataset who had all components required to calculate a sPCDAI score at the Week 52 visit. The true remission rate was calculated for the Complete Dataset. For the simulation, missing data patterns for individual sPCDAI components that were observed in the Starting Dataset were randomly imposed in the Complete Dataset. Variables that were predictive of sPCDAI scores, its components, and sPCDAI missingness were included. Ten thousand datasets were simulated for each of three scenarios: base case of the observed missingness in the Starting Dataset, 1.5 times the base case and 2 times the base case. The MI method was applied to the simulated datasets to estimate the remission rate. MI performance was measured by bias and coverage of the true remission rate from the Complete Dataset.

Results
The Starting and Complete Datasets included 1,458 and 1,212 patients, respectively. The true clinical remission rate in the Complete Dataset was 75.1% (95% CI: 72.6%-77.5%). Analysis without MI for the missing sPCDAI data resulted in underestimation of clinical remission rate, with bias about -2% to -5% (Table 1). The MI method eliminated the bias and had 100% coverage in all simulation scenarios by using a large number of independent predictors.

Conclusion
The MI method improved the validity, reliability, and efficiency of using RWD for estimating clinical remission in pediatric patients with CD and could be valuable in other registry studies.
P387 Depression in biologic-treated patients with inflammatory bowel disease during the COVID19 pandemic
Authors: Lin S , Bewshea C , Chanchlani N , Chee D , Pollok R C , Kennedy N A , Ahmad T , Goodhand J R 
Published: May 2021

Abstract

Background
Given the existential threat from COVID-19 and the consequent restrictive public health measures it is perhaps unsurprising that SARS-CoV-2 infection has been linked to increases in rates of depression in the general population. Few studies, however have addressed anxiety and depression in patients with inflammatory bowel disease (IBD) during the COVID19 pandemic. We aimed to define, in patients with IBD treated with infliximab or vedolizumab and/or an immunomodulator, the prevalence, demographic and disease-related factors associated with depression and the effect of restrictive public health measures on rates of depression.

Methods
CLARITY IBD is a United Kingdom (UK) wide, multicentre, prospective observational cohort study investigating the impact of infliximab and vedolizumab and/or concomitant immunomodulators (thiopurines or methotrexate) on SARS-CoV-2 acquisition, illness, and immunity in patients with IBD. Patients were recruited between 22nd September and 23rd December 2020 and then assessed every 8 weeks. We measured depression using the 8-item Patient Health Questionnaire (PHQ-8). Secondary outcomes were anxiety and IBD-related quality of life assessed using the General Anxiety Disorder Assessment (GAD-7) and IBD-Control questionnaires, respectively. Multivariable logistic regression models were used to identify factors independently associated with depression at entry to the study. Baseline and paired responses during the third UK government’s stay-at-home lockdown order which commenced on the 4th January 2021 were compared using the Wilcoxon signed-rank test.

Results
The prevalence of depression at entry to the CLARITY study was 26% (1794/6933): 14% patients satisfied criteria for mild, 6% moderate and 5% severe depression. Depression scores were associated with anxiety (Spearman’s rho= 0.78, p&lt;0.0001) and poorer IBD-Control-8 quality of life scores (Spearman’s rho=-0.67, p&lt;0.0001). Multivariable analysis showed that vedolizumab (vs infliximab), steroid use, female sex, younger age, remaining at home, ulcerative colitis, comorbidity and higher income deprivation were associated with depression at entry to the study (Figure 1). Paired depression scores were unchanged between study entry and when assessed during the lockdown period (p=0.91).

Conclusion
Depression was negatively associated with infliximab therapy and was unchanged during the third UK stay-at-home lockdown. Longitudinal follow up in this cohort will allow us to determine whether COVID-19 vaccination influences depression and whether depression is linked to vaccine hesitancy or impaired serological responses to SARS-CoV-2 vaccination.
P412 Effectiveness of ustekinumab in fistulising perianal Crohn′s disease refractory or intolerant to anti-TNF
Authors: Carpio D , Calviño-Suarez C , Martínez-Cadilla J , Molina G , Vázquez-Rey M T , Martí E , Fernández-Salgado E , Barreiro-de Acosta M , Hernández V , Echarri A , Diz-Lois M T , Baz A 
Published: May 2021

Abstract

Background
The management of fistulising perianal Crohn′s disease (pCD) is a challenging problem for patients and physicians. New therapeutic alternatives are needed, particularly in anti-TNF refractory patients. Data regarding ustekinumab (UST) effectiveness in pCD are scarce. Our aim was to evaluate the clinical and radiologic effectiveness of UST in pCD patients refractory or intolerant to anti-TNF.

Methods
We conducted a multi-center retrospective observational study. All patients with anti-TNF refractory pCD treated with UST were evaluated. Demographic and clinical variables including concomitant drugs were registered. Clinical response was evaluated at 16 weeks and 12 months and was defined as a reduction of 50% of draining fistulas or a marked reduction in fistula drainage. In patients with a magnetic resonance imaging (MRI) before and after treatment initiation, radiologic response was defined according to Ng Score (healed, partial response, unchanged, deterioration).

Results
Thirty-two patients were included, 68.8% female, median age 44,11 (IQR 36.28-48.56). Median time from diagnosis to UST initiation was 12.94 years (IQR 7.52-19.52), 90.6% had received previously 2 anti-TNF (37.5% also vedolizumab) and 46.9% had more than 2 fistulas. In 22 patients (68.8%) pCD was the main indication for UST treatment while in the remaining 31.2% the main indication was luminal disease. Fifteen patients (46.9%) received antibiotics at the initiation of UST, 8 (25%) combo therapy with thiopurines and 21 (65.6%) had setons. Patients received a 6mg/kg IV dose and 87.5% received 90mg/8 week SQ for maintenance. Dose intensification was needed in 20 patients (62.5%) at a median of 13 months (IQR 8.00-19.5). Fifteen patients (46,9%) achieved clinical response at week 16, while 18/30 (60%) had clinical response at 12 months (three of them were in clinical remission). Nineteen patients (59,4%) had an MRI performed pre and post-treatment at a median of 15 months (IQR 10-19). 10/19 patients (52.6%) achieved a radiological response although no patient had all fistulas healed. In the multivariate analysis the only factor associated with clinical response at 12 months was the presence of setons at UST initiation (OR 7.0; IC95% 1.3-37.9). There were no factors significantly associated with radiological response or clinical response at week 16. Four patients experienced adverse effects (three perianal abscesses and one transient skin rash).

Conclusion
Ustekinumab was effective in achieving clinical and radiological response in anti-TNF-refractory fistulising pCD patients, although clinical and radiological remission was rare. Most patients needed UST dose intensification in this highly refractory cohort. Adverse effects were infrequent, mainly perianal abscesses.
P414 Obesity is associated with a higher risk of immunogenicity to adalimumab, but not to infliximab in patients with Inflammatory Bowel Disease
Authors: Mahmoud R , Schultheiss J , Louwers J , van der Kaaij M , van Hellemondt B , Mahmmod N , van Boeckel P , Jharap B , Fidder H , Oldenburg B 
Published: May 2021

Abstract

Background
Globally, the prevalences of both inflammatory bowel diseases (IBD) and obesity have increased over the past decades. Recently, obesity has been linked to treatment failure in anti-TNF-treated patients with inflammatory bowel disease (IBD). We assessed whether obesity was associated with an increased risk of treatment failure and immunogenicity (i.e. anti-drug antibodies) among IBD patients treated with adalimumab (ADA) or infliximab (IFX).

Methods
This was a multicenter, retrospective cohort study of adult patients with IBD, treated with ADA or IFX for at least four months between 2011-2019 at a general hospital or a tertiary referral center. Obesity was defined as body mass index (BMI) &gt;30kg/m2. Adjusted hazard rates (aHR) were calculated by mixed-effects Cox regression analysis, accounting for multiple treatment episodes in individual patients and adjusted for sex, prior anti-TNF exposure, immunomodulator use, IBD phenotype (ulcerative colitis versus Crohn’s disease), age, disease duration, smoking and rheumatological comorbidity. Multiple imputation was used to replace missing values (5% for BMI).

Results
We included 728 patients, providing 2339 patient-years of follow-up and 868 treatment episodes with anti-TNF; 130 (17.9%) patients were obese. Obesity was associated with female sex (67% vs 54%), smoking (36% vs 22%), older age (median 42 vs 36 years) and prior exposure to methotrexate (25% vs 15%). In patients receiving ADA, obesity was significantly and independently associated with a higher risk of immunogenicity (Figure 1a, aHR: 2.15, 95%CI: 1.10 – 4.19) and treatment failure (Figure 2a), although significance of the latter association was lost after correcting for relevant confounders (aHR: 1.33, 95%CI: 0.87 – 2.03). In patients treated with IFX, obesity was not associated with immunogenicity (Figure 1b, aHR: 1.05, 95%CI: 0.54 – 2.03) or treatment failure (Figure 2b, aHR: 0.98, 95%CI: 0.70 – 1.39). Trough levels were significantly lower in obese patients treated with ADA, but not IFX.

Conclusion
In patients treated with ADA, but not IFX, obesity is associated with immunogenicity and possibly a higher risk of treatment failure. Proactive therapeutic drug monitoring may be warranted in obese patients treated with ADA.
P415 Paradoxical onset of Takayasu’s arteritis in patients with inflammatory bowel disease treated with anti-tumour necrosis factor-α agents
Authors: Matsune Y , Kouyama J , Tsuru Y , Shimizu K , Asami S , Matsuyama S , Katsuki S , Ishihara H , Onizawa R , Shonai S , Tatsuno M , Nishikawa Y , Takeuchi K , Watanabe M , Nakamori Y , Hirayama A , Toyoda J , Ikeda A , Madarame A , Nishio M , Ogashiwa T , Matsubayashi M , Fujii A , Kimura H , Kunisaki R 
Published: May 2021

Abstract

Background
Takayasu’s arteritis (TA) is a rare complication associated with inflammatory bowel disease (IBD). TA is a granulomatous systemic vasculitis of uncertain aetiology affecting large arteries, predominantly the aorta and its main branches, leading to stenotic and expansible lesions. The estimated prevalence of coexisting of TA in patients with ulcerative colitis (UC) is 0.3%, and that in patients with Crohn’s disease (CD) is 0.1%. Anti-tumour necrosis factor-α (TNF-α) agents are used to treat both TA and IBD, although some patients with IBD paradoxically develop TA during treatment with anti-TNF-α agents. However, data regarding the incidence and clinical features of TA in such cases are lacking. This study was performed to clarify the prevalence, risk factors, and clinical features of TA that develops paradoxically during treatment with anti-TNF-α agents in patients with IBD.

Methods
Consecutive patients with IBD who were regularly seen at our centre, a tertiary IBD centre in Japan, from 2000 to 2019 were included in this retrospective single-centre study. We evaluated the prevalence of TA according to the presence or absence of treatment with anti-TNF-α agents and the patients’ clinical manifestations.

Results
Of 1846 patients with UC and 1249 patients with CD, 7 (0.23%) patients with UC developed TA. The prevalence of TA in patients treated with anti-TNF-α agents was significantly higher (4/254, 1.6%) than that in patients without anti-TNF-α agent treatment (3/1592, 0.19%) (p=0.0087, Fisher’s exact test). Among four patients with UC who paradoxically developed TA during treatment with anti-TNF-α agents, three (75%) received infliximab, one (25%) received adalimumab, and one (25%) received golimumab. One was male and three (75%) were female. The median interval from starting treatment with anti-TNF-α agents to diagnosis of TA was 49.0 (34–63) months. All patients had pancolitis as well as persistent active colitis resistant to anti-TNF-α antibody treatment. The treatments for TA administered after anti-TNF-α therapy were as follows: Two (50%) patients discontinued anti-TNF-α agent therapy, three (75%) were treated with prednisolone, and one (25%) received tocilizumab. No patient required an operation for TA.

Conclusion
To our knowledge, this is the first study to show the prevalence and clinical features of TA in patients with IBD following administration of anti-TNF-α agent therapy. Although TA is a rare complication, our results suggest that it can develop as paradoxical reaction following administration of anti-TNF-α agents.
P484 Remote monitoring allows an individualized approach and showed excellent usability at the infusion unit
Authors: Fierens L , Geens P , De Dycker E , Paps A , Lambrechts T , Sabino J , Vermeire S , Ferrante M 
Published: May 2021

Abstract

Background
Given the high impact on health-related quality of life (HRQoL), IBD patients may benefit from continued monitoring by specialized caregivers. Patient-reported outcomes (PRO) can be collected through telemedicine in a reliable way, allowing to monitor patients even in between hospital visits and supporting patient-physician interaction. The aim of this study was to implement an electronic questionnaire into routine clinical practice and to explore its added value.

Methods
Since May 2020, all IBD patients visiting the infusion unit of our tertiary referral centre (+/- 130 patients/week) receive an electronic questionnaire one week prior to their visit. Questions about disease activity are included through the two-component PRO (PRO2), and about HRQoL in form of the IBD Disk, which visually shows the impact of disease on ten different health domains over time (lower scores seen in quiescent disease). Based on PRO2 scores, clinical remission was defined as a liquid stool frequency ≤1 and an abdominal pain score ≤1 in patients with Crohn’s disease (CD), and as a stool frequency score ≤1 and no rectal bleeding in patients with ulcerative colitis (UC). We evaluated PROs and participation rate, and the System Usability Scale (SUS) was used to evaluate usability of the new system.

Results
In Jan-Feb 2021, a total of 447 unique IBD patients completed the full questionnaire at least once [48.0% participation rate, 62.9% CD, 53.0% male, median age (IQR) 46.5 (33.8–56.8) years, 94,9% on biologic therapy, 61.5% in clinical remission, Figure 1]. No association was found between sex, age (group) or IBD type and adherence to the questionnaire. Median (IQR) IBD Disk scores were significantly lower for remitters versus non-remitters [11 (3–25) vs. 40 (21–59), p&lt;0.001]. The most affected health dimension in all patients regardless of remission state was energy with differences for remitters [median (IQR) 2 (0–5)] and non-remitters [median (IQR) 6 (3–8)]. Whereas all ten health dimensions of the IBD Disk were highly correlated with disease activity (p&lt;0.001, Figure 2), no correlation was found with disease type, sex, age (group) or type of biologic therapy. In Feb 2021, 375 patients of the same cohort were randomly invited to complete the SUS. A median (IQR) SUS score of 85 (71.25–91.25) was found, indicating excellent usability of the new system (n=113).

Conclusion
The results show high correlation between disease activity and the impact on HRQoL, especially energy levels. Based on these PROs a more individualized approach at the infusion unit could be installed. This system is currently also implemented for IBD patients who do not visit the infusion unit but receive oral or subcutaneous therapy or no maintenance therapy.
P491 Infectious risk of vedolizumab compared with other biological agents in the treatment of Inflammatory Bowel Disease
Authors: Innocenti T , Roselli J , Lynch E N , Apolito P , Parisio L , Bagnoli S , Macrì G , Rogai F , Milani S , Galli A , Milla M , Dragoni G 
Published: May 2021

Abstract

Background
Vedolizumab (VDZ) is a gut selective anti-α 4β 7 integrin antibody for the treatment of Inflammatory Bowel Disease with a well-known optimal safety profile. We aimed to compare the risk of infections of VDZ with that of anti-TNF drugs and ustekinumab, in patients with both ulcerative colitis (UC) and Crohn’s disease (CD).

Methods
All CD and UC patients undergoing biological treatment at our centre between June 2013 and June 2020 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of exposure-adjusted infection rate of vedolizumab with that of anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs).

Results
The overall exposure-adjusted infection rate was 11.5/100 PYs. Detailed information about the infectious complications related to the different biologics is reported in Table 1. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations, and gut infections. The rate of serious infections was 1.3/100 PYs. Among the 85 patients who were on a VDZ therapy, 17 (3 CD and 14 UC, median age 64, IQR 31–68) suffered an infectious complication. The exposure-adjusted incidence rate for vedolizumab was 17.5/100 PYs, with CD patients having a lower infection risk compared with UC patients (p = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the VDZ group (p = 0.0001).

Conclusion
Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with UC have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this could be due to the gut-selective mechanism of action of vedolizumab.
P583 Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn’s disease: results from a large Italian cohort study
Authors: Mocci G , Cuomo A , Allegretta L , Aragona G , Colucci R , Della Valle N , Ferronato A , Forti G , Gaiani F , Graziani M G , Lorenzetti R , Luzza F , Penna A , Pica R , Piergallini S , Rodinò S , Scarcelli A , Zampaletta C , Cicerone C , Cocco A , De Angelis G , Donnarumma L , Pranzo G , Franceschi M , Gallina S , Grasso G , Larussa T , Luppino I , Faggiani R , Fanigliulo L , Pagnini C , Perazzo P , Sacco R , Sebkova L , Serio M E , De Monti A , Picchio M , Elisei W , Maconi G , Tursi A 
Published: May 2021

Abstract

Background
Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics

Methods
194 CD patients (108 males and 86 females, mean age 48 years (range 38–58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients

Results
At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up.
A logistic regression, UST therapy as thirdline therapy (after both anti-TNFα and vedolizumab), FC &gt;200 μg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment

Conclusion
Ustekinumab seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.