bluuebunny/crossref_metadata_2025_split huggingface dataset:
P449 Cost Effectiveness of a Proactive Therapeutic Drug Monitoring Strategy in Patients with Inflammatory Bowel Disease Receiving Infliximab
Authors: Doherty J , Varley R , Healy M , Dunne C , Mac Carthy F , Mc Kiernan S , Hartery K , Kevans D 
Published: May 2021

Abstract

Background
Proactive therapeutic drug monitoring (TDM) has not demonstrated improved therapy outcomes compared with clinically-based dosing strategies. While the use of proactive TDM incurs additional assay-related costs this strategy may be cost-effective due to TDM-driven therapy dose de-escalation and discontinuation.

Methods
We aimed to assess if proactive-TDM is cost-effective in clinical practice. A proactive TDM strategy was utilized in our unit with infliximab (IFX) and antibody-to-infliximab (ATI) levels assessed at trough in all inflammatory bowel disease(IBD) patients receiving IFX. Baseline demographics and IFX dosing schedules were documented. Patients were grouped based on disease activity status. Patients with IFX levels outside therapeutic range had dosing adjusted as appropriate. IFX dose adjustments were not protocolized and were at physicians discretion. IFX dosing regimens following proactive TDM were documented and net effect on IFX infusions number over the subsequent year extrapolated. Increase or decrease in drug-related costs on an annualized basis were estimated.

Results
108 patients were included. Median age 36 years. 46% were female. 36% had ulcerative colitis, 60% Crohn’s disease. 35% were receiving concomitant immunomodulators. 56% were in remission at the time of TDM. 44%, 30% and 26% had IFX levels &lt; 3 µg/mL, 3 – 7 µg/mL and &gt; 7 µg/mL. IFX levels were significantly lower in patients with active disease compared with those in remission(p=0.008). Following proactive TDM assessment 37%, 11%, 36%, 13%, 2% and 1% of patients had no treatment change, therapy discontinuation, interval shortening, interval lengthening, dose increase and dose decrease respectively. Cost-effectiveness analysis focused on patients in remission (n=59). The use of proactive TDM-based IFX dosing resulted in a projected annualized reduction of 19.5 and 28.5 infusions due to IFX discontinuation and interval lengthening; the projected annualized increase in infusions was 39.1 and 4.3 due to IFX interval shortening and dose increase. This resulted in a net projected reduction of 4.7 IFX infusions per annum. Utilizing publicly available list prices for originator and biosimilar IFX and accounting for assay cost, projected cost savings resulting from proactive-TDM was 9105.0 and 6840.7 Euro per annum.

Conclusion
Proactive TDM in IBD patients in remission resulted in a modest reduction in the projected annualized number of infusions in our unit with consequent minor drug-related cost savings. Proactive-TDM encouraged cost-effective prescribing of IFX, however, the effect was minor. The frequency at which proactive TDM should be performed and whether subsequent rounds of proactive-TDM would continue to deliver similar cost savings is uncertain.
P463 COVID-19 vaccination willingness and hesitancy in patients with Inflammatory Bowel Diseases (IBD): analysis of determinants in a national survey of the Italian IBD patients’ association (AMICI Onlus)
Authors: Costantino A , Noviello D , Conforti F S , Aloi M , Armuzzi A , Bossa F , Ficari F , Leone S , Manguso F , Mocci G , Orlando A , Pironi L , Radice S , Rizzello F , Tongiorgi A , Costantino C , Vecchi M , Caprioli F 
Published: May 2021

Abstract

Background
Vaccine hesitancy, the delay in acceptance or refusal of vaccination despite its availability, represents a threat to the diffusion and lethality of infectious diseases. COVID-19 vaccination has been recommended by national and international organizations in patients with Inflammatory Bowel Diseases (IBD). The aim of the study was to evaluate COVID-19 vaccine willingness and hesitancy in a population of Italian patients with IBD, and their determinants.

Methods
In February 2021 an online questionnaire focused on COVID-19 vaccine was proposed to a representative sample of Italian IBD patients. Socio-demographic characteristics, IBD features, lifestyle, perception of COVID-19, general attitude towards vaccinations and to COVID-19 vaccines were investigated. Patients were divided into willing, hesitant and refusive towards COVID-19 vaccine. The hesitation reasons were investigated. The associations between baseline characteristics and willingness (determinants) were evaluated by calculating crude and adjusted Odds Ratio (AdjOR) with 95% confidence intervals (CI).

Results
The baseline characteristics are shown below. 1252 surveys were collected. 1005 (80.3%), 222 (18.1%) and 33 (2.63 %) patients were defined as willing, hesitant and refusive, respectively. Concerns for vaccine adverse effects constituted the main reason for refusal (73.4%) (Figure). 49.1% of hesitant patients reported that presence of IBD exerted an influence on their answer. Among the patients willing to be vaccinated whenever possible, 78.2% (786) thought that their IBD represented a valid motivation to access vaccination with priority. Willingness to COVID-19 vaccine was significantly associated with adherence to previous vaccinations (AdjOR 17.6, 95% CI 11.4–27.2), male gender (1.68 95% CI 1.16–2.43), graduation degree (1.48, 95% CI 1.03–2.13), perceived higher risk of COVID-19 due to IBD (1.47, 95% CI 1.05–2.08), alcohol intake (1.69, 95% CI 1.16–2.45). Conversely, the hesitancy was significantly associated with use of complementary and alternative medicines (0.58, 95% CI 0.36–0.92). Notably, 54.5% of patients were under the impression to have a higher risk of COVID-19 and 31.8% a more severe course due to their IBD.

Conclusion
Most IBD patients would accept COVID-19 vaccines, though one out of five is hesitant to date, principally due to fear of adverse events. The knowledge of determinants and reasons for COVID-19 vaccination acceptance could be a key element in developing targeted communication strategies to address vaccine hesitancy.
P470 Ustekinumab Trough Levels are not Associated with Clinical Response in Inflammatory Bowel Disease Patients
Authors: Zelinkova Z , Lipovska A , Otottova K , Lucenicova J , Kadleckova B 
Published: May 2021

Abstract

Background
Ustekinumab (UST) has been shown to effectively induce and maintain remission in inflammatory bowel disease (IBD). Only a few studies thus far have focused on UST pharmacokinetics suggesting that both, trough levels after i.v. induction as well as trough levels during stable maintenance might be associated with clinical and endoscopic response to UST. Data from real-world cohorts in this setting are scarce. Therefore, the aim of our study was to assess whether clinical response to UST was associated with a specific pharmacokinetic pattern.

Methods
All IBD patients treated with UST in one tertiary IBD centre between January 2017 and August 2020 were retrospectively retrieved from the database. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. Clinical response was defined as a decrease of HBI of ≥2 points or partial Mayo score ≥3 points. Patients not responding to therapy by week 16, or loosing original response received dose escalation from 90mg s.c. every 8 weeks to 90mg every 4 weeks. UST through levels were assessed by commercially available ELISA kit (IDKmonitor®) at week 8 after i.v. induction and/or during maintenance therapy after a minimum period of 16 weeks of treatment.

Results
In total, 61 IBD patients were included (mean age 38 years, range 22–70; 38 women; 54 CD/6 UC/1 IBD-U). All patients were antiTNF experienced, minority (11; 18%) had also been treated with vedolizumab prior UST. Thirty-nine pts (64%) were responders, out of these 15 pts (38%) required dose escalation at some point of the treatment due to secondary loss of response.
UST through levels at week 8 were significantly higher than the maintenance levels (mean 5.6±SEM 0.7µg/mL vs. 2.2±0.3µg/mL; p&lt;0.001). There were no significant differences between responders and non-responders neither in trough levels after induction (5±0.8µg/mL vs. 6.4±1.1µg/mL, p=n.s.), nor in trough levels during maintenance therapy (2.3± 0.4µg/mL vs. 1.9 ±0.4µg/mL, p=n.s.). Patients requiring dose escalation did not differ from stable responders in maintenance trough levels (2.4±0,6 µg/mL vs. 2,3 ±0,4 µg/mL).

Conclusion
In this limited size real-world cohort of IBD patients, we found no difference in pharmacokinetics between reponders and non-reponders to ustekinumab.
P475 Real world data on treatment success and drug persistence in anti-TNF therapy for ulcerative colitis
Authors: Lundekvam J A , Høivik M L , Anisdahl K , Moum B , Medhus A W 
Published: May 2021

Abstract

Background
The efficacy and safety of anti-TNF treatment for ulcerative colitis (UC) have been well documented in clinical trials. More data are required to increase knowledge on treatment success in a real world setting. This study reports real world data on treatment success, drug persistence and safety of anti-TNF treatment in patients with UC.

Methods
Patients with UC starting anti-TNF treatment with infliximab (IFX) or adalimumab (ADA) between January 2014 and December 2019 at Oslo University Hospital in Norway were included in a retrospective review of medical records. Eligible patients were biologically naïve adults (≥18 years) with no history of UC-related surgery. Follow-up was 12 months. Drug persistence was defined as the proportion of patients still receiving first-line anti-TNF treatment without addition of a second biologic agent. Remission was defined as i) clinical remission (six-point Mayo Score &lt;2), ii) biochemical remission (fecal calprotectin &lt;250 and CRP &lt;5) or iii) a combination of the two. Treatment success was defined as drug persistence and remission. Serious adverse events (SAEs) were defined according to Good Clinical Practice guidelines.

Results
In total, 116 patients were included (mean age 35.5 ±13.9 years (SD), 58% male), of which 95 received IFX treatment and 21 ADA. Drug persistence was 74%. Treatment success by different definitions of remission and remission rates for drug persistent patients according to these definitions are reported in the table. SAEs were recorded on 18 occasions (four immediate infusion reactions, two colectomies, five infections and seven other events).

Conclusion
Treatment success by the strictest definition of remission was 40%. Of drug persistent patients, 44% were not in remission when applying the same definition. Whether these results reflect inadequacies in definitions of remission, a tendency for clinicians to let other variables guide treatment or a delay in drug switching warrants further investigation.
P507 Vulvar Crohn’s disease: A challenging diagnosis
Authors: Sahar N , Dahmani W , Nour E , Aya H , Wafa B A , Aida B S , Ahlem B , Mehdi K , Hanene J , Ali J 
Published: May 2021

Abstract

Background
Crohn’s disease is an inflammatory bowel disorder with several well-known extraintestinal manifestations, such as erythema nodosum, uveitis, and arthritis. Less commonly observed are cutaneous, so-called metastatic lesions of the vulva, which represent a diagnostic and therapeutic dilemma and require a multidisciplinary approach.
The objective of this study was to report a case series of patients with vulvar Crohn’s disease (VCD), describe its clinical features, histopathologic characteristics and therapeutic management.

Methods
In this retrospective study, we reviewed all cases of VCD seen in our department between 2008 and 2016. Data concerning age at diagnosis of VCD, vulval symptoms at presentation, histologic findings, and different treatment modalities were recorded. Only patients with both clinical features of VCD [knife-cut fissures, edema, ulceration] and histologic confirmation were included. A total of 3 cases were identified among 106 female patients with CD.

Results
Case 1: A 58-year-old patient, presented with a 4-year history of vulvar pain and itching. She had no bowel complaints. Clinical examination revealed hypertrophic exophytic lesions associated with linear ulcearations involving the vulva. A biopsy from the lesional skin showed non caseating gigantocellular granuloma. In view of the clinical and histopathological features, a diagnosis of Crohn’s disease of the vulva was made. Anti TNF treatment with adalimumab was started, resulting in a significant regression of the lesions.
Case 2: A 47-year-old patient presented to our department with complaints of painful, persisting vulvar ulcers, and resulting dysperunia for 2 years. On clinical examination she had unilateral vulvar oedema with multiple “knife-cut” linear ulcers. A skin biopsy was done which revealed dense inflammatory lymphocytic infiltrate with non caseating granulomas. Treatment with adalimumab was initiated. An improvement of symptoms was noted.
Case 3: A 16-year-old patient with no remarkable medical history, presented with a 2-year- history of persistent cheilitis and vulvar pain. Clinical examination of the external genitalia revealed ‘knife-cut’ vulvar fissures with important bilateral labial swelling and multiple papules on the surrounding skin. Histological analysis showed chronic inflammatory infiltrate with noncaseating tuberculoid granulomas. Anti-TNF treatment with infliximab was started with partial regression of lesions.

Conclusion
Our findings highlight the importance of keeping VCD on the differential diagnosis when faced with a range of vulvar symptoms. Anti-TNF agents seem to be an efficient treatment strategy for this particular localization.
P516 Serological biomarkers of tissue remodeling are associated with endoscopic remission in Crohn’s disease patients treated with GED-0301 (mongersen)
Authors: Mortensen J , Feagan B , Bay-Jensen A C , Karsdal M A , Horan G , Harris S , Usikin K 
Published: May 2021

Abstract

Background
In Crohn’s disease (CD) Smad7 is overexpressed in the intestinal mucosa, where it contributes to a sustained production of inflammatory cytokines, increased matrix metalloproteinase (MMP) activity and chronic inflammation through inhibition of the anti-inflammatory actions of TGF-beta. GED-0301, an anti-sense oligodeoxynucleaotide complementary to the mRNA of Smad7, inhibits the translation and synthesis of the Smad7 protein. We investigated exploratory biomarkers of collagen degradation by MMPs (C1M, C3M, C4M) and collagen formation (PRO-C3, PRO-C4 and PRO-C5) and their association with endoscopic remission in CD patients treated with GED-0301.

Methods
63 CD patients were randomized (1:1:1) to 4, 8 or 12 weeks oral, blinded GED-0301 160 mg daily (ClinicalTrials.gov no: NCT02367183). Simple endoscopic score for CD (SES-CD) (centrally read) was used to evaluate disease activity. Remission was defined as a SES-CD≤4 score at week 12. 54 CD patients completed the 12-week induction phase. Serum biomarkers measured by competitive ELISA se included C1M, C3M, C4M, PRO-C3, PRO-C4, PRO-C5 at baseline, week 4, week 8 and week 12. Spearman rho correlation was applied to evaluate the association with biomarkers and SES-CD score.

Results
Seven patients (11%) achieved a SES-CD≤4 at week 12. At baseline and at week 12 the biomarkers, C1M (baseline: r=0.36, P=0.005; wk12: r=0.47, P=0.0007), C3M (baseline: r=0.46, P=0.0002; wk12: r=0.28, P=0.047), C4M (baseline: r=0.40, P=0.002; wk12: r=0.36, P=0.011) PRO-C4 (baseline: r=0.36, P=0.004; wk12: r=0.35, P=0.013), and PRO-C5 (baseline: r=0.30, P=0.022) correlated with SES-CD (table 1). Remitters at baseline showed a numerically lower serum levels of C1M (54ng/mL vs. 65ng/mL), C3M (14.7ng/mL vs. 16.5ng/mL), PRO-C4 (241ng/mL vs. 299ng/mL) and PRO-C5 (442ng/mL vs. 660ng/mL) compared to non-remitters. The biomarkers C1M (P&lt;0.05), C4M (P&lt;0.05) and PRO-C5 (P&lt;0.05) were significantly suppressed in remitters at week 12 compared to non-remitters (figure 1). The same biomarkers also demonstrated sustained suppression of serum concentrations at week 4, 8 and 12 (C1M: 21.6% decrease from baseline at week 12; C4M: 15% decrease from baseline at week 12; PRO-C5: 26.6% decrease from baseline at week 12) in remitters compared to non-remitters.

Conclusion
Biomarkers of tissue remodeling correlated with the SES-CD scores of CD patients treated with mongersen. Patients s who achieved remission based on endoscopic criteria showing greater suppression of these biomarkers relative to non-remitters. Collectively, these data suggest that biomarkers of tissue remodeling may be useful to monitoring disease activity and mucosal changes in CD patients.
P622 Comparison of midterm outcomes in Pediatric Crohn’s Disease patients treated with either Exclusive Enteral Nutrition or Corticosteroids around disease diagnosis– a population based study
Authors: Plotkin L , Focht G , Harel S , Dotan I , Greenfeld S , Kariv R , Gabay H , Loewenberg Weisband Y , Turner D 
Published: May 2021

Abstract

Background
Corticosteroids (CS) and exclusive enteral nutrition (EEN) are commonly used as induction therapy in pediatric Crohn’s disease (PCD). Pediatric studies showed that CS treatment is equivalent to EEN for induction of remission, and it is easier to tolerate. However, EEN may be associated with superior long-term outcomes but this remains controversial. We thus aimed in this population-based study to compare CS dependency rate in children receiving EEN vs CS as induction therapy at the time of diagnosis, and to explore additional outcomes after one and two years of follow-up: IBD-related surgery, hospitalizations, and the use of biologics.

Methods
This study was performed on data from two Israeli Health Maintenance Organizations (HMOs), covering 78% of the population. We included all PCD patients (&lt;18 years) diagnosed between 2005 and 2017 treated with EEN or CS within the first six months of diagnosis, with at least one-year follow-up. We excluded patients who initiated biologics within the same quarter. CS dependency was defined as a systemic steroid course lasting &gt;90 days or four purchases with 12 months.

Results
A total of 2,730 PCD were identified, of whom 669 (24.5%) received induction therapy with either EEN [n=227 (8.3%)] or CS ([n=442 (16.2%)]. Median age at diagnosis was 13.04 years (3.8). Baseline (BL) characteristics, including age at diagnosis, anthropometrics data and gender, were similar between the groups.
Steroid dependency was higher in the CS group compared to the EEN group during the 1st and the 2nd year (10% vs. 7%, p&lt;0.001 and 14% vs. 12%, p&lt;0.001 respectively). Use of biologics was higher in the 1st but not the 2nd year in the EEN group compared to the CS group (28% vs. 19%, p=0.0016 and 40% vs. 33%, p=0.066 respectively). Hospitalization rate was higher in the CS group in both the 1st and 2nd years (42% vs. 22%, p&lt;0.001 and 51% vs. 30%, p&lt;0.001 respectively). There were no differences between the groups in surgeries rate and growth during the 1st and 2nd year follow-ups.

Conclusion
The use of CS as induction therapy in PCD was associated with a higher corticosteroid dependency rate, as well as more hospitalizations during the first two years of follow-up.
P631 Food triggers in inflammatory bowel disease from the patients’ and doctors’ perspective
Authors: Cappello M , Guida L , Di Giorgio F M , Busacca A , Carrozza L , Ciminnisi S , Almasio P L 
Published: May 2021

Abstract

Background
Diet is receiving growing attention as a key environmental factor involved in the pathogenesis of Inflammatory Bowel Disease (IBD). Dietary components have a relevant role in triggering symptoms from the patients’perspective, but there is a gap between patients’ and doctors’ beliefs. Every patient has collected his or her own list of prohibited foods and reports a clinical benefit from avoiding such foods. Elimination of nutrients can lead to nutritional deficiencies and impact on style and quality of life. The aim of this study is to identify frequently avoided foods in a Mediterranean cohort of patients with IBD.

Methods
Consecutive patients with IBD attending our tertiary center for infusion of biologics or for follow-up visits were enrolled. Demographics and disease characteristics UC or CD) were recorded in a dedicated database. A questionnaire investigated food avoided and reasons for dietary changes, if self-driven or advised by doctors or other healthcare professionals.

Results
167 patients agreed to participate in the study. Eighty-one patients (48.8%) had UC, 86 (51.5%) had CD. Mean age was 48.6 ± 16 (range 18–77 years), 57.5% were males. Patients were in clinical remission or with mild activity. Most patients, about 80%, and especially patients with CD avoided certain foods considered as triggers, and this avoidance was usually practiced in both exacerbations of the disease and remission periods. This occurred upon medical advice in a minority of patients, especially for vegetable avoidance (13.2%). Foods more frequently avoided were spicy foods, seasoned foods, fried foods, milk and dairy products, carbonated drinks, spirits, vegetables, legumes, and whole grain bread. Processed meat was avoided in about 6.6% (only in 1.8% upon medical advice) and coffee in 12.6%. A lactose-free diet was advised by the treating physicians only in 14.3% of patients. 4 patients were on a glutenfree diet because of a self-reported gluten sensitivity. The role of other healthcare professionals (dietitician, nurses) was marginal in their food choices.

Conclusion
Most of the patients set diet on self-experience and give up many foods. Our results are comparable with those of previous studies. Spicy foods, seasoned and fried foods, carbonated drinks, and dairy products are on top of the list. Legumes and vegetables, the cornerstones of the Mediterranean diet, are also avoided even though the evidence that dietary fibers can induce relapse is lacking. The benefit reported could be related to the effect on IBS-related symptoms frequent in IBD in remission. Further studies and a greater involvement of doctors in providing dietary recommendations are warranted.