bluuebunny/crossref_metadata_2025_split huggingface dataset:
P703 Addition of azathioprine to switch of anti-TNF in patients with IBD in clinical relapse with pharacokinetic failure: A post hoc analysis of a prospective randomised trial using drug-tolerant assay
Authors: Paul S , Williet N , Nancey S , Veyrard P , Boschetti G , Berger A E , Flourie B , Peyrin Biroulet L , Roblin X 
Published: January 2020

Abstract

Background
In a recent prospective, randomised trial, we showed that the rates of clinical failure and occurrence of unfavourable pharmacokinetics using a drug-sensitive assay after a switch of anti-TNF were significantly higher in monotherapy compared with combination therapy (Log-rank test p &lt; 0.0001), whatever the anti-TNF used in IBD patients. We aimed in a post hoc analysis to assess the time-course of antidrug antibodies in the two groups of patients using a drug-tolerant assay previously described (1).

Methods
After switching of anti-TNF under mono or combotherapy, blood samples were uptake at various time-points (6, 12, 18 and 24 months). Using a drug-tolerant assay, we defined pharmacokinetic failure when antidrug antibodies were detected (&gt; 2.5 μg/ml Eq). Transient anti-drug antibodies were defined as antibodies that appeared during the course of anti-TNF therapy with no clinical worsening, and finally that disappeared after 2 consecutive measurements.

Results
Ninety patients were analysed. According to a drug-tolerant assay, the occurrence of antibodies against anti-TNF was significantly higher in patients under monotherapy (log-rank test p &lt; 0.0001 (HR = 3.36 [1.94–5.86]) than under combination therapy. The rates of anti-drug antibody were significantly lower under IFX-AZA combotherapy compared with ADA-AZA combotherapy or under monotherapy. Monotherapy ADA (HR = 5.55[2.46–12.34]) or IFX (HR = 6.05[2.67–13.70]) and combination therapy ADA-AZA (HR = 3.34 [1.407.98]) increased significantly the rates of pharmacokinetic failure using a drug-tolerant assay compared with IFX-AZA combotherapy. The time-course without pharmacokinetic failure was significantly different between the 4 groups of patients from 15 months (p = 0.04) but was not significantly different at 6 months (p = 0.12). Overall, 9% of patients developed transient antibodies. Detection of antibodies against anti-TNF at 6 months using a drug-tolerant assay predicted significantly an immunogenic failure assessed previously by a drug-sensitive assay with a sensitivity of 57.1%, a specificity of 92.7%, a positive predictive value of 90.3%. In contrary to the association between clinical failure and immunogenic failure using drug-sensitive assay, the association of detectable drug and positive antibodies using a drug-tolerant assay was not significantly associated with clinical failure (HR = 1.3[0.3–6.8], p = 0.51).

Conclusion
Pharmacokinetic failure using a drug-tolerant assay was significantly lower under combotherapy, especially for IFX-AZA. Detection of anti-drug antibodies could predict pharmacokinetic failure.

Reference
P705 Dietary practices and beliefs of patients with older-onset inflammatory bowel disease: A prospective UK study
Authors: Crooks B , McLaughlin J , Limdi J K 
Published: January 2020

Abstract

Background
In an aging population, 25–35% of those with inflammatory bowel disease (IBD) are over 60 years old. A third of these are diagnosed at or over the age of 60 (older-onset IBD). Virtually no studies exist exploring the dietary practices and beliefs of patients with older-onset IBD. Elderly patients with IBD are at increased risk of nutritional deficiency and associated complications making it all the more important to understand the dietary habits and self-imposed restrictions of this group.

Methods
A prospective, cross-sectional, questionnaire-based study is being conducted across NHS Trusts within the UK. Two-hundred patients with older-onset IBD will be recruited to complete a questionnaire regarding demographics and dietary practices. Here we provide an interim analysis of the data collected from the first 75 patients.

Results
Mean patient age is 73 years, 51% are male and 95% Caucasian. 68% have ulcerative colitis. Mean disease duration is 6 years. Thirty-six per cent of patients believe diet was an initiating factor in their IBD and this is based on their own experience (78%) or advice from a gastroenterologist (33%), dietitian (22%) or GP (22%). Fifty-six per cent of patients report a disease relapse in the last year and just under a third believe that diet could trigger a relapse. The most commonly identified triggers are spicy foods (61%), raw fruit and vegetables (57%), fatty foods (39%) and milk products (30%). Sixty-three per cent of patients avoid certain foods to prevent a relapse of IBD. The most commonly avoided foods are spicy (81%) and fatty foods (66%), carbonated drinks (60%), red meat (53%), raw fruit and vegetables (49%) and alcohol (49%). Half of patients report being able to find specific advice regarding dietary recommendations in IBD and 72% of these obtain this information from the internet. A quarter of patients avoid eating the same menu as their family at least some of the time to prevent relapse of their IBD and 36% of patients avoid eating out. One in five patients has tried a specific exclusionary diet to help manage their symptoms, most commonly a gluten free diet, in the absence of coeliac disease, in 12% of patients.

Conclusion
Despite a relatively low proportion of older-onset IBD patients believing diet is implicated in the initiation of their disease or its relapse, a significant number continue to restrict their diet. This, along with co-existing frailty, comorbidities and polypharmacy, may put this group of patients at increased risk of nutritional deficiency and its associated complications as well as impacting upon quality of life. Improved knowledge of the dietary habits of those with ‘older-onset’ IBD will allow healthcare professionals to identify those at risk and offer appropriate dietary interventions.
P711 Carriage of the HLA-DQA1*05 allele is associated with a high risk of loss of response to adalimumab in patients with Crohn’s disease
Authors: Guardiola Capón J , SERRA K , Rodríguez-Alonso L , Santacana E , Padró A , Padullés N , Ruiz-Cerulla A , Arajol C , Camps B , Surís G , Orobitg J , Rodríguez-Moranta F 
Published: January 2020

Abstract

Background
Loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) occurs in up to 50% of patients with inflammatory bowel disease (IBD). The ability to predict which patients are likely to lose response would allow therapies to be tailored to the patient’s characteristics. Immunogenicity is a common cause of LOR. Recently, a GWAS performed using the PANTS cohort demonstrated that carriage of one or more HLA-DQA1*05 alleles confers an increased risk of immunogenicity to anti-TNF therapy (Sazonovs et al. Gastroenterology 2019). We found that HLA-DQA1*05 carriage also identified patients at increased risk of clinical LOR to infliximab (Guardiola et al. ECCO 2019). The aim of our study was to know if carriage of a HLA-DQA1*05 allele is also associated with secondary LOR to adalimumab (ADA) in patients with Crohn’s disease (CD).

Methods
This is a retrospective cohort study from a prospectively maintained data base. Patients were included if they had achieved response to ADA. LOR was defined as recurrence or worsening of IBD-related symptoms that required a change or intensification in treatment, hospitalisation or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression.

Results
We included 53 patients with Crohn’s disease, followed up to LOR (n = 31, 58%) or a median of 51 months (IQR 35–74). Forty-five per cent were carriers of an HLA-QA1*05 allele. HLA-DQA1*05 carriage was associated with LOR both, upon univariate analysis (HR 2.1 (95% CI 1.1–4.3), p = 0.04) and upon multivariate analysis, after adjusting for immunomodulators use, smoking status and BMI (HR 2.74 (95% CI 1.2–6.2), p = 0.02) (Figure 1). The cumulative persistence rates of ADA after adjusting for immunomodulators use was significantly lower in HLA-DQA1*05 carriers compared with non-carriers (HR 4 (95% CI 1.2–15.5), p = 0.02) (Figure 2).

Conclusion
HLA-DQA1*05 carriage is frequent and it is associated with a marked increase in the risk of LOR to ADA. HLA-DQA1*05 may become a clinically meaningful genetic marker that could allow for treatment to be tailored according to the risk of LOR, which is a step towards personalised medicine.
P712 Association of histologic-endoscopic mucosal healing after ustekinumab induction or maintenance therapy with 2-year outcomes in the UNIFI Phase 3 study in ulcerative colitis
Authors: Li K , Yang F , Marano C , Zhang H , Sandborn W J , Sands B E , Feagan B G , Rubin D T , Peyrin-Biroulet L , Friendman J R , De Hertogh G 
Published: January 2020

Abstract

Background
Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC). Histological and endoscopic improvement of mucosa after induction are associated with clinical remission and steroid-free clinical remission at maintenance Week 44. The association of histological-endoscopic mucosal healing after UST induction or maintenance therapy with 2-year outcomes in moderate-to-severe UC is not known.

Methods
In the UNIFI study of UST in moderate-to-severe UC, histological-endoscopic mucosal healing was defined as achieving both endoscopic improvement (Mayo endoscopy subscore ≤1) and histological improvement (i.e., neutrophil infiltration in &lt;5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on the Geboes score). Associations of mucosal improvement after induction (irrespective of treatment) or UST maintenance with long-term efficacy of UST, disease severity, inflammation level, and dose adjustment were evaluated up to Week 92 in the long-term extension (LTE) phase of UNIFI. Analysis was conducted in patients who were randomised to receive UST maintenance therapy and continued with UST in LTE. Tests with p-value &lt;0.05 were considered statistically significant.

Results
Patients with histological-endoscopic mucosal healing after induction had significantly lower disease activity (partial Mayo score and stool frequency) and a trend for lower inflammation measured by CRP and faecal calprotectin at maintenance Week 44 than those without induction mucosal healing (Table 1). These improvements in disease activity were retained through LTE Week 92, with patients with induction histological-endoscopic mucosal healing showing a continuous reduction of disease activity. Significantly lower disease activity, CRP, and faecal calprotectin were also observed through LTE among patients with histological-endoscopic mucosal healing after UST maintenance compared with those without (Table 1). Patients with histological-endoscopic mucosal healing after induction remained on treatment longer than those without (p &lt; 0.05). In addition, patients with histological-endoscopic mucosal healing after induction or maintenance were less likely to receive dose adjustment during LTE, but this association was not statistically significant.

Conclusion
Early macroscopic and microscopic improvement of the mucosa is an indicator of positive long-term clinical outcomes and reductions in inflammatory burden.
P718 Combination therapy of adalimumab with an immunomodulator is not more effective than adalimumab monotherapy in children with Crohn’s disease
Authors: Matar M , Shamir R , Turner D , Broide E , Weiss B , Ledder O , Guz-Mark A , Rinawi F , Cohen S , Topf Olivestone C , Shaul R , Ben-Horin S , Assa A 
Published: January 2020

Abstract

Background
The PAILOT trial was a randomised controlled trial aimed to evaluate proactive vs. reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim, in this post-hoc analysis of the PAILOT trial, was to assess the efficacy and safety of adalimumab combination treatment in comparison to monotherapy at week 72 after adalimumab induction.

Methods
Participants were children 6–17 years old, biologic naïve, with moderate-to-severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline, maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit patients were assessed for disease index, serum biomarkers, faecal calprotectin, adalimumab trough concentration and anti-adalimumab antibodies.

Results
Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period there was no significant difference in the rates of sustained corticosteroid free clinical remission (25/34, 73% vs. 28/44, 63%; p = 0.35), and sustained composite outcome of clinical remission, CRP≤0.5 mg/dl and calprotectin≤150 µgr/gr (10/34, 29% vs. 14/44, 32%; p = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive sub-groups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but numerically higher in the monotherapy group.

Conclusion
Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD.
P721 Early vedolizumab trough levels are associated with induction therapy outcome
Authors: O’Connell J , Corcoran R , Argue R , McDonagh P , Ismail M S , Cullen G , Doherty G , Hartery K , Healy M , McCormack M , MacCarthy F , McKiernan S , O’Connor A , Ryan B , McNamara D , Kevans D 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) is a monoclonal antibody which targets a4b7 integrin. It has been demonstrated to have efficacy in the induction and maintenance of remission in patients with both ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to determine factors, including drug levels, associated with success of VDZ induction therapy.

Methods
Patients were recruited prospectively from three Irish Academic Medical Centres. Individuals were included if &gt;18 years, with an established diagnosis of UC or CD and due to commence VDZ therapy. Disease activity scores were assessed on day of infusion (week 0) and again at week 14. All patients received standard per protocol VDZ induction therapy for UC and CD. Serum samples for trough VDZ level assessment were collected prior to week 2 and 6 VDZ infusions. The primary endpoint was steroid-free remission following VDZ induction assessed at week 14. Steroid free remission was defined as the absence of corticosteroid use and a partial mayo score ≤ 1 (for UC patients) or HBI &lt; 5 (for CD patients). All continuous data are presented as median (range). p-value of &lt;0.05 was considered significant in all analyses.

Results
Forty-four patients were recruited of whom n = 40 had available follow-up to week 14 [median age at study entry was 51.95 (18.2–75.8); 55% of cohort had CD]. Concomitant immunomodulator use and corticosteroid use at VDZ initiation was 22% and 20% respectively. 70% had prior biologic exposure. Baseline partial Mayo score at study entry was 4 (2––6) while baseline HBI was 7 (1––20). Baseline CRP was 3.6 mg / L (1––43), albumin 41 g / L (30––52) and faecal calprotectin 764 (16.4––1250). Week 2 and week 6 trough VDZ concentrations were 25.1 μg/ml (0––56) and 20.2 μg/ml (0––66), respectively. Eighteen patients (45%) were in steroid free remission after induction at week 14. There was an association between increased week 6 trough VDZ levels and steroid free remission at week 14, p = 0.015. There was no association between week 2 trough VDZ levels and therapy outcome. Receiver operating characteristics curve was plotted for Week 6 VDZ levels with the area under the curve (95% confidence interval) being 0.742 (0.572––0.912). A cut off VDZ level of &lt;16.7 µg/ml gave a sensitivity of 80% and specificity of 63%. An elevated baseline CRP (&gt;5mg/L) was significantly associated with and absence of steroid free remission at week 14, p = 0.001.

Conclusion
Early vedolizumab trough levels are associated with steroid free remission following induction therapy. Vedolizumab therapeutic monitoring may have value in a clinical setting, however, further prospective studies and clinical validation is required.
P725 Trends in biologic use prior to resective surgery for inflammatory bowel disease: A Canadian population-based study
Authors: Chopra D , Kennedy E , Weizman A V , Tennakoon A , Targownik L E 
Published: January 2020

Abstract

Background
Despite advances in medical therapy for inflammatory bowel disease (IBD), surgery is required in 50–80% of patients with Crohn’s disease (CD) and 20–30% of patients with ulcerative colitis (UC). Given that fibrostenotic disease may be playing a primary role in patients undergoing resective surgery, practices around biologic administration in this setting need to be clarified. We aimed to describe the pre-operative trends in biologic utilisation for IBD patients undergoing resective surgery.

Methods
The University of Manitoba IBD Epidemiology Database was used to identify all persons with IBD who underwent resective surgery between April 2005 and 2018. Demographic data were extracted to explore the baseline characteristics of persons on biologic therapy prior to IBD resective surgery. Proportion calculations were used to assess how often a new biologic agent was initiated within 3, 6, and 12 months prior to resective surgery. Results were stratified by type of IBD (UC vs. CD) and disease duration (&lt;3 or ≥3 years) for incident cases.

Results
A total of 1412 IBD-related resective surgeries were identified from April 2005 to 2018. 67.1% of resective surgeries were performed for CD and 32.9% for UC. Results of analysis are presented below:

Conclusion
Overall, in Manitoba, rates of biologic initiation or re-start in the pre-operative period for IBD resective surgery are relatively small. Biologic therapy was initiated or re-started more frequently for CD than UC, and when disease duration was less than 3 years. This is reassuring and suggests that physicians are rarely choosing to initiate biologic therapy in futile situations. Work should be performed to see if these findings can be replicated in other practice settings.
P729 The SAPPHIRE registry: Safety of immunosuppression in a prospective cohort of inflammatory bowel disease patients with a HIstoRy of CancEr
Authors: Axelrad J , Colombel J F , Scherl E , Lukin D , Chang S , Chen L , Kwah J , Swaminath A , Sultan K , Lawlor G , Villagra C , Galanko J , Sharpless V , Itzkowitz S 
Published: January 2020

Abstract

Background
Previous retrospective studies have demonstrated that patients with inflammatory bowel disease (IBD) exposed to anti-TNF and/or immunomodulators (IMM) following a diagnosis of cancer were not at an increased risk of new or recurrent cancer compared with those unexposed to these agents. Prospective studies are lacking and little is known about cancer risk with ustekinumab and vedolizumab. The SAPPHIRE Registry was developed to prospectively examine whether patients with IBD and a history of cancer subsequently exposed to immunosuppressive IBD therapies are at greater risk of new or recurrent cancer compared with those not exposed to immunosuppression.

Methods
We are longitudinally following patients with IBD and a histologically confirmed first cancer within the last five years from 8 centres affiliated with the New York Crohn’s and Colitis Organization (NYCCO) between 2017 and 2019. Patients receiving chemotherapy or radiation at enrolment, a first cancer more than 5 years prior to study entry, or recurrent cancer within the last 5 years are excluded. Cancers are categorised into luminal gastrointestinal (GI), hematologic, dermatologic, and other solid malignancies. Our primary outcome is the development of new or recurrent cancer stratified by immunosuppression exposure.

Results
We identified 170 patients with IBD and a history of a first cancer within the last 5 years (Table 1). The average age at IBD diagnosis was 36 years; average age at cancer diagnosis was 54 years. Patients were 49% male, 91% white, and 39% former smokers. Prior cancers were solid (78; 46%), GI (23; 14%), dermatologic (59; 35%), and hematologic (12; 7%) malignancies. Following a diagnosis of cancer, patients were exposed to IMM (38; 22%), anti-TNF (45; 26%), vedolizumab (41; 23%), ustekinumab (17; 10%), or no immunosuppression (33; 19%; Table 2). During follow-up, 13 (8%) patients developed 14 subsequent cancers (6 new, 8 recurrent) comprising 6 (43%) solid, 1 (7%) gastrointestinal, and 7 (50%) dermatologic malignancies. Compared to patients not exposed to immunosuppression, exposure to an IMM (RR 4.94, 95% CI 0.50, 48.6) or a biologic (RR 3.53, 95% CI 0.71, 17.5) was not associated with an increased risk of new or recurrent cancer. However, exposure to combination therapy with an IMM and a biologic (RR 6.81, 95% CI 1.40, 33.2) was associated with an increased risk in this small sample.

Conclusion
In this ongoing prospective study, exposure to immunosuppressive IBD monotherapies in patients with IBD and a recent history of cancer has so far conferred no increased risk of new or recurrent cancer. Continued enrolment will enable a more refined estimate of the safety of combination therapies.