bluuebunny/crossref_metadata_2025 huggingface dataset:
P687 Early and sustained improvement in stool frequency and rectal bleeding following 52 weeks of mirikizumab treatment
Authors: D’Haens G R , Hibi T , Ferrante M , Bhandari B R , Berliba E , Tuttle J L , Lissoos T , Krueger K , Morris N , Arora V , Naegeli A N , Feagan B G
Published: January 2020

Background

Interleukin (IL)-23 is a key cytokine in inflammatory bowel disease pathogenesis. Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in patients with moderate-to-severely active ulcerative colitis (UC) during 52 weeks of a Phase 2 randomised clinical trial (AMAC, NCT02589665). The effects of miri on stool frequency (SF) and rectal bleeding (RB) through Week 52 are reported.

Methods

Patients (Mayo score 6–12 with endoscopic subscore [ES] ≥2) were randomised 1:1:1:1 to receive intravenous (IV) placebo (n = 63), miri 50 mg (n = 63) or 200 mg (n = 62) with possibility of exposure-based (EB) dose increases, or fixed miri 600 mg (n = 61) every 4 weeks (Q4W). Responders to miri at Week 12 (9-point Mayo score decrease ≥2 points and ≥35% change from baseline, with RB=0 or 1 or decrease ≥1) were re-randomised 1:1 into a double-blind maintenance period to receive miri 200 mg subcutaneously (SC) Q4W (n = 47) or every 12 weeks (Q12W; n = 46), and were treated through Week 52. Patients reported UC symptoms, including SF and RB, via a daily diary. Changes from baseline in average Mayo SF and RB subscores at Weeks 2, 4, and 12 were analysed using a mixed model repeated-measures method to account for missingness and baseline characteristics.

Results

Significant improvement in SF was observed as early as Week 2 in the miri 600 mg Q4W group and as early as Week 4 in the miri 200 mg Q4W group (Figure). Similarly, significant improvement in RB was observed as early as Week 2 in both the miri 200 mg Q4W and 600 mg Q4W groups. Patients who received miri 200 mg Q4W or 600 mg Q4W had a significantly greater reduction in both SF and RB compared with placebo at Week 12 (all p < 0.001) (Figure). Patients who achieved clinical response at Week 12 and were treated with miri 200 mg SC Q4W or SC Q12W maintained a low average SF and RB score at Week 52.

Conclusion

Significant improvements in SF and RB occurred as early as Week 2 of induction treatment and continued to improve during maintenance treatment with mirikizumab. These data demonstrate the early efficacy and longer-term effects of an IL-23p19 antibody on these patient-reported outcomes.
P689 Patient-reported outcomes (PRO-2) and intestinal ultrasound in ulcerative colitis patients: subanalysis of the TRUST&UC study cohort
Authors: Maaser C , Helwig U , Fischer I , Rath S , Kolterer S , Kucharzik T
Published: January 2020

Background

Patient-reported Outcomes (PRO) are gaining increasing acceptance as new tools to evaluate clinical activity, especially in the context of clinical trials and evaluation of drug efficacy. However, data to support the relevance of these endpoints and their correlation to objective markers of inflammation is still lacking.1 Recently published data demonstrated the feasibility of intestinal ultrasound (IUS) as a routine monitoring technique in clinical practice for Crohn’s disease (CD) and ulcerative colitis (UC) patients.2 Thus, the importance and significance of IUS, as a patient-centric and non-invasive technique has emerged over the last years and will become more relevant in the future.With this sub-analysis of the TRUST&UC study, we aimed to investigate the correlation between improvement in ultrasound parameters and PRO-2 in UC patients.

Methods

TRUST&UC is a prospective, observational study including 244 patients with an increased bowel wall thickness (BWT) at baseline and active UC (SCCAI ≥ 5). These patients were analysed for the Simple Clinical Colitis Activity Index (SCCAI) subscores stool frequency, urgency and rectal bleeding. These parameters were documented for up to 4 visits (baseline, an optional visit at week 2, week 6 and week 12). Pathological stool frequency was defined as a stool frequency of ≥1 point (≥ 4 stools/day) and pathological rectal bleeding was defined as ≥1 point (traces of blood in stool); the combination of both subscores was defined as PRO-2.

Results

We found a positive moderate correlation between BWT and the investigated SCCAI-subscores (rectal bleeding and BWT at W12 r = 0.417; stool frequency and BWT at W12, r = 0.483; PRO-2 and BWT at W12, r = 0.518) and even W6, which is in accordance with previously reported correlations of various PROs and endoscopy in UC-patients.3 We demonstrate that patients with normalisation of BWT (sigmoid colon < 4.0 mm) had a significantly higher chance of a non-pathological PRO-2 (pathological PRO-2 yes/no: 4.25 mm and 3.20 mm for week 6 (p < 0.001) and 4.45 mm and 3.00 mm (p < 0.001) for week 12).

Conclusion

With this sub-analysis of the TRUST&UC study we demonstrated that bowel wall thickness, assessed by intestinal ultrasound, had a moderate correlation with normalisation of patient-reported outcomes as early as week 6 and 12. Furthermore, patients with non-pathological PRO-2 had significantly decreased bowel wall thickness. This again supports the value of intestinal ultrasound in routine medical practice.

References
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

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 < 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 (> 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 < 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

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

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

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 <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 <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 < 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

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

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 >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 < 5 (for CD patients). All continuous data are presented as median (range). p-value of <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 <16.7 µg/ml gave a sensitivity of 80% and specificity of 63%. An elevated baseline CRP (>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

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 (<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

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.
P731 Biologics use in elderly patients with IBD: Experience in a UK secondary care setting
Authors: Alexakis C , Robinson J , Yeates R , Ho-Yen N , Mathew S , Gallagher M , Banks C , Alexandropoulou K
Published: January 2020

Background

The combination of an ageing population coupled with a rising incidence in inflammatory bowel disease (IBD) will undoubtedly result in increased use of biologic agents in older patients with IBD, yet long-term data on the use of these drugs in this population remains scarce. We describe our experience of biologic treatment in IBD patients aged 60 years or greater at a UK district general hospital.

Methods

This was a retrospective descriptive study performed at Royal Surrey NHS Foundation Trust which serves a population of 300,000 people. IBD patients on biologic therapy are all registered on a prospectively collated database. Patients were included in this study if their biologic start date was on or after their 60th birthday. Each patient had their clinical records assessed and the following baseline data were recorded: sex, IBD subtype, concurrent medication use, relevant medical history and co-morbid status (using the Charleston Morbidity Index (CMI)), age at biologic start date and biologic subtype. Patients were followed up from biologic start date to biologic end date, death or end of study period (01.07.2019). Kaplan Meier analysis was used to generate biologic survival or ‘persistence’. During follow-up, we recorded the incidence of both infective and non-infective complications, and the incidents of both IBD surgery and malignancy.

Results

Of 220 patients on biologic therapy, 19 (8.7%) were aged ≥60 years at initiation, of whom 18 had data included in the analysis including 431 patient-months of follow-up. 78% were male. Half of patients had Crohn’s disease. Median CMI was 4. Only 1 patient had a history of malignancy prior to biologic initiation. Mean age at biologic initiation was 69 years. 72% of patients were on concurrent immune suppression medication. Most patients (72%) were commenced on Infliximab (Adalimumab 17%, Vedolizumab 11%). Median biologic treatment time was 17 months. The 6, 12 and 24 month biologic persistence rates were 78%, 67% and 28% respectively. 22% of patients were subsequently treated with a second biologic. 17% required surgery despite biologic use. Over half (56%) of patients suffered a complication post first biologic initiation, the most frequent being infection which affected 44% of patients during follow-up. Where recorded or available, 41% of patients developed antibodies to biologic, with a mean time of 11.4 months treatment. There were no recorded malignancies in any patient following biologic initiation.

Conclusion

Just under one in 10 of our biologic cohort is above the age of 60 on commencement of therapy. Despite a heavy burden of infective complications, there is reasonable biologic persistence in this group, and importantly a negligible malignancy risk following treatment initiation.
P735 Comparative assessment of probiotics and standard therapies for mild to moderate ulcerative colitis: A systematic review and network meta-analysis
Authors: Paschos P , Katsoula A , Malandris K , Sarigianni M , Athanasiadou E , Koukoufiki A , Giouleme O , Tsapas A
Published: January 2020

Background

We performed a systematic review and network meta-analysis to compare probiotics to current therapies in the induction and maintenance of remission in ulcerative colitis (UC).

Methods

We systematically searched Medline, Embase, CENTRAL up to November 2018. We included randomised controlled trials (RCTs) in patients with mild to moderate UC that compared probiotics, sulfasalazine, mesalamine (low dose <2 g/day, standard dose ≥ 2 g/day), olsalazine, balsalazide, budesonide, budesonide MMX and beclomethasone either alone or in combination with topical therapy, to each other or placebo. We excluded trials where <50% of the population had extensive or left-sided colitis. Outcomes were remission (induction studies), relapse (maintenance studies) and discontinuation due to adverse events (tolerability). We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities.

Results

Forty-eight trials (probiotics 6 trials) of induction therapy and 30 trials (probiotics 6 trials) of maintenance therapy were included in the analysis. In studies with probiotics concomitant treatment, mainly mesalamine, were allowed. At induction, probiotics were not superior to placebo (OR 1.43; 95%CI 0.84–2.42) and they were inferior to combined oral and topical mesalamine therapy (OR 0.28; 95%CI 0.12–0.66) and combined mesalamine and beclomethasone therapy (OR 0.27; 95%CI 0.09–0.83). On SUCRA analysis, combination therapies (SUCRA 0.92 and 0.93) were ranked the highest followed by balsalazide (SUCRA 0.71), budesonide ΜΜΧ (SUCRA 0.68), standard dose mesalamine (SUCRA 0.52), beclomethasone (SUCRA 0.50), olsalazine (SUCRA 0.41), probiotics (SUCRA 0.29), low dose mesalamine (SUCRA 0.26) and sulfasalazine (SUCRA 0.23) in terms of inducing remission. Probiotics were well tolerated. At maintenance, probiotics (OR 0.35; 95%CI 0.19–0.62) and their combination with mesalamine (OR 0.38; 95%CI 0.15–0.99) had lower rate of relapse compared with placebo, but there were no differences when compared with other treatments. On SUCRA analysis, probiotics either alone or combined with mesalamine had comparable SUCRA values to standard dose mesalamine (SUCRA 0.59) and sulfasalazine (SUCRA 0.68). The combination of oral and rectal mesalamine was superior to placebo (OR 0.10; 95%CI 0.04–0.26) and all other treatments and it was ranked highest (SUCRA 0.99). Probiotics were ranked the best tolerated option in terms of discontinuation due to adverse events (SUCRA 0.80).

Conclusion

Probiotics are well tolerated but they are not effective in inducing remission in active UC. They may be effective when added to mesalamine therapy in preventing relapse of quiescent UC, but large, well-designed RCTs are needed.
P748 Characteristics of inflammatory bowel diseases in different stage of adolescence
Authors: Szántó K J , Bálint A , Bor R , Fábián A , Milassin Á , Rutka M , Szepes Z , Vass N , Molnár T , Farkas K
Published: January 2020

Background

There is a lack of data regarding clinical and therapeutic characteristics in middle and late adolescent inflammatory bowel diseases (IBD) patients in real life. Our aim was to retrospectively evaluate patient’s characteristics and therapeutic features among the Hungarian adolescent inflammatory bowel diseases population. Also our aim was to assess whether these patients before the transition have more serious disease phenotype than those after transition.

Methods

Retrospective, epidemiological study using the National Health Insurance Fund social security databases. Adolescent Hungarian IBD patients who were observable in the database between 2008 and 2017 were enrolled. Patients were analysed according to two groups: patients between ages of 14–17 years were defined middle adolescent patients, and patients between 18–21 years were defined late adolescent patients.

Results

The incidence of IBD was 24.82/100 000 in the middle and 38.17/100 000 in the late adolescent patients. Prevalence rates showed an increasing tendency in both groups. Incidence and prevalence rates were higher in the late adolescent patients. Mesalazine was used in high proportion of patients (66.6% vs. 69.3% of the middle and late adolescent patients, respectively), also in UC and CD patients. While, the use of sulphasalazine (13.1% vs. 19.6%, respectively) and azathioprine (20.3% vs. 11%, respectively) was relatively low. The need of biologics was higher in the middle adolescence group (p < 0.001). Use of anti-TNF agents increased during the observational period in both groups (p < 0.001). Corticosteroid use was similar in both groups; a decreasing tendency was observed. Rate of hospital admissions to gastroenterology department was higher than to surgery department in both groups. The number of hospital admissions to gastroenterology (p < 0.001, p = 0.001) and surgery departments (p < 0.001 and p = 0.031) decreased significantly in both groups throughout the observational period.

Conclusion

We have analysed the data of huge number of adolescent patients diagnosed with IBD to get better overview on the clinical and treatment characteristics of patients in these sensitive age groups. Overall, the increasing use of anti-TNF therapy and decreasing tendency of corticosteroid use reflects significant changes and improvement in treatment paradigm not only in adult but paediatric care. The higher need of anti-TNF agents reflects that these adolescent patients before the transition have more severe disease phenotype.
P753 Elevation of liver enzymes in a large cohort of patients with inflammatory bowel disease
Authors: ATIA O , Turner D , Mendelovici A , Assa A , Mozer-Glassberg Y , Cahan A , Lederman N , Matz E , Dotan I , Shteyer E
Published: January 2020

Background

Elevation in liver enzymes (ELE) is often seen in patients with inflammatory bowel disease (IBD). The aim of this study is to assess the incidence, character, chronicity, degree, and etiology of ELE in within the validated epiIIRN cohort which includes all IBD patients in Israel (n = 45,074).

Methods

We current analysis was performed on data from three of four Health Maintenance Organisations (HMOs), covering 48% of the Israeli population. The identification of Crohn’s disease (CD) and ulcerative colitis (UC) utilised previously validated algorithms. Retrieved data included demographics, anthropometric measures, liver enzymes, medications and other diagnoses codes. Mild ELE was defined from upper normal limit (UNL) to X2 UNL, moderate X3 UNL and severe elevation ≥X4 UNL). The pattern of elevation was defined as hepatocellular (isolated elevation of ALT and/or AST), cholestatic (elevated GGT and/or ALK and bilirubin) and mixed pattern. Chronicity of ELE was defined as brief (<30 days) to chronic (>180 days).

Results

The total incidence (ever) of ELE in CD patients was 33% (3098/9421) and 28% in UC (2001/7040); p < 0.001. The mean age at ELE was 29.9 years (IQR 17.2–47.5) in CD and 37.9 years (23.2–53.8) in UC (p < 0.001). Hepatocellular pattern had more commonly in UC (54% vs. 47%, p < 0.001) as mixed pattern (22% vs. 20%, p = 0.01), while cholestatic pattern had more commonly in CD (31% vs. 26%, p < 0.001). The ELE was transient in 609 (9%) patients, while 4054 (62%) had chronic ELE. Mild ELE was recorded in 860 (22%) CD patients and 460 (19%) UC, and severe in 328 (8%) CD and 253 (10%) UC. ELE was recorded during the first three months after initiation of thiopurines in 604 (15%) CD and 201 (8%) UC patients (p < 0.001), after biologics in 346 (9%) CD and 62 (3%) UC (p < 0.001), after steroids in 538 (14%) and 272 (11%), respectively (p = 0.01) and after methotrexate in 76 (2%) and 15 (0.6%), respectively (p = 0.001). The incidence of fatty liver was most common in UC (5% vs. 3%, p = 0.006).

Conclusion

ELE is common complication in IBD patients, more so in UC. When enzymes do increase in CD they tend to reach higher levels. Drug induced liver injury was more common in CD.

This study was supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust.
P758 Ileorectal anastomosis vs. ileal pouch-anal anastomosis for the surgical treatment of ulcerative colitis: A Markov decision analysis
Authors: De Buck Van Overstraeten A , Brar M , Khorasani S , Dossa F , Myrelid P
Published: January 2020

Background

Ileorectal anastomosis (IRA) in patients with ulcerative colitis (UC) results in decreased postoperative morbidity and better functional outcome but leads to increased risk for rectal cancer compared with ileal pouch-anal anastomosis (IPAA). This study aims to compare IRA with IPAA in UC, using decision analysis.

Methods

A Markov simulation model was designed to simulate clinical events of IRA and IPAA over a time horizon of 40 years with time cycles of 1 year (Figure 1). The base case was a 35-year-old patient with ulcerative colitis and relatively preserved rectum. Probabilities and utilities, required to populate the model, were derived from observational studies, identified after a systematic literature search using MEDLINE. Primary outcomes were life years (LY) and quality-adjusted life years (QALY). Deterministic sensitivity analyses were performed to assess the impact of changing variables on the preferred treatment. Monte Carlo probabilistic sensitivity analysis, using 10 000 samples, was performed to account for uncertainty of variables. Prevalence of rectal cancer, IPAA and IRA failure and the stoma rate were calculated at the end of the time horizon, using markov cohort analysis.

Results

The model resulted in lower LY (36.22 vs. 37.02) and higher QALYs (33.42 vs. 31.57) for IRA. The results of the Monte Carlo probabilistic sensitivity analysis demonstrated that IRA was the preferred treatment option in 63% of the samples, accounting for a clinical significant margin of 0.25 QALY (Figure 2). The model was also sensitive to the utility of IRA, IPAA and end-ileostomy. A higher proportion of IRA patients will develop rectal cancer (7.6% vs. 3.2%) and 43.5% of all IRA patients will end with an ileostomy as opposed to 23.0% of all IPAA patients. The study was limited by characteristics inherent to modeling studies, including assumptions necessary to build the model, data input based on best available but often limited evidence and unavoidable extra- and interpolation of data.

Conclusion

IRA was the preferred treatment option when quality-adjusted life years was the outcome, with higher life years for IPAA. This model highlights that both surgical strategies are useful in ulcerative colitis patients with relatively spared rectum.
P777
Clostridioides difficile infection in children with inflammatory bowel disease: A Canadian population-based study
Authors: El-Matary W , Chandrakumar A , Zohni H
Published: January 2020

Background

Toxigenic Clostridioides difficile (C. difficile), previously known as Clostridium difficile, is an anaerobic gram-positive spore-forming opportunistic pathogen associated with profuse diarrhoea and gastroenteritis associated mortality, especially in children with inflammatory bowel disease (IBD). The aim of this work was to investigate the incidence and risk factors associated with Clostridioides difficile infection (CDI) in children with IBD in the province of Manitoba, Canada.

Methods

Our longitudinal population-based cohort comprised of all children and young adults <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. Fisher’s exact test was used to examine the relationship between categorical variables. Cox-regression model was used to estimate the risk of CDI development in IBD patients.

Results

Among the 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years and the median age at diagnosis of 12.96 years (IQR: 9.33–15.81). The incidence rate of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (p = 0.46). Compared to children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (hazard ratio (HR) = 4.30; 95% CI: 1.44–12.87) and anti-tumour necrosis factor (TNF) biologics (HR = 3.37; 95% CI: 1.13–10.09). Recurrence rate of CDI in our paediatric IBD population was 25%.

Conclusion

Our findings confirm that children with IBD are at a high risk of developing CDI, which may predict future escalation of IBD therapy.
P781 Prevalence of antinuclear antibodies in inflammatory bowel disease and seroconversion after biological therapy
Authors: García García M J , Rodriguez-Duque J C , Arias Loste M T , Castro Senosiain B , Crespo J , Rivero M
Published: January 2020

Background

Higher levels of antinuclear antibodies (ANA) are detected in healthy populations with a prevalence of 6%. In autoimmune disorders it reaches 50–80%. In patients under TNF, the prevalence of positive ANA observed was 40% and occasionally may induce lupus like syndrome (LLS). However, there is a lack of evidence about the global prevalence in inflammatory bowel disease (IBD) and insufficient data about seroconversion of ANA after the beginning of biological therapy.

Methods

A unicentric transversal study of 879 IBD patients was designed. ANA determination was performed by immunofluorescence assay. IBD patients were classified according to the biological therapy. Presence and of ANA and titres were collected previously to the beginning of anti-TNF therapy. LLS symptoms were collected in a retrospective way.

Results

A valid result of ANA was obtained in 862 patients. Patients with any autoimmune disease which involve positive ANA were excluded. Positive ANA was reported in 13.62% of IBD patients. The prevalence of ANA was 28.67% in those patients under biological therapy (p < 0.001), especially if the biological treatment was anti-TNF. No significative difference was observed in those patients receiving ustekinumab or vedolizumab therapy. Positive ANA was observed in 4.67% for combined treatment with immunomodulator and biological therapy. In contrast, if the patient received only biological therapy, positive ANA was collected in 24 % (p < 0.001). A reduction in albumin levels and higher levels of IgG and IgM were related to positive ANA. It is important to highlight that a percentage of 53.45% positive ANA had never received biological therapy in the previous 5 years; that means, a 7.28% prevalence in the global cohort. A 48.15% of the patients had ANAs previous to the beginning of biological therapy. ANAs seroconversion was observed in 73.08% of the patients after the treatment.

Conclusion

IBD patients have a 13.62% prevalence of positive ANA; higher than prevalence in healthy population. The presence of ANA is frequently associated in patients under anti-TNF treatment and decreases with immunomodulator therapy associated to anti-TNF. It is unknown if positive ANA in IBD patients could be conditioned to the future development of other autoimmune disorders. Prospective studies are necessary to clarify these aspects.
P786 Non-alcoholic fatty liver disease among patients with inflammatory bowel disease in Qatar: Prevalence and risk factors
Authors: Almohannadi M , Chandra P , Varughese B , Darweesh A , Hamid A , Badi A , Kaabi S A , Yakoob R , Al-Ejji K , Sultan K , Abunahia N , Ameer Hamza Shah M , Derbala M
Published: January 2020

Background

Non-alcoholic fatty liver disease (NAFLD) has been progressively identified in patients with inflammatory bowel disease (IBD) in Qatar. We aim to characterise NAFLD in IBD patients in Qatar and to determine predictors for its severity.

Methods

A retrospective observational study was conducted on 913 IBD patients in Hamad hospital between January 2008 and December 2017. The prevalence of NAFLD among IBD cases was estimated and associations between two or more qualitative variables were assessed using χ2-test. Quantitative data between two independent groups were analysed using unpaired t-test. Univariate and multivariate logistic regression analysis were applied to determine the predictive values of each predictor for NAFLD among IBD patients.

Results

Among 913 IBD patients with a mean age of 36.9 ± 13.2 years and BMI 26.9 ± 6.1; 550 were males (60.2%), 383(41.9%) with Crohn’s disease and 530 (58.1%) with Ulcerative colitis. 24 (22.2%) patients had severe steatosis. The overall prevalence of NAFLD was 11.8% (95% CI 9.9, 14.1) and does not differ significantly between CD and UC patients (11.7% vs. 11.9%; p = 0.949). Patients who developed NAFLD were older at baseline, higher BMI and had a higher prevalence of diabetes and hypertension. Age >50 years (OR 3.34; 95% CI 1.82, 6.14; p = 0.001), BMI >30kg/m2 (OR 2.87; 95% CI 1.71, 4.84; p = 0.001), the presence of hypertension (OR 1.98; 95% CI 1.16, 3.38; p = 0.01) and diabetes mellitus (OR 3.05; 95% CI 1.87, 4.95; p = 0.001), were all positive and significantly associated with an increased risk whereas gender female associated with significantly decreased risk for NAFLD (OR 0.63; 95% CI 0.41, 0.98; p = 0.04). Multivariate analysis showed age >40 to 50 years (adjusted OR 2.98; 95% CI 1.62, 5.48; p = 0.001), age >50 years (adjusted OR 2.03; 95% CI 1.03, 4.0; p = 0.04), BMI>30 kg/m2 (adjusted OR 2.24; 95% CI 1.28, 3.91; p = 0.01) and diabetes mellitus (adjusted OR 1.98; 95% CI 1.15, 3.4; p = 0.02) significantly associated with an increased risk of NAFLD whereas gender female showed protective effect and have decreased risk (adjusted OR 0.58; 95% CI 0.36, 0.93; p=0.02). The treatment with biologic does not increase the risk of steatosis and the predicted cut-off NAFLD score of ≥ -1.67 had good predictive ability for significant steatosis.

Conclusion

The prevalence of NAFLD in IBD patients was 11.8% in Qatar. We did not find an association between the medications used and the progression to NAFLD in IBD patients. Older age, high BMI and diabetes mellitus increase its risk. Non-invasive screening using NAFLD Score could help early diagnosis and initiation of interventions in such patients.