bluuebunny/crossref_metadata_2025_split huggingface dataset:
P610 Optimising biological therapy in inflammatory bowel disease patients: the role of a virtual biological clinic
Authors: REES J , Maher C , Jones J , Slater J , Bates B , Rattehalli D , De Silva S 
Published: January 2020

Abstract

Background
The National Institute of Clinical Excellence (NICE) recommends that patients with inflammatory bowel disease (IBD) taking biologic agents are reassessed every 12 months, to determine whether continuation of therapy is appropriate. Only those with evidence of ongoing active disease, determined by clinical symptoms, biochemical markers, endoscopic or radiological investigations, should continue with therapy. With the increasing use of biologics, this represents a major challenge and may result in biologic agents being inappropriately continued, at significant cost to the NHS. A virtual biologics MDT (VMDT), consisting of 2 IBD consultants and 2 specialist nurses, was launched in 2017 at Russells Hall Hospital (RHH) to address this issue. We aim to evaluate its performance in 2018.

Methods
We performed a retrospective case note review of all patients discussed at the VMDT in 2018. Clinic letters, blood results, endoscopy reports and radiological investigations were examined to determine adherence to NICE guidelines.

Results
Out of a total 223 patients using biologics in 2018, 119 (51.2% male, 79.8% Crohn’s disease, mean age 42.7 years, 57.9% taking adalimumab) were discussed at the VMDT. 67/119 patients were taking a second immunosuppressant agent and out of the remaining 58, 32 had documented evidence of treatment failure or side effects on these agents and 23 were planned to commence them from the MDT. Fourteen patients (11.8%) had their biologic de-escalated post MDT and 5 (4.2%) were switched to a second-line agent. 1 patient’s planned de-escalation was prevented by ankylosing spondylitis. 26/119 patients had no recent or planned radiological or endoscopic reassessment of their disease at 12 months. Of these 26 patients, 17 had ongoing clinical symptoms preventing treatment withdrawal, 2 were de-escalated and 6 had plans to add a second agent prior to reassessment. Only 1 patient continuing treatment had a good indication for de-escalation. Of the 89 patients eligible for therapeutic drug monitoring, 8 were found to have no levels within 12 months of the VMDT (all taking adalimumab). All of these patients were identified at the time and 7 were sent for levels. The remaining patient had their drug discontinued.

Conclusion
The virtual biologics MDT at RHH has been shown to be an effective way of monitoring patients’ disease activity and drug levels, optimising drug therapy and appropriately de-escalating biologic agents. It was only possible to discuss 53.4% of our patients at the virtual MDT and we recommend this service is expanded by allocating a formal monthly session to ensure that all patients can be reviewed. Work is now underway to assess performance in 2019 and follow-up patients who have had their biologics discontinued.
P615 Safety of vedolizumab in the treatment of IBD in a single tertiary centre
Authors: Peruzzi G , Calandrini L , Privitera Hrustemovic H , Salice M , Decorato A , Carbone A , Rizzello F , Belluzzi A , Scaioli E , Calabrese C , Gionchetti P 
Published: January 2020

Abstract

Background
There is a lot of data on Vedolizumab efficacy in the treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD). Despite this, we have little real-world data on its adverse reactions. We aimed to identify and quantify principal adverse reactions in order to assess the safety of the drug.

Methods
UC and CD patients from a single tertiary IBD referral centre receiving Vedolizumab treatment between September 2016 and August 2019 were included. Data were collected prospectively at week 22, 54 and 108. Adverse events were categorised as infections, rheumatic/cutaneous disorders, allergy-related symptoms/anaphylactic shock, serious adverse events and drug discontinuation. Serious adverse events were those that resulted in hospitalisation or death. Discontinuation was due to drug-related effects or IBD complications that persisted despite the treatment or that could be worsened by drug-induced immunodepression.

Results
Our analysis comprised 200 patients (86 with UC and 114 with CD: 22% female; median age 58,3 years). Adverse effects were reported in 59/200 (29,5%) patients, leading to treatment discontinuation in 21/200 (10,5%) cases: 2 with UC and 19 with CD. Six patients experienced more the one adverse reaction for a total of 69. Rheumatic disorders were observed in 17/69 (24,6%), infections in 17/69 (24,6%) and cutaneous manifestations in 6/69 (8,7%). One patient complained of headache and another subocclusive symptom. One patient had an asymptomatic increase in cholestasis tests. No anaphylactic shock or allergy-related symptoms were reported while 6 patients (6/69, 8,7%) required hospitalisation (especially for infective complications). Vedolizumab discontinuation was due to perianal disease onset or relapse (9/21, 42,8%), infections (6/21, 28,6%) and rheumatic disorders (5/21, 23,8%); in one case we observed uncontrolled hypertension and Ménière syndrome. Treatment was restarted after surgical management and treatment with antibiotics in 3 patients with perianal disease and 1 with community-acquired pneumonia, respectively.

Conclusion
In our experience, Vedolizumab is a well-tolerated drug. Most of the adverse events that occurred in our centre were mild and did not require hospitalisation. In some patients discontinuation was not permanent: we performed it in order to treat the condition that contraindicated the administration and restart treatment.
P624 Maintenance of remission after treatment with Exclusive Enteral Nutrition and Azathioprine in paediatric patients with Crohn’s disease
Authors: Pujol Muncunill G , Pascual-Pérez A I , Dominguez-Sánchez P , Feo-Ortega S , Suárez-Galvis M , Vila-Miravet V , Martin de Carpi F J 
Published: January 2020

Abstract

Background
Several studies have shown the efficacy of Exclusive Enteral Nutrition (EEN) in patients with Crohn’s disease (CD) for the induction of remission. ECCO-ESPGHAN guidelines recommend the use of EEN combined with early use of immunosuppressants in paediatric patients with mild-to-moderate CD. However, there is a lack of data to show its efficacy in the long term to avoid or postpone the use of biological treatment. The aim of our study is to know how many of our patients that have achieved remission with EEN and Azathioprine (AZA), required to step up to biological treatment during the follow-up.

Methods
Retrospective analysis of paediatric patients with Crohn’s disease that were diagnosed at our Unit between 2003 and 2017. We included those patients that achieved clinical remission after treatment with EEN and AZA. We analyse demographics, clinical and follow-up data until February 2019 or until they are transferred to an adult inflammatory bowel disease (IBD) unit.

Results
We included 91 patients that achieved clinical remission after treatment with EEN and AZA (68.1% males; Mean age at diagnosis: 12.29 years; Median age at diagnosis: 13 years (range 8 months-17 years). The mean time of follow-up was 60.45 months (range: 8–165 months). During this period, 66/91 patients (72.5%), had a flare. Seventeen of those patients (20.2%) received a second cycle of EEN, being effective in 7 (41.2%). Mean time from diagnosis until the second cycle of EEN was 13.76 months (maximum: 110 months). Globally, 64.8% of our patients required to step up to biological therapy with a mean time from onset to biologics of 15.3 months (median 9 months). Seventy-two per cent of those who needed biological treatment started Adalimumab (ADA). During the follow-up, 42.2% of the patients with combo therapy could withdraw AZA, being the main reason (76.3%) clinical and endoscopic remission.

Conclusion
Even though EEN is an effective treatment for the induction of the remission in paediatric CD, in the long term we are not able to maintain that remission and an important percentage of patients require to step up to biological therapy. The definition of more strict criteria of remission is necessary in order to establish the most suitable maintenance treatment for each patient.
P630 Complete endoscopic remission is not only associated with higher mucosal concentrations of 5-aminosalicylic acid but also with N-acetyl-5-aminosalicylic acid in patients with ulcerative colitis
Authors: Fukuda T , Naganuma M , Takabayashi K , Hagihara Y , Tanemoto S , Nomura E , Yoshimatsu Y , Sugimoto S , Nanki K , Mizuno S , Mikami Y , Fukuhara K , Suzino T , Mutaguchi M , Inoue N , Ogata H , Iwao Y , Kanai T 
Published: January 2020

Abstract

Background
The mechanisms behind 5-aminosalicylic acid (5-ASA) activity in ulcerative colitis (UC) are known to exert a beneficial effect by acting topically on colonic mucosa. this study investigated whether mucosal 5-ASA and N-acetyl-5-ASA (Ac-5-ASA) concentrations are associated with endoscopic remission.

Methods
This single-centre, prospective cross-sectional study was conducted between March 2018 and February 2019. Patients with UC who were treated with 5-ASA medications for at least 8 weeks prior to sigmoidoscopy were enrolled. All participants underwent sigmoidoscopy without pre-treatment, and biopsies were performed to extract approximately 10 mg of tissue from the sigmoid colon and rectum. Mucosal concentrations of 5-ASA and Ac-5-ASA were measured using liquid chromatography with tandem mass spectrometry. The main endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA according to the level of either the Mayo endoscopic subscore (MES) or the ulcerative colitis Endoscopic Index of Severity (UCEIS).

Results
Mucosal concentrations were analysed in 50 patients. In the sigmoid colon, the median 5-ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥1 (6.4 ng/mg) (p = 0.019). The median 5-ASA concentration in patients with UCEIS ≤1 (16.4 ng/mg) was also significantly higher than in patients with UCEIS ≥2 (4.63 ng/mg) (p = 0.047). Interestingly, the concentration of Ac-5-ASA was higher in patients with an MES of 0 (21.2 ng/mg) than in patients with an MES≥1 (5.81 ng/mg) (p = 0.022). Similarly, the Ac-5-ASA concentration was significantly higher in patients with a UCEIS≤1 (21.1 ng/mg) compared with that in patients with a UCEIS≥2 (7.8 ng/mg) (p = 0.048). Furthermore, we compared the concentrations of 5-ASA in patients receiving the maximum dose of the three different formulations (time-dependent, pH-dependent, or multimatrix system 5-ASA). 5-ASA concentrations in both sigmoid colon and the rectum tended to be lower in patients receiving time-dependent 5-ASA than patients receiving pH-dependent 5-ASA or multimatrix system 5-ASA, but the difference was not significant.

Conclusion
Although Ac-5ASA, a metabolite of 5-ASA is thought to have few pharmacological effect, this study demonstrated that patients with complete endoscopic remission had higher mucosal concentrations of not only 5-ASA but also Ac-5-ASA than patients with mild-to-moderate endoscopic severity. This result may be explained by the fact that Ac-5-ASA remains as a metabolite of 5-ASA after contributing to the suppression of inflammation in patients with endoscopic remission.
P658 A pooled analysis of serum phosphate measurements and transient decreased phosphate levels in 45 interventional trials with ferric carboxymaltose
Authors: Stein J M , Schiefke I , Göhring U M , Fabien V , Rosano G 
Published: January 2020

Abstract

Background
ECCO guidelines acknowledge the limitations of oral iron for iron deficiency anaemia in IBD and recommend first-line IV iron in patients with active disease. Ferric carboxymaltose (FCM) is approved for iron deficiency when oral iron is ineffective/inappropriate. FCM has shown benefit in RCTs, and as with other IV irons, is known to cause a transient decrease in serum phosphate (PO4), which in most cases is asymptomatic. The aim of this pooled analysis was to characterise the frequency, duration, risk factors, and clinical signs of hypophosphataemia (HP) across 45 interventional trials with FCM.

Methods
15,080 subjects were included (FCM n = 8,245; controls n = 6,835). 12,683 had post-baseline serum PO4 measurements (FCM n = 6,879), which were pooled by time-point, clinical characteristics, dose, and iron parameters. Serum PO4 thresholds were: 2.5–&lt;4.5 mg/dl (normal), 2.0–&lt;2.5 mg/dl (mild decrease), 1–&lt;2.0 mg/dl (moderate), and &lt;1 mg/dl (severe). Logistic regression analysis was used to identify predictors of HP. MedDRA terms were interrogated for reported and potential clinical signs of HP.

Results
2,760 FCM subjects (40.1%) with normal PO4 at baseline developed HP (PO4 &lt;2.5 mg/dl) on study. PO4 levels normalised in 1,705 subjects (61.8%); mean time to normalisation (±SD) was 40.7 days (±35.31). PO4 normalisation during follow-up did not occur in 177 subjects (0.06%). Independent risk factors for moderate/severe HP within 12 weeks of treatment included treatment setting (gastroenterology or neurology vs. women’s health), lower baseline ferritin level, maximum single-dose, advanced age, lower weight at baseline (all p &lt; 0.0001), multiple doses vs. single dose (p = 0.0003), and higher cumulative dose (p = 0.0005). ‘Hypophosphataemia’ as a MedDRA term was approximately 10-fold more frequent with FCM than controls (2.2% vs. 0.2% with other IV irons). Potential clinical signs of HP were not more frequent with FCM vs. controls (Table) and were not associated with nadir levels of serum PO4. 4 of 49 FCM subjects (8.2%) who had nadir PO4 below 1 mg/dl had a potential clinical sign of HP, vs. 126/1,569 (8.0%) with 1–&lt;2.0 mg/dl, 113/1,229 (9.2%) with 2.0–&lt;2.5 mg/dl and 411/4,032 (10.2%) with ≥2.5 mg/dl. Among subjects with PO4 &lt;2.5 mg/dl, serious cardiac disorders classified as potentially related to HP occurred in 14 FCM subjects (0.5%), 1 (0.7%) other IV iron, and 2 (4.4%) oral iron.

Conclusion
HP is recognised as a common adverse drug reaction with FCM as with several other IV iron preparations. This analysis shows that the transient decreases in PO4 levels were more frequent in patients receiving multiple and/or large doses of FCM but were not associated with an increased rate of potential signs/symptoms of HP.
P664 The impact of vedolizumab on extra-intestinal manifestations in inflammatory bowel disease patients: A real-life experience of a single-centre cohort
Authors: TRUYENS M , Geldof J , Dewitte G , Glorieus E , Varkas G , Elewaut D , Lobaton Ortega T 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ), a gut-specific anti-integrin, is approved as a treatment for moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Extra-intestinal manifestations (EIMs) are frequently associated with inflammatory bowel disease (IBD). However, the effect of VDZ on EIMs remains unknown. The aim of the current study was to describe the prevalence of EIMs in IBD patients at VDZ initiation, the evolution during continued treatment as well as the occurrence of new EIMs.

Methods
A single-centre study was performed in IBD patients who were started on VDZ between May 2010 and February 2019. Retrospectively, the physician-reported EIMs and intestinal disease activity (clinical and endoscopic) were assessed at baseline, 6 months and 1 year after the start of VDZ.

Results
The cohort consisted of 134 patients, including 77 CD patients, 56 UC patients and 1 patient with unclassified IBD. At VDZ initiation EIMs were assessed in 127 patients and 17.3% had ≥ 1 EIM: 9 hepatic EIMs (2 patients with toxic hepatitis, 2 with autoimmune hepatitis and 5 with PSC), 7 arthropathies (6 patients with axial spondyloarthropathy and 1 with peripheral arthritis), 3 non-further specified axial or peripheral arthralgias and 3 cutaneous EIMs (urticaria, psoriasis and erythema nodosum). Clinical evolution of the EIMs is reported in Table 1, assessment of intestinal disease activity in Table 2. During follow-up, 23 new EIMs were seen, mainly arthralgia, which was often transient. VDZ was stopped in 39/130 (30%) patients due to active intestinal disease in 32 patients, patients’ choice (n = 1) or because of deep disease remission (n = 1). In five patients, VDZ was stopped because of insufficient control of EIM.

Conclusion
A good clinical intestinal response was observed. However, the clinical evolution of EIMs appears unaffected by the use of VDZ in our cohort. Prospective data are needed to confirm these results.
P667 Combined therapy of perianal fistulas with autologous adipose-derived stem cells
Authors: Surowiecka A , Łodyga M , Durlik M , Grażyna R 
Published: January 2020

Abstract

Background
Autologous adipose-derived stem cells (ADSCs) are pluripotent medical stimulatory cells. In damaged tissues, they activate regeneration by secretion of various growth factors, anti-inflammatory cytokines and migration factors. Autologous ADSCs are harvested from subcutaneous fat tissue.

Methods
The aim of our study was to create a protocol of combined surgical and biologic treatment of perianal fistulas followed with transfer of autologous ADSCs into fistulas. It was a prospective study. We selected patients diagnosed with Crohn’s disease with perianal fistulas, confirmed in MRI or transanal US, with no symptoms of abscess formation. In this protocol, we started from fistulas setoning. Afterwards, two courses of biologic agents were conducted. In the next step, autologous ADSCs were harvested from subcutaneous fat tissue and transferred to inactive fistulas. We used Arthrex®system to acquire ADSCs. Further courses with biologic agents followed the ADSCs transfer. To evaluate the outcomes we used Pikarky’s Perianal Crohn’s Disease Activity Index. A good resolution was defined as fistula closure, incomplete healing as partial resolution without complete closure and fistula reactivation as no resolution.

Results
In a preliminary study we collected data of 10 patients. The mean volume of lipoaspirate was 30 ml. The mean amount of ADSCs transferred was 4 ml. The mean operative time was 90 min. The early observation time varied from 1 to 3 months. In all cases, these were bifurcated complex and trans-sphincteric fistulas. There were no cases of no resolution. Early results were promising with almost all cases of good resolution. However, longer observation is required.

Conclusion
Autologous adipose-derived stem cells in combination with surgical setoning and biological agents are a good alternative for patients with perianal manifestation of Crohn’s disease.
P676 Faecal monitoring is useful in monitoring treatment response in anti-TNF-treated patients
Authors: Farkas K , Szántó K J , Kata D , Földesi I , Ferenci T , Rutka M , Pigniczki D , Bor R , Fábián A , Szepes Z , Nagy F , Molnár T 
Published: January 2020

Abstract

Background
Faecal drug concentration is not routinely measured as per therapeutic drug monitoring strategies in inflammatory bowel disease (IBD) patients receiving anti-TNF therapy. However, our previous research work suggested the importance of faecal drug monitoring of anti-TNF agents since active disease may be present in spite of normal serum anti-TNF levels. The aim of the present study was to examine the correlation between faecal calprotectin and faecal infliximab (IFX) concentration and to evaluate the cut-off value of faecal drug concentration in the respect of faecal calprotectin in patients treated with maintenance IFX therapy.

Methods
Consecutive patients with IBD receiving maintenance IFX therapy at 1st Department of Medicine, University of Szeged were enrolled in the present study. Faecal samples were obtained before the subsequent IFX infusion. Faecal calprotectin and IFX concentrations were determined with ELISA. The correlation between faecal calprotectin and faecal IFX concentration was statistically assessed.

Results
Sixty-seven IBD patients were enrolled. Female/male ratio was 49%–51%. Sixty-five point six% of the patients were diagnosed with Crohn’s disease and 34.3% with ulcerative colitis. Mean disease duration was 14.9 years (SD 9.7) at the time of analysis. Mean duration of IFX therapy was 42.3 month (SD 31.6). Twenty-eight point three% of the patients received escalated IFX therapy. Mean faecal calprotectin concentration was 545.7 µg/g (SD 379.4 µg/g). Mean faecal IFX concentration was 1 ng/ml (SD 1.3). Faecal calprotectin and faecal IFX concentration showed significant correlation (r=0.37, p = 0.002). A cut-off value of faecal IFX level of 0.6 ng/ml was determined at faecal calprotectin concentration of 500 µg/g.

Conclusion
According to our results IFX is detectable in the faeces at a calprotectin concentration of 500 µg/g. The cut-off value for faecal IFX concentration proved to be 0.6 ng/ml. Simultaneous determination of faecal anti-TNF and faecal calprotectin concentration is supposed to have a higher benefit in the evaluation of response to IFX therapy.
P685 Healthcare resource use associated with ferric maltol and IV iron treatment for iron deficiency anaemia in patients with inflammatory bowel disease
Authors: Howaldt S , Jacob I , Sampson M , Akriche F 
Published: January 2020

Abstract

Background
Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD). IDA imposes a substantial economic burden on healthcare payers resulting primarily from increased medical costs and increased rates of hospital admission. Most guidelines recommend oral iron as first-line treatment, with IV iron if oral supplementation is ineffective or poorly tolerated. Intolerance to ferrous (Fe2+) oral iron is common in patients with IBD. Ferric maltol (FM), a stable oral complex of ferric (Fe3+) iron and maltol, is designed to reduce exposure to elemental iron and thus limit gastrointestinal damage. This analysis compares the Healthcare resource use (HCRU) associated with oral FM and IV ferric carboxymaltose (FCM) treatment.

Methods
Patients with IBD and IDA (haemoglobin [Hb] ≥8.0 g/dl and ≤11.0 g/dl for women or ≥8.0 g/dl and ≤12.0 g/dl for men, and ferritin &lt;30 ng/ml or ferritin &lt;100 ng/ml with transferrin saturation &lt;20%) were randomised to FM (30 mg b.i.d) or IV FCM (as per local SmPC) in an open-label, Phase 3b non-inferiority study. The primary endpoint was Hb responder rate (proportion of patients achieving a ≥2 g/dl increase or normalisation of Hb at week 12); the margin for non-inferiority was 20%. HCRU was assessed based on the total costs of iron therapy (including drug costs and administration), and the number of hospital/outpatient visits during the initial 12-week study period. Costs of IV FCM and FM were applied to a German setting.

Results
250 patients were randomised: 125 to FM and 125 to IV FCM. The primary endpoint was not met. Mean (standard deviation; SD) total treatment costs per patient in the FM and IV FCM arms were €302.27 (€80.68) and €489.37 (€147.19) respectively. Eighty-seven per cent of FM patients were still receiving treatment at week 12, and 45% and 36% of IV FCM patients required a repeat course of IV iron at weeks 4 and 12, respectively. The mean (SD) number of hospital/outpatient visits during the study period for patients receiving IV FCM was 2.30 (0.88) and the total dose of IV FCM received was 1621 mg (491 mg).

Conclusion
Total per patient drug costs were approximately 1.6 times higher for treatment with IV FCM than FM. The total cost of IV FCM is not only influenced by the higher drug cost, but additional costs associated with IV administration which was required to be carried out in a hospital or outpatient setting. FM has no additional costs or resource use associated with administration and is, therefore, less of a burden on local healthcare systems. FM is associated with substantially lower HCRU than IV FCM, and may provide a cost-effective oral alternative to IV iron in patients with IBD.