bluuebunny/crossref_metadata_2025_split huggingface dataset:
P328 Faecal microbiota transplantation as treatment for recurrent Clostridiodes difficile infection in patients with inflammatory bowel disease: Experiences of the Netherlands donor faeces bank
Authors: Van Lingen E , van der Meulen-de Jong A E , Vendrik K E W , Kuijper E J , Terveer E M , Keller J J 
Published: January 2020

Abstract

Background
In recent years Faecal Microbiota Transplantation (FMT) is effectively implemented as an approved treatment approach of refractory Clostridiodes difficile infection (rCDI). In patients with inflammatory bowel disease (IBD) the prevalence of co-infection with CDI is higher than in the general population due to the use of immunosuppressive medication and dysbiosis of the bacteria in the colon. Just a small percentage of IBD patients do have an active CDI infection, not to be confused with carriership. Here we report the treatment course and efficacy of FMT provided by the Netherlands Donor Faeces Bank (NDFB) for IBD patients with rCDI.

Methods
The NDFB was founded to facilitate FMT by providing ready to use donor faeces suspensions for treatment of patients with rCDI in hospitals throughout The Netherlands. A request for FMT is evaluated by the working group (specialists in the fields of Medical Microbiology, Gastroenterology, and Infectious Diseases) to assess the indication of FMT and to formulate a treatment advice for each individual patient taking the comorbidity into account. Prior to FMT, all patients were pre-treated with vancomycin 250 mg for at least 4 days and bowel lavage. In patients with ulcerative colitis as comorbidity, prednisone was added when there was an IBD flare simultaneous. The results of FMT were monitored by prospective collection of outcome data by the NDFB.

Results
Since the start of NDFB in March 2016 until August 2019, 186 FMT requests to treat 176 (r)CDI patients were reviewed within the NDFB working group including 26 patients with rCDI and IBD. In total, 129 patients (of which 14 suffered from IBD) were treated with 143 FMTs for CDI with a cure rate of 89.9% after a single FMT (116/129). FMT was deemed not suitable in 12 of 26 patients with IBD because patients had C. Difficile carriership instead of an active CDI infection. Fourteen IBD patients were treated with FMT (9 ulcerative colitis, 2 Crohn’s disease and 2 indeterminate colitis). 3/14 patients suffered from rCDI with an active episode of IBD. Of the 14 IBD patients treated with FMT, only one patient developed a relapse of a CDI infection within 2-months (total cure rate 92%). This cure rate does not differ from CDI patients without IBD.

Conclusion
In IBD patients with rCDI, FMT is equally effective compared with other patients with rCDI. In case of concurrent activity of IBD, pre-treatment with prednisolone in combination with vancomycin appears to be effective.
P331 Productivity loss in patients with inflammatory bowel disease receiving treatment for iron deficiency anaemia: A comparison of ferric maltol and IV iron
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) and can significantly impair health-related quality of life. IDA imposes a substantial economic burden on healthcare payers resulting primarily from increased medical costs and increased rates of hospital admission. IV iron is currently the main treatment for patients intolerant or unsuitable for standard oral iron. 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 productivity loss 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 receive 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%. Productivity loss was calculated based on the number of days lost due to iron therapy during the initial 12-week study period. The costs associated with lost productivity were calculated using the human capital approach and based on the average gross income from Germany.

Results
250 patients were randomised: 125 to FM and 125 to IV FCM. The primary non-inferiority endpoint was not met. IV FCM treatment resulted in a loss of patient time because IV administration was limited to a hospital or outpatient setting: 50% of patients treated with IV FCM lost at least one full day due to treatment, with 1 in 15 losing 4–6 days (Table 1). Productivity loss was quantified, with IV FCM treatment associated with losses between €0.00 and €107.21 in 50% of patients, €129.17 and €387.51 in 43% of patients and €516.68 and €775.02 in 7% of patients. FM was administered orally by the patient and did not require any in-hospital treatment, there was no treatment linked productivity loss.

Conclusion
IV FCM treatment resulted in productivity loss and disruption to patients’ work and family life due to the need for in-hospital/outpatient IV administration. FM treatment had no associated productivity loss as it was administered orally by the patient. FM has none of the indirect costs associated with IV FCM administration and may provide an oral alternative to IV iron in patients with IBD.
P333 Biologic longevity: Withdrawal of drugs due to remission is rare in clinical practice
Authors: Sharma E , Cunningham G , Dawson P , D’Errico F , Honap S , Lim S , Luber R , Meade S , Pavlidis P , Reynolds R , Irving P 
Published: January 2020

Abstract

Background
Biological medicines are well established in the treatment of inflammatory bowel disease (IBD). The aim of this study was to review the natural history of biologic use in a large cohort of patients from a tertiary centre.

Methods
We performed a retrospective review of prospectively collected records of patients with Ulcerative colitis (UC) and Crohn’s disease (CD) from a single centre. All patients who received ustekinumab, golimumab and vedolizumab between April 2014 and May 2019 were included as were a similar sized cohort of patients who received adalimumab and infliximab. Demographic data, use of concomitant immunomodulation, length of time on drug and reason for stopping treatment were recorded.

Results
The patient cohort is described in Table 1. Median (range) follow-up was 32 (3–61) months. Infliximab and golimumab were used first line in 92 (94%) patients and 83 (87%) patients, respectively. Ustekinumab and vedolizumab were used later on in treatment with 38 patients receiving ustekinumab third line (47%) and vedolizumab being used second line in 52 patients (44%) and third line in 43 (37%) patients. Table 2 describes the reasons for biologic cessation. Other reasons for discontinuation included adverse drug reaction, pregnancy and patient choice. Concomitant immunomodulation at initiation of biologic was seen in 228 (79%) patients on TNF antagonists, 58 (50%) patients on vedolizumab and 44 (54%) patients on ustekinumab.

Conclusion
In CD, adalimumab and infliximab display a longer drug survival compared with ustekinumab and vedolizumab possibly due to treatment positioning. In UC, vedolizumab is associated with more treatment persistence than golimumab. Across all biologics, documented cessation due to remission was low, especially in those biologics that are used second or third line.
P342 Diagnostic accuracy of rectal bleeding and stool frequency in predicting mucosal healing in patients with ulcerative colitis in the tofacitinib OCTAVE Phase 3 induction studies
Authors: Colombel J F , Bushmakin A G , Cappelleri J C , Kulisek N , Santana G O , Lawendy N , Ponce de Leon D , Lakatos P L 
Published: January 2020

Abstract

Background
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In patients with UC, associations between endoscopic findings and patient-reported outcomes, such as stool frequency (SF) and rectal bleeding (RB), are not well described. Here, we evaluated the diagnostic accuracy of Mayo SF and RB subscores to predict mucosal healing (MH) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951).

Methods
This post hoc analysis used data from OCTAVE Induction 1 and 2, two identical, randomised, placebo-controlled, 8-week, Phase 3 studies of tofacitinib for the treatment of patients with moderately to severely active UC.1 SF (Mayo subscore 0–3), RB (Mayo subscore 0–3) and endoscopic findings (Mayo endoscopic subscore [ES] 0–3) were assessed at baseline and at Week 8. MH and endoscopic normalisation were defined as an ES of 0 or 1, or an ES of 0, respectively. Based on two-by-two contingency tables, diagnostic test characteristics for SF and RB were evaluated: positive and negative predictive values, sensitivity and specificity. Kappa statistics (chance-corrected measure of agreement) and Pearson correlations (a measure of association) were also calculated. All available data at Week 8 were used.

Results
A total of 614 and 547 patients received treatment (tofacitinib 15 or 10 mg BID, or placebo) in OCTAVE Induction 1 and 2, respectively. Two-by-two contingency table analyses showed that dichotomised SF (0 vs. ≥1) and RB (0 vs. ≥1) were each or both not good predictors of MH (ES of 0 or 1 vs. ≥2) or endoscopic normalisation (ES 0 vs. ≥1), as ≥1 of the four diagnostic test characteristics was &lt;50% (Table). In OCTAVE Induction 1 and 2, weighted kappa statistics for SF (original metric 0–3) and RB (0–3) vs. ES (0–3) indicated moderate agreement for SF (0.46 and 0.42, respectively), slight agreement for RB (0.19 and 0.15, respectively) and fair agreement for SF and RB (0.40 and 0.34, respectively). Correlations were 0.54 and 0.49 for SF, 0.46 and 0.37 for RB and 0.57 and 0.51 for SF and RB (OCTAVE Induction 1 and 2, respectively), suggesting a modest-to-moderate association.

Conclusion
In patients with UC treated with tofacitinib or placebo in OCTAVE Induction 1 and 2, SF and RB subscores had slight-to-moderate agreement with ES, but were not predictive of MH or endoscopic normalisation. The presence of blood at Week 8 strongly indicated that patients had endoscopic activity, but the absence of blood was associated with MH in &lt;50% of patients. Further analysis is needed to fully understand the relationship between SF, RB and MH.

Reference
P359 Platelet-rich stroma injection (PRS) as a novel surgical treatment of refractory perianal fistulas in Crohn’s disease: A pilot study
Authors: Arkenbosch J , van Ruler O , Dwarkasing R S , Schouten W R , de Vries A C , de Graaf E J R , van der Woude C J 
Published: January 2020

Abstract

Background
Perianal fistulizing Crohn’s disease (FCD) comes with significant morbidity and severe reduced quality of life. Treatment of FCD is challenging and includes immunosuppressive drugs, antibiotics and surgery. All therapies are associated with high recurrence rates. Platelet-rich stroma (PRS) is a combination of platelet-rich plasma (PRP) and stromal vascular fraction (SVF). Autologous PRS includes stromal cells in their matrix with stimulating factors, plays an essential role in wound repair and defence mechanisms against infection and is easy to obtain and inject. Because of its operating mechanism, PRS could be of additional value in patients with refractory FCD. This study aims to assess the feasibility, safety and efficacy of local injection of PRS in patients with refractory FCD.

Methods
After informed consent, 10 patients (age ≥16 years) with refractory FCD were included between March 2018 and July 2019. Exclusion criteria were rectovaginal fistulas, persistent proctitis and pelvic abscesses. All patients underwent surgery with harvesting of subcutaneous fat and venous blood sampling to obtain 6 ml of PRS (1 ml of SVF resp. 5 ml of PRP), excision of the external opening(s), fistula curettage, and injection of PRS in the fistula wall and closure of the internal opening. A pre- and postoperative MRI was performed. Endpoints were clinical outcome, both closure and absence of discharge at physical examination, patient-reported outcome (no effect/moderate effect/major effect), as well as radiological outcome (van Assche score). From 3 months postoperative, re-injection of PRS was considered in patients with unfavourable clinical and/or radiological outcome.

Results
All patients (4:6 female:male; median age 33 (IQR 22.9–38.7) had infralevatoric fistulas with a median van Assche score of 17 [range 14–20] without rectal involvement and abscesses. Median follow-up was 6 months [4–12]. The median duration of FCD was 4 years (IQR 2–5). The median number of drugs given were 4 [1–7] and number of operations 3 [2–3], including stoma formation in 2 patients. Crohn’s disease activity outside the anorectum was present in all patients. 7 patients underwent 1 PRS injection and 3 patients 2 injections. There were no complications of the PRS injection. Fistula closure was present in 5 patients and open in 5 patients, of which 2 patients had no signs of discharge. One patient underwent restoration of bowel continuity. Of 7 postoperative MRIs available to date, median decrease of van Assche score was 4 (17 vs. 13)[0–15]. Patient-reported outcome was major effect in 4, moderate effect in 3, and no effect in 3 patients.

Conclusion
Autologous PRS appears to be feasible, safe and promising in the treatment of refractory perianal fistulizing Crohn’s disease.
P369 Mycobacterium tuberculosis infection among patients with inflammatory bowel disease under biologics: experience of Croatian Tertiary Centre
Authors: Ogresta D , Bišćanin A , Tomašić V , Dorosulić Z , Kralj D , Forgač J , Ćaćić P , Lerotić I , Hrabar D 
Published: January 2020

Abstract

Background
Mycobacterium tuberculosis infection (TB) causes a huge number of deaths in the world. A majority (95%) of infections remain asymptomatic, defined as latent tuberculosis (LTB). The estimated incidence rate of TB in Croatia is 10.6 cases per 100 000 inhabitants. Patients with inflammatory bowel diseases (IBD) usually require immunosuppressive therapies which puts them at higher risk for infection. LTB diagnosis and prophylactic treatment are recommended for all patients starting biologics.

Methods
A single-centre retrospective study in the continental part of Croatia included all IBD patients who started treatment with biologics and have presented with TB or LTB from January 2016 till September 2019. The aim was to evaluate the prevalence of LTB among patients with IBD before starting biologic therapy, and TB reactivation during treatment with biologics. All patients underwent Interferon Gamma Release Assay (IGRA) and X-ray. Active infection was excluded or diagnosed using clinical history, bronchoscopy, CT scan and sputum stain for Mycobacteria.

Results
Study population included 74 patients treated with biologics: 51% female, 73% Crohn’s disease (CD); 37% starting adalimumab, 29% infliximab, 19% ustekinumab and 15% vedolizumab. Prevalence of LTB was 8.1% (6 patients), and all patients underwent isoniazid prophylaxis for 9 months except one patient treated with conventional immunomodulatory therapy which failed prophylactic therapy with both isoniazid and rifampin (liver injury). Among patients with adequate chemoprophylaxis, two patients later on started with anti-TNF therapy (adalimumab), two patients with vedolizumab and one with ustekinumab. One patient with CD and negative LTB screening developed pulmonary TB during induction with infliximab (1 month after initiation); after successful treatment with conventional fourfold therapy, the patient was switched to vedolizumab. During the observational period (median 16 months), all IBD patients with LTB as well with cured TB were in clinical and biochemical remission, without signs of TB (re)activation.

Conclusion
Our study has demonstrated that prevalence of LTB among our IBD patients starting biologics was significant (8.1%). Treatment with vedolizumab, ustekinumab and anti-TNF (adalimumab) after isoniazid chemoprophylaxis appears to be safe during the observational period, without signs of TB reactivation.
P381 Use of ustekinumab in Crohn’s disease: Singapore largest single-centre experience
Authors: Shim H H , Kong S C , Ong W C , Lim T G , Chan P W 
Published: January 2020

Abstract

Background
Ustekinumab is the latest therapeutic option for Crohn’s disease (CD). Efficacy and safety outcomes of its use in the Asia CD population, however, have not been reported.

Methods
Patients with CD who received minimum 14 weeks of UST were included. The primary outcome was the percentage of patients who achieved remission by global physician assessment, GPA [defined by Steroid Free Remission (Harvey Bradshaw Index ≤4 and absence of systemic corticosteroid), stool calprotectin &lt;250 μg/g and CR p &lt; 5mg/l] at baseline, weeks 14, 24 and 54. Secondary outcomes included steroid-free remission, normalisation of CRP (&lt;5mg/l), mucosal healing (absence of mucosal ulceration), transmural healing (absence of disease activity on CT/MR enterography); and adverse events including infection, infusion reaction, malignancy and surgery.

Results
Twenty-two patients were included in this study (Table 1). 22.7%, 50% and 55.6% of patients achieved remission by GPA at weeks 14, 24 and 54 respectively (Table 2). Two (2/5.40%) patients achieved mucosal healing with the median time to scope of 12 (IQR 4.5–15) months. Three (3/7, 42.9%) patients achieved transmural healing with the median time to scan of 8 (IQR 5–11) months. Reported on-treatment infection included pharyngitis, adenovirus, norovirus diarrhoea, dental abscess, shingles and cutaneous Mycobacterium abscessus. Four had surgery during the follow-up. No cases of an infusion reaction or malignancy were reported.

Conclusion
Efficacy and safety profile of ustekinumab in local patients with CD is comparable to their western counterpart in this first real-world Asia cohort.
P382 Application of enhanced recovery after surgery in single-port laparoscopic partial small intestine resection in the treatment of Crohn’s disease
Authors: LI Y , Zhou Z , Yao D , Zheng L , Duan Y , Liu B , Huang Y 
Published: January 2020

Abstract

Background
Single-incision laparoscopic surgery (SILS) with enhanced recovery after surgery (ERAS) can reduce operation trauma and accelerate postoperative rehabilitation. This study aims to investigate the safety and feasibility of SILS with ERAS in the treatment of Crohn’s disease.

Methods
Thirty patients with Crohn’s disease were randomly assigned to receive traditional laparoscopic surgery plus ERAS (n = 20) and SILS plus ERAS (n = 18)，respectively. Comparisons and analysis were made between the two groups in the perioperative conditions.

Results
There were significant differences in the mean operation time between the two groups (p &lt; 0.01)，There were no significant differences in the intra-operative blood loss, postoperative complications rates, the time to first flatus and treatment cost (p &gt; 0.05). There were significant differences in the postoperative hospital stay between the two groups (p &lt; 0.05). WBC, CRP and PCT in SILS plus ERAS group were lower than those in the control group at the first days and the third days after operation, the differences were statistically significant (p &lt; 0.05).

Conclusion
SILS plus ERAS can shorten postoperative hospital stay and facilitate bowel function recovery in the treatment of Crohn’s disease. It is worthwhile to mention the nice cosmetic benefits of SILS, the perioperative SILS plus ERAS program is safe and effective and should be popularised in Crohn’s disease.
P384 Lower infliximab trough levels are associated with higher bowel wall thickness in Crohn’s disease
Authors: Frias Gomes C , Morão B , Neto Nascimento C , Gouveia C , Palmela C , Strecht J , Torres J 
Published: January 2020

Abstract

Background
Therapeutic drug monitoring (TDM) is currently used to optimise anti-TNFα therapy in Crohn’s disease, as higher infliximab trough levels (ITL) are associated with better rates of clinical remission and mucosal healing. Transmural healing is emerging as a potential target in Crohn′s disease, but whether there is any relation with ITL remains unclear. Here, we investigated the relation between ITL with bowel wall thickness (BWT) in patients with CD in maintenance therapy with IFX.

Methods
A retrospective cohort study of CD patients treated with IFX in mono or combination therapy. Patients were included if they had an available ITL during maintenance therapy and available entero-magnetic resonance or computerised tomography performed ±4 months. Transmural inflammation was defined as BWT ≥ 4 mm. Median BWT was measured in the most affected segment. An ROC curve was plotted to determine the best cut-off point of ITL to predict transmural inflammation. Mann–Whitney U-test, logistic regression and Spearman correlation were performed to assess the ITL relation with BWT.

Results
Twenty-nine patients were included (males 55.2%; mean age 39.6 ± 18 years; combo therapy 48.2%). According to the Montreal Classification, most patients were A2 (75.2%), with ileal (L1: 34.5%) or ileocolic disease (L3: 51.7%), and behaviour was: B1 41.4%, B2 24.1%, and B3 34.5%, with concomitant perianal disease in 37.9%. 82.2% were in clinical remission. The median IFX TL was 3.2 μg/ml (IQR 1.15–5.15) and median bowel wall thickness was 7 mm (IQR 4–9). 75.9% of patients had BWT &gt; 4 mm. A BWT &gt; 4 mm was associated with lower clinical remission rates (75% vs. 100%, p = 0.27) and higher C-reactive protein (0.31 vs. 0.14, p = 0.09), albeit not significantly. The area under the curve of ITL for bowel wall thickness was 0.70 (best cut-off value 1.8). Having ITL &lt; 1.8 μg/ml was associated with higher median BWT (8.7 vs. 5.9 mm, p = 0.02) and was a predictive factor for transmural inflammation (OR 1.57, 95% CI [1.08–2.30], p = 0.02). BWT showed a fair correlation with ITL (r = −0.43, p = 0.02).

Conclusion
In our cohort of CD patients treated with infliximab (mono or combo therapy), lower infliximab trough levels were associated with higher bowel wall thickness, reflecting worse transmural inflammation. Proactive TDM could offer a possibility to improve BWT and reduce transmural inflammation.