bluuebunny/crossref_metadata_2025_split huggingface dataset:
P429 Mesalazine has no place in the treatment of Crohn’s disease. Really?
Authors: Mantzaris MD- PhD- AGAF- FEBG- MACG G , Archavlis E , Christidou A , Viazis N , Karampekos G 
Published: January 2022

Abstract

Background
According to international guidelines mesalazine may have no place in the treatment of Crohn’s disease (CD). However, real-world studies have shown a defined, 5-ASA-dependent group of patients with CD whereas a large proportion of CD patients in the community is still being treated with mesalazine. We aimed at studying the clinical, biomarker and endoscopic characteristics and the course of disease in a selective group of patients on maintenance treatment with mesalazine since the diagnosis of CD.

Methods
This is a prospective, single-center study. Patients followed in IBD clinic were included in a, 15-yearlong observational study starting in the, 1st year after confirmed diagnosis of CD provided that they were in deep remission defined as clinical remission (Harvey-Bradshaw Index, HBI, &lt;5, with normal biomarkers [C-reacting protein (CRP) &lt;0.6 mg/dl and/or Faecal Calprotectin (FC) &lt;150 μg/g faecal tissue] and complete or near complete mucosal healing (&lt;10 or &lt;5 focal micro-aphthous or aphthous ulcers, respectively) assessed by ileocolonoscopy and/or capsule endoscopy. Patients with normal HBI but persistent elevations of CRP and/or FC at baseline were excluded. Patients were followed prospectively every, 3–6 months with HBI score, FBC, LFTs, CRP and/or FC; ileocolonoscopy or CE were performed every, 2–3 years unless they had a flare of CD. Patients who during follow up developed a flare (HBI&gt;4) associated with persistently abnormal CRP and FC and deterioration of the endoscopic findings vs baseline were considered as treatment failures.

Results
Patient demographic, clinical, biomarker and endoscopic data at baseline and during the course of CD is shown in Table, 1. Ileocolonoscopy findings remained persistently unchanged in all but, 2 patients who developed a flare and needed escalation of treatment after, 2 and, 3 years, respectively. CE was performed at two different times during follow up in, 8 patients with L1 phenotype and did not show any change in the number of detected lesions. Overall, 35 of, 55 patients had a voluntary drug holiday for, 4–6 months resulting in a rise of HBI to, 6–8 and mild elevations of FC (200–300 μg/g) but not of CRP; however, clinical symptoms were relieved and HBI and FC returned to normal following re-initiation of mesalazine indicating, 5-ASA dependence. None of the patients reported disease complications or treatment-related adverse events

Conclusion
There is a distinct group of non-smoking patients with mild CD (on clinical, biomarker, and endoscopy grounds) at diagnosis who are in deep remission at the end of the, 1st year following treatment with mesalazine. These patients maintain a, 5-ASA-dependent deep remission as long as they are compliant with treatment.
P434 The PROPER study: interim analysis of a Pan-European real-world study of SB5 adalimumab biosimilar after transition from reference adalimumab in patients with Crohn’s disease
Authors: Dignass A U , Gisbert J P , Bossa F , Freudensprung U , Addison J 
Published: January 2022

Abstract

Background
SB5, a biosimilar to reference adalimumab (ADL), received EU marketing authorisation in August, 2017, based on pre-clinical and clinical phase I and III studies that demonstrated bioequivalence and comparable efficacy, safety and immunogenicity profiles to ADL. The real-world study ‘PROPER’ is designed to provide insights into outcomes of the transition from reference to SB5 outside the controlled, randomised, clinical trial setting. Under an umbrella design, 1000 patients with immune-mediated inflammatory disease have been enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK.

Methods
Eligible patients had been transitioned to SB5 as part of routine treatment following a minimum of, 16 weeks’ treatment with ADL. Data were captured from patient charts retrospectively for, 24 weeks prior to and prospectively and/or retrospectively for, 48 weeks after SB5 initiation. This interim analysis of the Crohn’s disease cohort reports outcome measures including clinical characteristics, disease activity, persistence on SB5, clinical management and safety for patients enrolled at, 32 specialist sites and followed up to the data extract date of October, 5th, 2021.

Results
Of the, 462 patients included in this interim analysis, the majority were enrolled in Germany (n=127), Spain (n=118) and Italy (n=79); Belgium, Ireland and UK enrolled, 56, 46 and, 36 patients, respectively. At time of data extract, 416 patients had completed, 48 weeks of follow-up and, 15 had withdrawn from the study.
The most common reasons driving transition were physician decision, or a mandate from the health authority or payer. At baseline, the majority of patients were in remission or had mild disease as determined by Harvey Bradshaw Index (HBI), and were in remission or stable according to physician opinion. Most patients transitioned to the same SB5 regimen as they had received for ADL (Table 1).
Twenty-four patients reported, 27 serious adverse events (SAE), of which, 4 (anal fistula [n=1], perianal abscesses [n=2] and subileus [n=1]) were considered by the study physician to be related to SB5 administration.

Conclusion
No meaningful change in HBI or SB5 dosing regimen was observed from baseline to Week, 48 after transition from ADL. The number of patients experiencing a treatment-related SAE was low, and no new safety concerns were detected. Thus, transition from ADL to SB5 was generally safe and effective in patients with Crohn’s disease over, 48 weeks of follow-up.
Acknowledgements:
This study was funded by Biogen International GmbH. Statistical services were provided by FGK Clinical Research GmbH, Munich, Germany. Data management services were provided by Worldwide Clinical trial, Research Triangle Park, NC, USA.
P435 High rate of vitamin deficiencies in patients after total proctocolectomy and pouch surgery- results from a prospective cohort
Authors: Elial-Fatal S , Pfeffer-Gik T , Raykhel B , Friedenberg A , Margolis L , Barkan R , Ollech J , Yanai H , Wasserberg N , White I , Dotan I , Godny L 
Published: January 2022

Abstract

Background
Patients with ulcerative colitis (UC) undergoing total proctocolectomy with ileal pouch anal anastomosis (pouch surgery) may be prone to develop nutritional deficiencies. Here we aimed to evaluate the rates of vitamin deficiencies and their risk factors in these patients.

Methods
Patients after pouch surgery were consecutively enrolled in a tertiary referral center. Pouch behavior determined clinically (normal pouch; recurrent acute pouchitis; chronic pouchitis; Crohn’s like disease of the pouch), disease activity, inflammatory markers and serum vitamin D, B12 and folic acid levels were repeatedly assessed. Body mass index (BMI) and the use of dietary supplements were recorded at each visit.

Results
A total of, 136 patients (mean age-, 47.5±16 years, mean BMI-, 24.9±5 Kg/m2, female gender, 58%) underwent, 721 study visits. Average visits/patients:, 5 (range, 1–15); between-visit interval:, 5±4 months. Normal pouch:, 41%, recurrent acute pouchitis, 24%, chronic pouchitis/ Crohn’s like disease of the pouch:, 35%. Vitamin D deficiency (&lt;25 nmol/L) and insufficiency (25–75 nmol/L) were detected in, 6.5% and, 82% of patients, respectively. Vitamin B12 deficiency (&lt;221 pmol/L) was detected in, 29%, and folic acid deficiency (&lt;7 nmol/L) in, 9.5% of patients. After controlling for disease activity and inflammatory markers, vitamin D deficiency was positively associated with pouch age (i.e interval from the ileostomy closure, OR=, 1.47, 95%CI, 1.1–1.9, p=, 0.007). Vitamin B12 deficiency was positively associated with BMI (OR=1.07, 95%CI, 1.001–1.14, p=0.045), and folic acid deficiency was inversely associated with patient’s age (OR=, 0.95, 95%CI, 0.9–0.99, p=0.017). Of patients with vitamin D, B12 and folic acid insufficiencies or deficiencies, only, 60/121 (49.6%), 17/40 (42%), and, 4/13 (30%), respectively, reported the use of appropriate dietary supplements throughout the long-term follow-up.

Conclusion
In a longitudinal follow up of patients with UC after pouch surgery, we detected significant vitamin D, B12 and folic acid deficiencies and identified specific risk factors. Insufficient active correction with dietary supplements was noticed. Screening and improved correction of nutritional deficiencies should be a part of the routine pro-active multidisciplinary care of patients after pouch surgery.
P437 Reoperations and long-term survival of Kock’s continent ileostomy in Inflammatory bowel disease patients: a population based national cohort study from Sweden
Authors: Risto A , Andersson R E , Landerholm K , Bengtsson J , Block M , Myrelid P 
Published: January 2022

Abstract

Background
Kock’s continent ileostomy is an option after proctocolectomy for patients not suitable for ileal pouch anal anastomosis or ileorectal anastomosis. Ulcerative colitis is the most common indication for continent ileostomy. The aim of this study was to evaluate the long-term outcome of continent ileostomy.

Methods
All patients with inflammatory bowel disease and a continent ileostomy were identified from the Swedish National Patient Register. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy was obtained. Patients with inconsistent diagnostic coding were classified as IBD-unclassified.

Results
Some, 727 patients were identified, 428 (59%) with Ulcerative colitis, 45 (6%) with Crohn’s disease and, 254 (35%) with IBD-unclassified. After a median follow-up time of, 27 (IQR, 21–31) years, 191 (26%) patients had never had revisional surgery. Some, 1,484 reoperations were performed on, 536 (74%) patients, the median number of reoperations was, 1 (IQR, 0–3) per patient. The continent ileostomy was excised in, 77 (11%) patients. Reoperation within the first year after reconstruction was associated with higher rate of revisions (IRR, 2.90 p&lt;0.001) and shorter time to excision (HR, 2.38 p&lt;0.001). Constructing the continent ileostomy after year, 2000 was associated with increased revision and excision rates (IRR, 2.7 p&lt;0.001 and HR, 2.74 p=0.013). IBD-unclassified was associated with increased revisions (IRR, 1.3 p&lt;0.001) and the proportion of IBD-unclassified patients almost doubled from the, 1980s (32%) to after, 2000 (50%).

Conclusion
Continent ileostomy is associated with substantial need for revisional surgery, but most patients get to keep their reconstruction for a long time.
P441 Adalimumab versus ustekinumab as first-line biological in a real-life cohort of moderate-to-severe Crohn’s disease
Authors: Moens A , Verstockt B , Alsoud D , Sabino J , Ferrante M , Vermeire S 
Published: January 2022

Abstract

Background
As therapeutic options in Crohn’s disease (CD) are growing, new challenges including choice of first line therapy arise. Both adalimumab (ADM) and ustekinumab (UST) are effective at inducing and maintaining endoscopic remission in moderate-to-severe CD. Recently, the SEAVUE trial (Sands et al. DDW, 2021) did not show a difference in (steroid-free) clinical remission nor endoscopic remission at week, 52 in biological-naive patients with moderate-to-severe CD. Our aim was to explore if these results withstand in a real world setting of biological-naive CD patients starting their first biological.

Methods
This retrospective cohort study included adult, biological-naive CD patients starting ADM or UST between, 2017–2020 in our tertiary referral centre. Patients were eligible for biological therapy as per reimbursement criteria and all had endoscopy-proven moderate-to-severe disease (at least one ulcer of any size) prior to start of therapy. ADM could be dose optimized. Clinical remission was defined as a Harvey-Bradshaw Index (HBI) &lt;, 5. Endoscopic remission (SES-CD&lt;3) and improvement (≥50% reduction in SES-CD) were assessed at W26-52. Treatment persistence was defined as still being on ADM or UST by the end of follow-up. Missing values were imputed as nonresponses for binary outcomes.

Results
A total of, 70 consecutive biological-naive CD patients were included (38 ADM, 32 UST) and prospectively followed for, 60 (33–104) weeks. Baseline characteristics were similar between both treatment groups (Table, 1). Median (IQR) time to endoscopy was comparable between both groups [ADM, 26 (23–33) vs. UST, 25 (24–45) weeks; p=0.38]. Clinical remission rates, only in patients with active clinical disease at baseline, at week, 26 (ADM:, 72% vs. UST:, 48%, p=0.09) and, 52 (ADM:, 62% vs. UST:, 35%, p=0.09) were numerically but not statistically different between groups. However, ADM was superior to UST in achieving endoscopic remission (61% vs., 31%, p=0.02) and improvement (74% vs., 47%, p=0.03) at week, 26–52. Fifteen (39%) patients in the ADM and, 6 (19%) in the UST group were on steroids at baseline. Numerical differences in steroid-free endoscopic remission (55% vs., 31%, p=0.06) and improvement (68% vs., 47%, p=0.09) rates were seen between ADM and UST at week, 26–52. Rates of treatment persistence were not significantly different between both treatment groups (p=0.31; Figure, 1). The number of adverse events was similar in both groups after one year of therapy (p=0.98).

Conclusion
In a real-world cohort of biological-naive CD patients, ADM seems superior to UST in achieving endoscopic remission and improvement, but no difference was seen in clinical remission at W26-52.
P452 Tofacitinib Effectiveness and Safety as Therapy for Ulcerative Colitis
Authors: McNally M , Keating E , Gray E , McCormick E , Carroll A , Palmer C , Kennedy U , McKiernan S , MacCarthy F , Dunne C , Hartery K , Egan L , Slattery E , Ryan B , McNamara D , O’Connor A , Breslin N , O’Donnell S , Cullen G , Mulcahy H , Sheridan J , Doherty G , Kevans D 
Published: January 2022

Abstract

Background
Tofacitinib is an oral small molecule directed against the JAK/STAT pathway. It is the first JAK inhibitor approved for the treatment of ulcerative colitis (UC) and is licenced for use in moderate to severely active disease. This study aims to evaluate tofacitinib effectiveness and safety in real-world clinical practice for moderate-to-severely active UC.

Methods
Consecutive patients receiving Tofacitinib for UC in four Irish tertiary referral centres were identified. Baseline clinical data and information on therapy outcomes were collected by retrospective review of electronic patient records. Patients included in the study cohort were older than 18 years of age, had a confirmed diagnosis of UC, had received at least one induction dose of tofacitinib, and had available clinical follow-up. The primary study endpoint was 6-month corticosteroid-free remission rate. Secondary endpoints included 3-month clinical response, inflammatory biomarkers responses to tofacitinib therapy, rates of tofacitinib discontinuation, and side effects. Continuous variables are presented as median [range]. P values &lt; 0.05 were considered significant in all analyses.

Results
Fifty-three UC patients were included; age 40.4 [33.3 – 53.9] years, 66% male, disease duration 5.7 [2.6–10.9] years; follow-up 8.7 [6.4–14.1] months. 43%, 40% and 17% of patients had extensive, left-sided disease and proctitis respectively. At baseline, clinical Mayo subscore was 7 [5–8], CRP 4.0 [1.0–16.7] mg/L and faecal calprotectin 914 [444.0–1000] mcg/g. The 3-month clinical response and 6-month corticosteroid-free remission rates were 69% and 43%, respectively. Following tofacitinib therapy, compared with baseline values, a significant reduction in 3-month clinical Mayo score, 3-month CRP, and post-induction faecal calprotectin was observed, p &lt;0.03 for all comparisons. 36% of patients (n=19) discontinued tofacitinib during study follow-up (time to Tofacitinib discontinuation 1.9 [0.5–18.9] months). Side effects occurred in 26% percent of patients with the majority minor and self-limiting. No cardiovascular or venous thromboembolic events were observed and no hospitalisations occurred due to therapy-related side effects

Conclusion
These data are in concordance with prior studies of tofacitinib effectiveness and safety in real world practice. They demonstrate that, in a cohort of UC patients with significant prior therapy exposure, tofacitinib is an effective therapy with an acceptable safety profile.
P462 Upfront infliximab dose intensification for secondary loss of response in IBD: similar efficacy to dose interval shortening with the added advantage of early clinical and pharmacokinetic predictors of response
Authors: Srinivasan A , De Cruz P , Sam M , Toong C , van Langenberg D 
Published: January 2022

Abstract

Background
The efficacy and pharmacokinetic profile of upfront dose intensification strategies such as re-induction (RI) have not been well described, nor directly compared with more prevalent intensification strategies to address secondary loss of response (LOR) in inflammatory bowel disease (IBD). Hence this study aimed to prospectively compare infliximab RI and 6-weekly dose interval shortening (DIS) with reference to clinical and pharmacokinetic effectiveness, and to identify early predictors of response.

Methods
A prospective multicentre parallel cohort study of consecutive patients with IBD who underwent dose intensification to address secondary LOR using (1) infliximab RI (i.e. repeat week 0,2,6 dosing) followed by 8-weekly maintenance, or (2) 6-weekly DIS, over 30 weeks (6 doses) was undertaken. Primary outcomes were: (1) Clinical response, defined as a decrease in Harvey Bradshaw Index ≥3 or partial Mayo score ≥2 from pre-intensification baseline, assessed at weeks 12 and 32, and (2) Clinical and pharmacokinetic predictors of week 32 response, with serum infliximab samples collected at predefined timepoints (Figure 1). Patients who were dose intensified in the absence of clinical symptoms, were excluded from the primary analysis.

Results
Of 104 patients, 54 underwent RI and 50 underwent 6-weekly DIS (Table 1), including 43 patients from each cohort who were dose intensified to address clinically active disease. Baseline infliximab trough levels prior to RI and DIS (2.03 v 2.02ug/ml, p=0.83) were comparable. Clinical response was similar across both RI and DIS cohorts at weeks 12 (70 v 65%, p=0.89) and 32 (53 v 63%, p=0.51). Multivariate logistic analyses demonstrated that objectively verified active disease at baseline (OR 20.43[2.53–64.94]; p=0.005) and clinical response at week 12 (OR 15.44[1.20–19.97]; p=0.036) were associated with week 32 response, as were week 2 infliximab levels within the RI cohort only (OR 1.34[1.02–1.47]; p=0.036). Following RI, week 2 infliximab levels below 15.6ug/ml (sensitivity 100.0%; specificity 42.9%; AUROC 0.76; p&lt;0.05) were predictive of not achieving clinical response at week 32; potentially indicating that amongst this patient subset, week 12 clinical response may be useful in differentiating between early clinical responders who may benefit from sequential DIS following RI to prevent subsequent non-response, and early clinical non-responders who may benefit from early biologic switching.

Conclusion
Despite similar clinical outcomes across both dose intensification strategies, only upfront dose intensification using infliximab RI was associated with early clinical and pharmacokinetic predictors of response capable of facilitating early dose optimisation and biologic switching.
P465 Is golimumab serum level predictive of clinical remission after intensification for loss of response in patients with ulcerative colitis?
Authors: Fumery M , Nancey S , Filippi J , Altwegg R , Hebuterne X , Boschetti G , Veyrard P , Yzet C , Paul S , Roblin X 
Published: January 2022

Abstract

Background
Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was therefore to determine a threshold of serum golimumab before intensification predictive of clinical remission after optimization.

Methods
We included consecutive patients with UC and loss of response to golimumab (Mayo score between 6 and 12 and an endoscopic Mayo sub-score&gt; 1) in a prospective multicentric cohort. Patients with loss of response at 50 mg / 4 weeks (W) and 100 mg / 4W underwent therapeutic intensification at 100 mg / 4W and 100 mg / 2W, respectively. Patients were followed prospectively with a first evaluation between weeks 2 and 4 (visit 2) and between weeks 4 and 8 (visit 3) after intensification. Clinical remission was defined by partial Mayo score ≤ 1. Serum level and anti-golimumab antibodies were evaluated at each visit (Lisa Tracker, Theradiag France).

Results
A total of 47 patients (female, 50%; median age, 39 years (IQR, 27–52) treated with golimumab for a median of 20.4 weeks (IQR, 10.7–38.3) were included. The median partial Mayo score was 6 (IQR, 5–7) and the endoscopic Mayo score was 3 (IQR, 2–3). The median golimumab serum level before intensification was 2.23 µg / mL (IQR, 1.02–3.96) and only three patients (6.2%) had anti-drug antibodies. After a total of 50 drug intensification, 23 (48.9%) patients had clinical response (100 mg / 4W: 14/25 (58.3%); 100 mg / 2W: 9/25 (36%)), 10 (21%) clinical remission and 18 (39%) endoscopic response. The median golimumab levels before intensification were respectively 2.17 µg / mL (IQR, 0.97–3.25) and 2.47 (IQR, 1.10–4.05) in responders and non-responders (p = 0.66), and 1.11 µg / mL (IQR, 0.59–2.29) and 2.47 µg / mL (IQR, 1.21–3.83) in patients with and without clinical remission after intensification (p = 0.054). In multivariate analysis, intensification to golimumab 100 mg / 2W (vs 100 mg / 4W) (OR, 0.11 [95%CI, 0.01 - 0.87], p=0.037) and change of golimumab level between V1 and V2 (OR, 1.48 [95%CI, 1.02 - 2.14], p=0.037) were significantly associated with clinical remission after intensification. Only one serious adverse event (infection) was reported during the 24-week follow-up.

Conclusion
In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Change of golimumab level was predictive of clinical remission after intensification.