bluuebunny/crossref_metadata_2025_split huggingface dataset:
P470 Real-world characteristics and complications of patients with Ulcerative Colitis receiving conventional therapy in the public healthcare system in Brazil
Authors: Galhardi Gasparini R , Yukie Sassaki L , Lima Martins A , Saad Hossne R , Watanabe de Oliveira R , Yang Santos C , Biatti Barreto T 
Published: January 2022

Abstract

Background
Ulcerative colitis (UC) therapy management is complex and typically begins with conventional therapy (CVT) followed by biologic drugs. For many years, CVTs were the only available option for the treatment of UC in the public healthcare system in Brazil (SUS). Biologic therapy was only available at the end of 2020. This study aimed to observe the real-world intestinal complications (IC) experienced in patients with UC receiving CVT in SUS.

Methods
This study was a secondary analysis of patients (&gt;18 years) with UC (ICD-10 code: K51) who received at least two claims of CVT (index data defined as first CVT), between January 2011 and February 2020, in the DATASUS database. UC IC was defined as at least one claim (after index date) for either: UC-related hospitalisation, pre-defined procedure codes for rectum or intestinal surgeries, pre-defined ICD-10 codes were validated by independent clinical experts (malignant neoplasia of colon, stenosis, haemorrhage, ulcer and other rectum and anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Patients with an anal or rectal fissure or fistula, with &lt;6 months of follow-up from index date, with a CVT claim 12 months before index date or patients treated outside of the public healthcare system, were excluded. Descriptive statistics, annual incidence and incidence rate (IR; per 100 patient-years [PY]) over the available follow-up period were calculated.

Results
In total, 41,229 patients with UC were included (median age, 48 years; 65% women) and the median (interquartile range [IQR]) follow-up period was 3.3 (1.8 - 5.3) years. CVT utilized during follow-up was: mesalazine (87%), sulfasalazine (15%), azathioprine (16%) or methotrexate (1%); the median (IQR) CVT duration was 1.9 (0.8 – 4.0) years. The overall IR of IC was 2.5 per 100 PY during the follow-up period. Of the IC, 54% were related to ICD-10, 20% were related to a procedure and 26% to a UC-related hospitalisation (Table 1).

The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after index, respectively (Table 2).

Over the first 3 years, the annual IR of UC-related hospitalisations ranged from 0.8% to 1.1%, for ICD-10 related events 0.9%-1.2% (anus and rectum disease, and malignant neoplasia of colon most frequently reported) and for procedure-related events 0.6%-0.7% (intestinal resection and polyp removal were the most frequent procedures).

Conclusion
The IR of IC was constant along the use of CVT. This study suggests the need to consider additional strategies for intestinal complications associated with the management of UC in Brazil, including but not limited to biologics.
P498 Sources of excess steroid prescriptions and clinical adverse outcomes associated with steroid excess: The Leeds Steroids study
Authors: Rosiou K , Carbonell J , Dolby V , Monfared N , Selinger C 
Published: January 2022

Abstract

Background
This retrospective study aims to determine steroid prescription practice across primary and secondary care, quantify the proportion of primary care prescriptions communicated to secondary care, and assess outcomes associated with excessive steroid use.

Methods
The study cohort consists of all patients attending IBD clinics under Leeds Teaching Hospitals from 1/1/2016 to 31/12/2017 with linked primary care records. Data were extracted from the hospital’s electronic health record. Steroid excess was defined based on ECCO guidelines. Cases with excess were reviewed to determine if escalation was implemented, appropriateness of escalation, timeliness of that (within 6 weeks of steroid course) and whether steroid excess was unavoidable.

Results
2246 patients were included in the study (Mage: 47.26 y; 47.6% male; 46.4% CD, 46.8% UC; 36.2% of CD patients on thiopurines, 26.3% on biologics; 78.8% of UC patients on 5-ASA, 21.4% thiopurines, 5.6% biologics). During the study period 32.9% of patients were exposed to steroids (77.4% of steroid prescriptions issued for IBD, 27.5% of prescriptions for IBD originating from primary care).
Significantly more prescriptions from secondary care were of appropriate dose and duration compared to primary care (84.7% vs 40.7%, p&lt;0.001). Secondary care was made aware within six weeks of steroid initiation in 60.3% of steroid courses prescribed by primary care. 49.5% of patients flared after being prescribed steroids from primary care, compared to 39.1% from secondary care, p=0.003.
Steroid excess was observed in 14.5% of patients and was related to IBD in 76% of them. In patients with steroid excess due to their IBD; excess was acted upon in 82.8% of patients (77.5% had treatment escalation). Escalation was considered appropriate in 98.9% of patients however, it was timely in 62.4% of patients and steroid excess was unavoidable in 47.6%.
Patients with steroid excess due to IBD had significantly more hospital admissions for IBD (p&lt;0.001), hospital admissions for infections (p=0.036) and more antibiotic courses prescribed by GP (p=0.023) compared to patients without steroid excess.

Conclusion
Steroid prescribing for IBD flares originating from primary care is common however, steroid dose and duration are frequently inappropriate, and more than one third of courses are not communicated to secondary care in a timely manner. A significantly higher amount of patients flare again after being prescribed steroids by primary care. Finally, over 50% of steroid excess is potentially avoidable and steroid excess is related to negative consequences such as IBD admissions, admissions for infections and antibiotic prescriptions.
P499 Accessing ultrasonographic transmural healing in patients with Crohn’s disease after induction therapy with infliximab: should we aim for higher infliximab trough levels?
Authors: Morão B , Frias Gomes C , Revés J , Cúrdia Gonçalves T , Freitas M , Castro F , Moreira M J , Cotter J , Pereira F , Caldeira A , Sousa R , Coelho R , Macedo G , Macedo C , Ferreira M , Glória L , Torres J , Palmela C 
Published: January 2022

Abstract

Background
Higher infliximab trough levels (ITL) have been shown to be associated with better rates of clinical remission and mucosal healing. Transmural healing (TMH) assessed by cross-sectional imaging [such as intestinal ultrasound (IUS)] is emerging as a potential target in Crohn′s disease (CD) treatment, but whether there is any relation with ITL remains unclear. Our goal was to investigate the association between ITL and bowel wall thickness (BWT) in patients with CD after induction therapy with IFX.

Methods
Prospective multicentric cohort study of CD patients who started IFX in mono or combination therapy. Patients performed IUS and ITL at weeks 0 and 14. TMH was defined as BWT ≤3 mm in the most affected segment. A ROC curve was plotted to determine the best cut-off point of ITL to predict TMH. Chi-square test, Mann-Whitney test and Spearman correlation were performed to assess the ITL relation with BWT.

Results
We included 57 patients, 30 (53%) of whom were men with mean age of 36±15 years. Disease extension according to Montreal classification was L1 in 19 (33%), L2 in 8 (14%) and L3 in 30 (53%) patients; 6 (11%) patients also had L4 extension and 19 (33%) patients had perianal disease. Disease behavior was B1 in 36 (63%), B2 in 13 (23%) and B3 in 8 (14%) of patients. Most patients (61%) were under immunomodulators and 15 (26%) were under corticosteroids when infliximab was started; most (88%) were naïve for infliximab. At week 0, all patients had endoscopic activity and 97% had increased BWT at the most affected segment. The most affected segment on IUS at week 0 was the terminal ileum in 38 (67%) patients and the ascending, transverse, descending and sigmoid colon in 5 (9%), 2 (3%), 7 (12%) and 5 (9%) patients, respectively. There was a very good agreement between IUS and colonoscopy for evaluation of the most affected segment at baseline (kappa 0.81, p&lt;0.001). Median ITL at week 14 was 4.30 μg/ml (IQR 0.01–21). TMH at week 14 was achieved in 13 (23%) patients. ITL and BWT at week 14 were negatively correlated, with a fair correlation (r=-0.3, p=0.03). The AUC of ITL for BWT was 0.661 (best cut-off value 7.65, sensitivity 54%, specificity 89%). ITL ≥7.65 μg/ml was associated with higher rates of TMH (44% vs 15%, OR 4.47 [95%CI 1.2–16.4], p=0.04).

Conclusion
In our cohort of CD patients completing induction therapy with infliximab, higher ITL were associated with higher ultrasonographic transmural healing rates. The best cut-off for predicting TMH was ITL above 7.65μg/ml.
P507 Need for surgery in patients with ulcerative colitis in the era of biologic therapy
Authors: Zamora Olaya J M , Aparicio-Serrano A , Gómez Pérez A , Ortiz Chimbo D S , Rodríguez Tirado M I , Soto Escribano P , Marín Pedrosa S , Iglesias Flores E , Benítez J M 
Published: January 2022

Abstract

Background
The aim of the present study is to evaluate the impact of anti-TNF drugs on the need for surgery among patients with ulcerative colitis (UC). Secondary objectives: to compare needs for medical treatment before surgery, indications for surgery and surgery-free survival.

Methods
Observational, retrospective and single-center study that includes patients with UC who have required surgery for inflammatory bowel disease (IBD). Two cohorts of UC patients were analyzed: cohort-1 (pre-antiTNF) with a diagnosis of UC between 1995–2000, and cohort-2 (post-antiTNF) diagnosed after the approval of anti-TNF between 2010–2015. Patients were followed up to the event (surgery) or at least five years since UC diagnosis. Demographic variables related to UC and surgery were collected. Kaplan-Meier curves were performed to compare the surgery-free survival in both cohorts. The ENEIDA registry was used to identify the patients.

Results
A total of 32 patients underwent surgery were included (18 in cohort 1 and 14 in cohort 2). The mean age at UC diagnosis was significantly lower in cohort 1 (31.3 vs 46.4 years, p=0.015), and the proportion of smoking patients was higher in cohort 1 (27.8% vs 0%, p=0.053). There were no differences between the two cohorts in the extent of UC and extraintestinal manifestations. Surgery rates were 3.7% in cohort-1 and 4.7% in cohort-2. Overall, there were no differences in colectomy rates in both cohorts (Figure 1). However, the median time from UC diagnosis to surgery was significantly longer in cohort-2 (21 vs. 1 months, p&lt;0.05) (Figure 2). Regarding the surgery timing, the proportion of urgent surgery was higher in cohort-1 (61% vs 43%, ns); while in cohort-2, scheduled surgery predominated (50% vs 18%, ns). In the subgroup of patients who underwent scheduled surgery, the surgery free time was significantly longer in cohort-2: 67 vs 12 months (p=0.01) (Figure 3). Regarding surgical indications, cohort-1: 78% acute severe colitis or acute complications and 22% refractory to medical therapy; cohort-2: 43% Acute Severe Colitis/complications. A high proportion of patients in both cohorts required ostomy (temporary or definitive). Pre-surgery medical treatment needs cohort-1 vs cohort-2: steroids (100% vs 71%, p=0.028), immunosuppressants (5.6% vs 57%, p=0.002).

Figure 1. Surgery -free survival at 5-years follow-up.

Figure 2. Kaplan-Meier curves of time from UC diagnosis to surgery.

Figure 3. Kaplan-Meier curves of time until scheduled surgery.

Conclusion
Surgery rates in UC patients remain stable in the post-antiTNF era. However, the arrival of antiTNF drugs allows a longer surgery-free survival, lower preoperative steroids requirements and less need for urgent surgery.
P514 Optimising response to infliximab in the management of perianal Crohn’s disease
Authors: Shah R , Anandbaskaran S , Hart A , Tozer P 
Published: January 2022

Abstract

Background
Perianal Crohn’s Disease (PCD) remains a refractory phenotype of Crohn’s Disease (CD)1. Despite initial demonstration of the benefit of infliximab (IFX) in PCD over 20 years ago2, it remains clear how IFX treatment can be optimised for PCD patients3. In this retrospective observational study, a cohort of PCD patients based at St Mark’s Hospital was reviewed to understand their disease-journeys whilst on treatment with IFX.

Methods
A cohort of 59 patients with PCD on treatment with IFX as of January 2020 were identified from a prospective database of IFX treated patients. Twenty-seven patients were classed as fluctuating IFX levels and underwent disease-journey analysis. Detailed qualitative analysis of individual patients journeys were carried out to correlate IFX levels, where available, to C-Reactive Protein (CRP), Magnetic Resonance Imaging (MRI) and Examinations Under Anaesthetic (EUA). These journeys were then graphed as a timeline for each of these patients.

Results
Four disease-journeys have been selected to exemplify key learning points in the management of PCD.
Graph 1: Improving drainage and reducing inflammatory burden with EUA can help to recover IFX levels and regain disease control. This suggests a well-timed EUA can have a synergistic effect on treatment with IFX.

Graph 2: In a subgroup of patients, optimised medical therapy with IFX alone remains adequate to perianal fistula healing.

Graph 3: Patients may benefit from temporary dose escalations with IFX to recapture response and to improve disease burden.

Graph 4: Some patients require longer periods of dose-escalated therapy as seen in this graph & higher IFX levels may be required for radiological healing.

Conclusion
These cases highlight interesting learning points and can help to manage complicated PCD patients. Further work is needed to determine how significant the link is between improvement in IFX levels post-EUA and how this correlates with the overall clinical picture of the patient.

References
1. Sahnan K, Adegbola SO, Fareleira A, Hart A, Warusavitarne J. Medical-surgical Combined Approach in Perianal Fistulizing Crohn’s Disease (CD): Doing it Together. Curr Drug Targets. 2019;20(13):1373–1383.
2. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398–405.
3. Kotze PG, Shen B, Lightner A, Yamamoto T, Spinelli A, Ghosh S, Panaccione R. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut. 2018 Jun;67(6):1181–1194.
P518 Partial enteral nutrition use for Crohn’s disease management: a systematic review
Authors: Jatkowska A , White B , Gkikas K , Seenan J P , MacDonald J , Gerasimidis K 
Published: January 2022

Abstract

Background
Exclusive enteral nutrition (EEN) is an established treatment for the induction of clinical remission in children with active Crohn’s disease (CD). However, the benefit of partial enteral nutrition (PEN), in which only some diet is replaced with enteral nutrition, is not well-documented for the management of CD. This review explored the effectiveness of PEN as sole or adjunctive induction and maintenance therapy in patients with CD.

Methods
The protocol for this review was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/ protocol ID: CRD42021239325). Literature search was conducted using PubMed, Ovid Embase, Cochrane Controlled Register of Trials and Cumulative Index to Nursing and Allied Health Literature electronic bibliographic databases. Eligible study designs included: randomised control trials (RCTs), prospective, retrospective, and case control studies. Level of evidence was assessed with CASP tools with an emphasis on study design, and assessment of compliance and objective disease activity biomarkers. Two researchers evaluated each paper separately and when needed, consensus was resolved by a third.

Results
56 articles met the inclusion criteria, grouped under the following 6 distinct areas for PEN use in CD: 1) induction treatment; 2) maintenance treatment; 3) prevention of post-operative recurrence; 4) prevention of loss of response (LOR) to anti-TNFα therapies; 5) nutritional rehabilitation; 6) improvement of quality of life (QOL). Low-quality evidence suggests PEN may improve disease activity in patients with active CD; treatment efficacy was observed to be better in studies using higher proportions of energy intake from PEN. Good quality evidence suggests PEN combined with exclusion diets may be effective in active CD. However, most available studies originated from a single research group, and the additional benefits of exclusion diets over PEN are unclear, particularly as most studies used either high PEN volumes (&gt;75% of energy requirements), or EEN prior to PEN initiation. Good quality evidence shows that PEN at high volumes (≥35–50%) may prolong medically or surgically induced remission and improve the nutritional status of patients with malnutrition or growth delay. Low-quality evidence suggests that PEN may improve response and remission rates to infliximab therapy in CD. Three retrospective studies found that concomitant PEN with anti-TNFα therapies could prevent LOR. Some evidence indicates that PEN is associated with better QOL in patients with active disease or in remission.

Conclusion
PEN may have a beneficial role in various aspects of CD management; however, more robust data including RCTs are needed before specific recommendations can be made.
P524 Compared efficacy of ustekinumab and anti-TNF agents as first-line biological therapy in luminal Crohn’s disease
Authors: Riviere P , Kanters C , Ni A , Pellet G , Hupe M , Aboulhamid N , Poullenot F , Bitton A , Zerbib F , Lakatos P , Afif W , Laharie D , Bessissow T 
Published: January 2022

Abstract

Background
Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of moderate to severe Crohn’s disease (CD) is lacking. The objective of this study was to compare the clinical remission rate at 3 months of patients treated by ustekinumab or anti-TNF agents as first-line biological therapy.

Methods
We conducted a two-center retrospective study including biologic-naïve patients starting either ustekinumab or an anti-TNF agent for CD between January 2016 and December 2019. The primary endpoint was clinical remission at 3 months after therapy initiation, defined as a Harvey Bradshaw Index (HBI) &lt; 4 without steroids, need for CD-related surgery or treatment discontinuation due to treatment failure or intolerance. Secondary endpoints were remission at 12 months and time to drug withdrawal. Patients treated with ustekinumab were matched 1:3 to patients receiving anti-TNF agents using a propensity score including age, CD duration, smoking status, CD location according to the Montréal classification and history of perianal disease.

Results
208 patients [104 (50%) female, median age (InterQuartileRange) 30 years (23–47)] were included, 156 (75%) patients starting anti-TNF (95 (45%) adalimumab and 61 (29%) infliximab) and 52 (25%) ustekinumab and followed for a median (IQR) duration of 39 (22–52) months. Median (IQR) CD duration was 21 (6–104) months and 45 (22%) patients had previously undergone a CD-related surgery. At inclusion, the median (IQR) HBI was 5 (2–8) and 83 (39%) patients were receiving oral corticosteroids.
After matching, remission rates at 3 months were 25/45 (56%) patients in the ustekinumab group versus 102/135 (76%) in the antiTNF group [p=0.01, odds ratio (OR) 0.40 (Confidence Interval (CI) 95% 0.20, 0.82)]. At 12 months, remission rates were 26/41 (63%) patients in the ustekinumab group versus 99/123 (81%) in the antiTNF group (p=0.03). No difference was observed in terms of time to drug withdrawal (p=0.25). Rates of drug persistence at 12 months were 89% in patients treated with ustekinumab and 87% in those treated with antiTNF, respectively. Similar rates of adverse events were observed in the two groups (13% versus 13%, p&gt;0.9). In the antiTNF group, 3/156 (2%) adverse events leading to hospitalization were observed compared to 0/52 (0%) in the ustekinumab group (p=0.6).

Conclusion
In this retrospective cohort, we found that anti-TNF agents as a first-line biological therapy led to higher rates of remission at 3 and 12 months in biologic-naïve patients with Crohn’s disease than ustekinumab.
P526 Measurement of thiopurine metabolites concentrations after one week of treatment does not predict treatment failure in Inflammatory Bowel Disease patients
Authors: Deben D , Van Moorsel F , Creemers R , Winkens B , Bus P , Pierik M , Simsek M , De Boer N , Wong D , Van Bodegraven A 
Published: January 2022

Abstract

Background
Conventional thiopurines such as azathioprine (AZA) and mercaptopurine (MP) remain drugs of choice in maintaining remission and corticosteroid sparing in inflammatory bowel disease (IBD). Early discontinuation of thiopurine therapy occurs frequently, due to slow onset of effect and a relatively high frequency of early adverse drug reactions (ADR). Some ADR such as hepatotoxicity and gastro-intestinal complaints are associated with the thiopurine metabolite concentrations 6-thioguanine nucleotides (6-TGN) or 6-methylmercaptopurine ribonucleotides (6-MMPR), in particular elevated 6-MMPR concentrations or unfavorable 6-MMPR/6-TGN ratios.
Early measurement of thiopurine metabolites may help to optimize thiopurine therapy in IBD. The aim of this study was to assess the predictive value of thiopurine metabolite measurement one week after thiopurine therapy initiation on discontinuation during the first three months of therapy.

Methods
This was a multicenter prospective observational study in the Netherlands. Consecutive IBD patients who initiated thiopurine therapy were included and measurement of thiopurine metabolites was performed after 7 days (6 – 8) of treatment (T1). Patients were monitored for 12 weeks to document occurrence of ADR and early treatment discontinuation. Switching to an alternative thiopurine or adding allopurinol (as co-medication) was also considered as treatment discontinuation (to prevent ADR). 6-MMPR concentrations and 6-MMPR/6-TGN ratios were separately analyzed (Mann-Whitney U-tests) regarding therapy discontinuation within 12 weeks. P-values of ≤0.05 were considered statistically significant.

Results
In total, 255 patients were included, of which 83 were excluded due to either missing blood samples on T1 (n=54), dose adjustments within 12 weeks (n=25) or a delayed T1 measurement (n=4). Of the remaining 172 patients, 79 patients were male (46%), 102 patients had Crohn’s disease (59%) and 157 patients were treated with MP (91%). In total, 88 (51%) patients continued thiopurine therapy and 84 patients (49%) discontinued therapy within 12 weeks. Median 6-MMPR concentrations (1,295 versus 1,589 pmol x 108 red blood cells) and 6-TGN/6-MMPR ratios (8.8 versus 11.4) did not differ significantly between patients who continued versus discontinued therapy within 12 weeks (Figures 1 and 2).

Conclusion
In this study thiopurine metabolites at T1 did not relate to discontinuation of thiopurine therapy within 12 weeks. We will conduct additional pharmacodynamic studies to corroborate our hypothesis that early metabolite measurements may be of individual patients’ benefit.