bluuebunny/crossref_metadata_2025_split huggingface dataset:
P440 Prevalence of NUDT15 polymorphisms and incidence of thiopurine-induced leukopenia in Inflammatory Bowel Disease patients: A systematic review and meta-analysis
Authors: Yu N , Sriranganathan D , Walker G J , Sazonovs A , Wilding H , Kennedy N A , Ahmad T , Boyapati R K , Segal J P , Ding N J S 
Published: January 2023

Abstract

Background
Nudix hydrolase 15 (NUDT15) genetic polymorphisms confer an increased risk of thiopurine-induced myelosuppression (TIM). Thiopurines continue to be widely used as maintenance therapy for inflammatory bowel disease (IBD) in patients worldwide. However, the global prevalence of NUDT15 variants and incidence of TIM in IBD remains unclear. We aimed to evaluate the global prevalence of NUDT15 polymorphisms in IBD patients and incidence of thiopurine-induced leukopenia in patients with these polymorphisms.

Methods
We searched Medline, Embase, Emcare, CINAHL, APA PsycInfo and the Cochrane Library databases from inception until 7 July 2022. Full-text articles and conference abstracts reporting the frequency of any NUDT15 polymorphism and/or frequency of leukopenia in adult IBD patients with these variants, were included. Studies that examined paediatric populations or mixed disease populations, or reported duplicate data, were excluded. A random effects model was performed to estimate the pooled prevalence of NUDT15 variants, pooled prevalence of early (≤8 weeks) and late (&gt;8 weeks) leukopenia and relative risk (RR) of developing leukopenia.

Results
20 studies comprising 5232 IBD patients were included. The pooled prevalence of the *1/*1 wild type genotype was 83% (95% CI: 0.78-0.88). The pooled prevalence of the *1/*3 c.415C&gt;T C/T variant was 13% (95% CI: 0.10-0.18), *3/*3 c.415C&gt;T T/T variant was 2% (95% CI: 0.01-0.02), *1/*5 c.52G&gt;A G/A variant was 2% (95% CI: 0.01-0.03) and *1/*6 c.36_37insGGAGTC ins/- variant was 7% (95% CI: 0.04-0.12). Subgroup analyses showed a higher pooled prevalence of the *1/*3 c.415C&gt;T C/T variant in Japanese (20%, 95% CI: 0.16-0.24) and Chinese patients (18%, 95% CI: 0.12-0.27). Patients with the *1/*3 c.415C&gt;T C/T variant had a RR of 4.12 (95% CI: 2.87-5.91) of developing leukopenia relative to the *1/*1 genotype, and the pooled prevalence of early leukopenia was 20% (95% CI: 0.16-0.26) and late leukopenia was 36% (95% CI: 0.26-0.49). Patients with the *3/*3 c.415C&gt;T T/T variant had a RR of 9.38 (95% CI: 5.17-17.01) of developing leukopenia relative to the *1/*1 genotype, and the pooled prevalence of early leukopenia was 99% (95% CI: 0.07-1.00). The pooled prevalence of early leukopenia was 49% (95% CI: 0.29-0.69) in patients with the *1/*6 c.36_37insGGAGTC ins/- variant.

Conclusion
NUDT15 polymorphisms are common in IBD patients and strongly predict thiopurine-induced leukopenia. The most common variant was the *1/*3 c.415C&gt;T C/T variant and the *3/*3 c.415C&gt;T T/T variant was associated with the highest risk of leukopenia. Pre-treatment genotyping for NUDT15 variants should be considered particularly in Asian populations, to guide individualised thiopurine dosing and avoid myelotoxicity.
P450 Real life Effectiveness and safety of an induction treatment with tofacitinib in patients with Ulcerative Colitis: First results of the French TOFAST cohort
Authors: Fumery M , Bouhnik Y , Faure P , Bouzidi A , Brault Y , Peyrin-Biroulet L , Laharie D 
Published: January 2023

Abstract

Background
We report the results of TOFAST, a French ongoing prospective observational multicenter study, evaluating the clinical benefit of tofacitinib for the treatment of moderate to severe UC.

Methods
In this descriptive interim analysis, effectiveness and safety were assessed at the end of induction therapy (up to 4 months after tofacitinib initiation). Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥ 30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore &gt;1. Change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to patient relief were also analyzed.

Results
Among the 102 patients included, 86 had available data at the first follow-up visit, corresponding to the end of induction period. At inclusion, 53.9% of patients were male with a mean (± SD) age of 37.1 ±13.6 years, a median disease duration of 6.1 years [Q1; Q3: 2.8; 10.8]. 48% of patients had pancolitis and 24.5% an extraintestinal manifestation; mean PMS was 6 ±1.8 with median SF and RB scores of 3.0 [Q1; Q3: 2.0; 3.0] and 2.0 [1.0; 2.0], respectively. Regarding prior drug exposure, 92.2% of patients had received at least one anti-TNF agent, 62.7% vedolizumab and 34.3% ustekinumab. Tofacitinib was initiated at 10 mg b.i.d, in combination with 5-ASA and corticosteroids for 19.6% and 33.3% of patients, respectively. At the first follow-up visit (median 1.9 months after treatment initiation), tofacitinib was ongoing in 87.2%, mostly (73.3%) at 10 mg b.i.d. Corticosteroids were ongoing in 29.1% of patients.
At the end of induction period, rates of clinical response and remission were 52.3% and 43%, respectively. Median changes in RB and SF scores were identical at days 7 and 14, -1 point [Q1; Q3: -1.0; 0.0] and -1 point [Q1; Q3: -2.0 - 0.0], respectively. For patients who reported improvement (68.6%), the median time to relief was 7 days [Q1-Q3: 4.0-15.0].
PRO2 scores normalisation during the first 14 days is shown in the figure.
RRegarding safety, 73.5% of patients reported at least one adverse event (AE) and 12.6% reported at least one serious AE. Ten (9.8%) infections (none considered as serious) and 2 (1.9%) Herpes Zoster were reported. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table).

Conclusion
The interim results of TOFAST study show that at the end of induction therapy with tofacitinib, 52.3% of patients achieved clinical response and &gt;40% achieved remission. Rapid improvement in SF and RB scores was observed within 2 weeks. AEs were consistent with the known tofacitinib safety profile.
P454 No increased postoperative risk of venous thromboembolism nor infectious complications after JAK inhibitor exposure in patients with ulcerative colitis undergoing colectomy
Authors: De Greef I , Bislenghi G , Terrasson I , Sabino J , Ferrante M , D'Hoore A , Vermeire S , Verstockt B 
Published: January 2023

Abstract

Background
Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolism (VTE), in patients who already have a 2 to 4-fold risk for thromboembolic events. In light of recent concerns on increased major adverse events associated with JAK inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other (non)infectious complications in UC patients undergoing colectomy after JAK inhibitor use.

Methods
This retrospective cohort study included all UC patients who underwent colectomy between 2013 and 2021 in our tertiary IBD center, and documented the 180-day postoperative non-infectious and infectious risks (table 1). Clinically relevant information included patient demographics, comorbidities, family history of IBD, personal history of VTE, intake of oral anticonception, smoking behaviour, disease characteristics including indication for colectomy, preoperative serum laboratory values, perioperative drug exposure (table 2) and surgical characteristics including low-molecular weight heparin (LMWH) prophylaxis (table 3).

Results
One-hundred seventy-nine UC patients (43.6% women, median [IQR] age 42.0 [28.5 – 56.2] years) underwent colectomy due to refractory disease (n=154) or suspected dysplasia or carcinoma (n=25). Forty-nine patients (27.4%) were operated urgently. In the twelve weeks prior to surgery, 55 (30.7%) patients had received anti-TNF agents, 40 (22.3%) anti-adhesion therapy, 16 (8.9%) anti-IL12/23, 2 (1.1%) investigational agents and 36 (20.1%) JAK inhibitors. Preoperatively, 27 patients (15.1%) were administered a moderate to high dose of systemic corticosteroids. All patients received antithrombotic prophylactic LMWH postoperatively, except for two patients who developed a gastrointestinal bleeding. During the 180-day postoperative period, a total of 3 patients (1.7%; mean age 51 years, 1 female) developed an intra-abdominal thrombosis, found by coincidence on CT scan. In all patients risk factors were identified, e.g. inflammatory state, cancer, high dose of corticosteroids. No VTE was seen in the patients who underwent colectomy while on JAK inhibitor. Only two out of 36 JAK inhibitor treated patients (5.6%) developed an infectious complication, while the overall risk of developing an infectious complication was 19.5%.

Conclusion
The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. We did not observe any VTE in patients who were exposed to JAK inhibitors prior to surgery, nor did we see an increased risk on short-term infectious complications in this patient group. All patients who developed VTE despite LMWH had additional risk factors.
P456 Magnetic resonance enterography findings at week 46 after biological treatment predict long-term clinical outcomes in Crohn’s disease patients
Authors: Fernandez Clotet A , Ordás I , Masamunt M C , Caballol B , Rodriguez S , Panés J , Ricart E , Rimola J 
Published: January 2023

Abstract

Background
Magnetic resonance enterography (MRE) provides an accurate evaluation of transmural lesions in Crohn’s Disease (CD). However, MRE findings associated with poor long-term outcomes in CD are not yet defined. Identification of such parameters would help in defining therapeutic goals.

AIMS
to identify predictors of long-term clinical outcomes based on MRE findings performed 46 weeks after biological treatment initiation in patients with CD.

Methods
single-center, prospective, longitudinal study conducted from 2010 to 2019. Patients with CD who had an MRE evaluation 46 weeks after biological treatment initiation and clinical follow-up of at least 3 years were evaluated.

Results
89 patients were included with a median follow up of 53 months (IQR 44-76). 59 patients had ileal (66.3%), 26 ileocolic (29.2%) and 4 colonic disease (4.5%). 31 (34.8%) had inflammatory behavior, 27 (30.3%) stricturing, 9 (10.1%) fistulizing and 22 (34.7%) stricturing/fistulizing. 70 (78.7%) were treated with anti-TNFα, 5 (5.6%) vedolizumab and 14 (15.7%) ustekinumab. During follow-up, 25 (28.1%) required surgery, 17 (19.1%) hospitalization, 40 (44.9%) had clinical relapse (CDAI &gt;150), 12 (13.5%) required corticosteroids and 12 (13.5%) required endoscopic dilatation. 32 (36.0%) patients needed resection surgery or endoscopic dilatation. MaRIA score ≥11 in any segment at week 46 was associated with a higher risk of surgery [HR 6.28 (1.42-27.84), p=0,02] or surgery/endoscopic dilatation [HR 3.76 (1.24-11.38), p=0,02]. Relative contrast enhancement (RCE) &gt;103 was associated with higher risk of clinical relapse [HR 1,01 (1.00-1.02), p=0,03] and corticosteroids requirement [HR 1,01 (1.00-1.02), p=0,05].

Conclusion
MRE findings at week 46 after biological treatment initiation predict long-term clinical outcomes in CD patients. The main determinants of poor clinical prognosis were MaRIA score ≥11 and RCE &gt;103. Patients with these persistent findings may be candidates for treatment optimization.
P457 Treatment duration of ustekinumab in patients with Crohn’s disease (CD) and psoriasis (PSO) – real-world evidence from German claims data
Authors: Kosa F , Nair S , He J , Lin X , Di Scala L , Lehne M , Ghiani M , Maywald U , Wilke T 
Published: January 2023

Abstract

Background
Ustekinumab is a monoclonal antibody approved for the treatment of inflammatory diseases such as Crohn’s disease (CD) or psoriasis (PSO). Real-world evidence about treatment persistence of patients treated with ustekinumab is scarce. This retrospective observational study uses German claims data to analyse average treatment duration of ustekinumab in CD and PSO patients in a real-world setting.

Methods
Patients with at least two confirmed outpatient diagnoses or one inpatient diagnosis of Crohn’s disease (ICD-10 code: K50*) between 01/01/2016 and 30/06/2020 and a subsequent incident prescription of ustekinumab (ATC code: L04AC05) between 01/01/2017 and 30/06/2020 were identified in the AOK PLUS database, a sickness fund with more than 3.4 million patients from the states of Saxony and Thuringia in the eastern part of Germany. Similarly, patients with at least two outpatient diagnoses or one inpatient diagnosis of psoriasis (ICD-10 code: L40*) between 01/01/2010 and 30/06/2020 and an incident prescription of ustekinumab between 01/01/2011 and 30/06/2020 were identified. Treatment durations were quantified by assessing the time from the first ustekinumab prescription until treatment discontinuation. Discontinuation was defined as a gap of at least 90 days between the end date of the last prescription and the date of the next prescription or switch to another biologic agent. Deaths were counted as treatment discontinuations, and patients were censored at the end of follow-up or disenrolment from the sickness fund. Stockpiling was taken into account (i.e., accumulated medications were assumed to be taken consecutively), and hospitalizations were considered as a part of treatment. Treatment duration was explored in a Kaplan-Meier analysis.

Results
A total of 251 CD and 848 PSO patients with incident ustekinumab treatment were identified. 39 CD (15.5%) and 375 PSO patients (44.2%) discontinued treatment during the study period (median follow-up: 16.1 and 44.9 months; total patient years: 383.6 and 3338.7 for CD and PSO, respectively). For CD, median time to treatment discontinuation was not reached, as most patients were still on treatment at the end of the follow-up period; for PSO, median time to treatment discontinuation was 51.5 months (Table 1 & Figure 1).

Conclusion
Our results provide real-world evidence of ustekinumab treatment duration in patients with CD and PSO in Germany. A low proportion of CD patients discontinuing treatment over the available follow-up period and a median treatment duration of more than four years for PSO indicate that ustekinumab treatment persistence is high in these patient groups.
P458 Low adherence to Mediterranean diet is associated with increased adipose tissue in patients with ulcerative colitis (UC) after pouch surgery: a cross sectional study
Authors: Pfeffer-Gik T , Godny L , Ollech J , Wasserberg N , White I , Cohen S , Broitman Y , Avni-Biron I , Banai H , Snir Y , Yanai H , Yackobovich Gavan M , Shimon I , Tsvetov G , Barkan R , Dotan I 
Published: January 2023

Abstract

Background
Obesity [body mass index (BMI) ≥30 kg/m2 ] prevalence in patients with inflammatory bowel diseases (IBD) ranges between 15-40%. Dual-energy x-ray absorptiometry (DEXA) is the gold standard for body composition evaluation. Patients with ulcerative colitis (UC) who undergo total proctocolectomy and pouch surgery may develop small bowel inflammation (pouchitis) resembling Crohn's disease (CD). We aimed to assess body composition of patients with UC-pouch and potential risk factors for high adiposity.

Methods
Patients with UC-pouch ages 18-50 were recruited. Adipose tissue was assessed by DEXA (increased adipose tissue defined as &gt; 26% male, &gt;31% female), sarcopenia- assessed by hand-grip (defined as &lt;30 kg male, &lt;20 kg female). Clinical data, biochemical and inflammatory markers documented, Mediterranean diet adherence assessed by the Israeli Mediterranean diet (I-MEDAS) questionnaire.

Results
Recruited patients: 30: male/female 14/16; median age 45 (IQR 31-51.7) years; median BMI 23.2 (IQR 21-26.5); median pouch age 17 (IQR 10-25) years. One patient was obese (BMI ≥ 30 kg/m2) and seven-overweight (BMI 25-29.9 kg/m2). Median fat percentage 34.7 (IQR 30.1-39.7); 23/30 (76.6%) had increased adipose tissue. 14/30 (46%) patients were defined as normal weight obesity- normal BMI with increased adipose tissue. In univariate analysis comparing males to females, age and I-MEDAS score were comparable. Females were less physically active (p=0.028), had lower BMI (p=0.043), and higher rates of elevated adipose tissue (p=0.002). In multivariate analysis adherence to the Mediterranean diet was associated with lower adipose tissue regardless of sex and BMI (p&lt;0.001). Sarcopenia was found in 1 (3.33%) female patient.

Conclusion
Patients with UC-pouch are at risk for "Normal-weight obesity", an uprising health concern, having increased adipose tissue regardless of BMI and sarcopenia. Adherence to the Mediterranean diet is inversely associated with increased adiposity, and may be used to modify adiposity in patients with UC after pouch surgery, irrespectively of BMI.
P459 Hospitalization, use of biologics and surgery rates in inflammatory bowel diseases: a single-center comparative analysis between public and private healthcare systems in a tertiary unit from Latin America
Authors: Zacharias P , Perussolo M , Magro D O , Barauna F D S B , Kotze P G 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation of the intestine, have a rising incidence and prevalence globally. The potential impact of socioeconomic inequality on health and mortality is well documented. In chronic diseases, the effect of inequality in assessment to healthcare can be associated with a higher frequency of complications and worse organ functionality in patients with social deprivation. In IBD, there are scarce studies comparing the differences between patients according to their socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems.

Methods
single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private healthcare systems. Main analyzed variables were age at diagnosis, gender, Montreal classification, new diagnoses or referred patients, smoking status, previous medications, need for IBD-related hospitalizations and abdominal surgery. Demographic characteristics, hospitalizations, need for surgery and biologics were compared between two subgroups: private and public healthcare systems.

Results
500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgical procedure, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs. 43.97%, p=0.014). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%, p=0.33) as well as the rates of colectomy (public: 16.83%, private: 19.48%, p=0.65). Biologics were used almost twice as often in private as compared to the public system (45.45% vs. 22.77%, p=0.001).

Conclusion
Patient demographics were overall similar between healthcare systems in IBD patients. There were no differences in the rates of hospitalization and abdominal surgery between the two subgroups in both diseases. In patients with UC, there was greater use of biological therapy in the private healthcare setting. Global data regarding the possible impact of social deprivation in IBD-related outcomes are warranted.
P461 Rapid response to appendectomy in the majority of patients with refractory Ulcerative Colitis
Authors: Adamou A , Bercher M , Iesalnieks I , Streetz K ,   Department of Surgery
Published: January 2023

Abstract

Background
Appendectomy is suggested to improve the course of the disease in many patients with refractory Ulcerative Colitis (UC). Present prospective observational study demonstrates short-term outcomes after an appendectomy in 16 patients with refractory UC.

Methods
Between 5/2022 and 11/2022, 16 selected patients underwent appendectomy for refractory UC. Only patients with dysplasia or cancer were excluded. However, an appendectomy was not proposed to patients with severe sarcopenia or severe anemia, except in one case of severe acute colitis. The appendectomy was performed without the removal of the cecal base.

Results
Mean age was 35 years (18 to 59 years), there were 9 male patients. Nine had a pancolitis. Eight patients were referred to colectomy (50%). Eight were taking steroids (10mg to 75mg), all but three were under biological treatment. Median preoperative Mayo score was 6.5. Two patients had severe anemia (hemoglobin &lt;10 g/dl). The appendix appeared to be inflamed visually in 3 patients (19%) and histologically in 10 patients (62%). Hospital stay was median 2 days, there was one wound infection at the port site. A significant improvement of disease symptoms was reported by 14 patients during the first 2 weeks. At the end of the follow-up period of 1 to 6 months, no colectomy has been performed.

Conclusion
The majority of patients with refractory UC demonstrates rapid clinical response to an appendectomy. Longer observation is necessary in order to determine whether the rapid response translates to a favourable long-term outcome.