bluuebunny/crossref_metadata_2025 huggingface dataset:
P387 Different rate of transmural remission between first and second line of biologic treatment in Crohn's disease
Authors: De Sire R , Rispo A , Caiazzo A , Testa A , Nardone O M , Guarino A D , Olmo O , Calabrese G , Fierro G , Toro B , Cantisani N M , Ferrante M , La Mantia A , D'Alessandro E , Castiglione F
Published: January 2023

Background

Transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still scarce. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line.

Methods

From 2018 to 2021 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was <4. Endoscopic remission was defined when SES-CD was <2. Transmural remission was defined when BWT was <3 mm at a “per-patient” analysis. In accordance with recent literature, laboratory remission was defined when FC was <94 ug/gr.

Results

One hundred and forty-one CD patients (78 ADA, 31 VDZ, 32 UST) were included in the study. At T1, transmural remission rate was recorded in 39.7% of CD patients treated in first line with ADA, and in 22.5% and 18.7% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.7). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 32.2% and 31.2% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.9). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29% and 37.5% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.4). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 45.1% and 40.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.057; VDZ vs UST: p=0.7).

Conclusion

Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.
P391 Relative association of bowel urgency clinically meaningful improvement or bowel urgency remission versus stool frequency remission and rectal bleeding remission with improvement in Inflammatory Bowel Disease Questionnaire scores in patients with moderately-to-severely active Ulcerative Colitis: An analysis from LUCENT-1 and LUCENT-2 phase 3 clinical trials
Authors: Sands B E , Feagan B , Gibble T H , Keohane A , Eastman W , Traxler K , Schreiber S , Jairath V , Armuzzi A
Published: January 2023

Background

Bowel urgency is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC)1. However, limited information is available regarding its potential association with other patient reported outcomes. We assessed the association of bowel urgency clinically meaningful improvement (CMI) or bowel urgency remission with Inflammatory Bowel Disease Questionnaire (IBDQ) scores whilst adjusting for the potential confounding effects of stool frequency (SF) and rectal bleeding (RB) remission using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Methods

Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (UNRS) (0=no urgency to 10=worst possible urgency). Bowel urgency CMI was defined as ≥3-point decrease in UNRS compared to baseline and bowel urgency remission was defined as UNRS of 0 or 1.2 IBDQ scores (range: 32–224) were calculated; higher scores indicate better quality of life. Mediation analyses were performed to examine the relative association between direct effects of bowel urgency CMI and bowel urgency remission (separate predictors) and IBDQ scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at Week (W) 12 and 40 (W52 of continuous treatment).

Results

At W12 and W52, bowel urgency remission directly accounted for 44.8% and 32.5% improvement in IBDQ total score, respectively; 22.7% and 39.1% of improvement was mediated by RB remission and 32.5% and 28.4% by SF remission, respectively. At W12, bowel urgency remission resulted in the largest proportion of improvement in each of the IBDQ domain subscores, whereas at W52, RB remission had a greater confounding effect (Fig. 1A). At W12 and W52, bowel urgency CMI accounted for 70% and 57.3% improvement in IBDQ total score, respectively; 12.8% and 25.6% of effects were mediated by RB remission and 17.2% and 17.1% by SF remission, respectively (Fig. 1B). Bowel urgency CMI accounted for the largest proportion of association with improvement in each of the IBDQ domain subscores at both W12 and W52.

Conclusion

Improvements in IBDQ scores were primarily ascribed to bowel urgency remission and bowel urgency CMI relative to RB remission and SF remission, particularly at W12, in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ quality of life.

References:
P401 Concomitant azathioprine treatment effects vedolizumab treatment persistence in Crohn’s Disease but not in Ulcerative Colitis
Authors: Toruner M , Guvenir T , Er R E , Soykan I
Published: January 2023

Background

Vedolizumab is a monoclonal antibody against integrin α4β7 that is being used for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). Recent studies have shown conflicting results for the effect of concomitant azathioprine use with vedolizumab monotherapy. In this single center cohort study, we investigated the effect of concomitant azathioprine treatment on vedolizumab drug persistence in UC and CD treatment.

Methods

We performed a retrospective review of all adult (≥18 years) UC and CD patients started on VDZ at our infusion center. Data collection included baseline demographics, concomitant azathioprine therapy, VDZ therapy and disease activity scores using the partial Mayo score and Harvey Bradshaw Score. Data were obtained from the digital medical record. The primary outcome measure was VDZ persistence, represented in Kaplan-Meier analysis. This analysis assessed persistence on every 8 week dose regimen.

Results

This single center cohort included 142 VDZ treated UC (n=64) and CD (n=78) patients. All patients had a history of at least one anti-TNF treatment: Mean age 38.9±12.5 years and male gender 84 (59.2%). Median disease duration was 6±1.6 years. 6 Patients were excluded from the analysis since VDZ therapy has been stopped due to side effects. Mean duration of VDZ treatment in Crohn’s disease was 96.5±69.2 weeks and in UC was 72.1±60.5 weeks. Concomitant azathioprine therapy in CD increased VDZ persistence rate. However, in UC concomitant azathioprine therapy did not effect VDZ persistence rate.

Conclusion

The real-world data collected in this study demonstrate that concomitant azathioprine treatment increase the VDZ persistence rate in Crohn’s disease. However, concomitant azathioprine treatment does not effect the VDZ persistence rate in UC patients.
P428 Pharmacist led clinic in Inflammatory Bowel Disease
Authors: Kwok J , Smith J , Gashau W , Shuttleworth E
Published: January 2023

Background

Only 13% of IBD teams across the UK have a specialist pharmacist within the MDT (1). Pharmacists have a crucial role in safe and effective medication prescribing and monitoring (2). Studies have shown that pharmacist led clinics are acceptable to clinicians and patients (2). At our trust we set up a pharmacist led biologic switch clinic where a specialist pharmacist counselled regarding biologic therapy switch from intravenous (IV) to subcutaneous (SC) medication and assessed disease burden at baseline and follow up. We set up thiopurine clinic where the specialist pharmacist arranges monitoring and facilitates pre-emptive switch of stable patients to shared care prescribing with the GP, in line with the national commitment of providing convenient and easy access to services. We analysed patient feedback, biologic and shared care prescribing data to assess the impact of our pharmacist-led clinics.

Methods

Patients who had been scheduled in thiopurine and biologic switch clinic were sent with questionnaires either by post or email. Both paper and electronic data were collected and analysed using Microsoft ExCel. Biologic therapy and thiopurine prescribing and monitoring databases were setup and data were captured and analysed retrospectively.

Results

112 patients were switched from IV biologic therapy to SC therapy of which 8 patients needed to be switched back to IV due to either an adverse reaction or uncontrolled IBD. By reducing drug cost and increasing hospital CIU capacity, the biologic switch clinic has generated significant financial savings to the organisation (estimated £333,666 per annum).

In thiopurine clinic, 80 patients were identified as suitable candidates for shared care agreement with primary care. 88% patients have been successfully transferred to primary care and the remaining 12% remained under secondary care because the GP opted-out.

88% of patients who had been scheduled in pharmacist led clinic were happy with the service and the remainder had a neutral opinion regarding the service (see chart). Some patients fed-back that the telephone consultation did not happen at scheduled time or they preferred face to face clinic.

Conclusion

Pharmacist led clinic led to significant cost savings, increased accessibility to thiopurines and was acceptable to patients. In response to patient feedback we amended our appointment letters to clarify appointment time frames and give pharmacist contact details for further patient queries. We have also set up face to face clinics for patients preferring this option.

References:

1 Burns, Corrinne. Only 13% of IBD teams meet standards for pharmacist. London: Pharmaceutical journal, 2021

2 IBDUK. The hidden cost and a vision for change. London: Crohn's and Colitis care in the UK, 2021
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

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 (>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>T C/T variant was 13% (95% CI: 0.10-0.18), *3/*3 c.415C>T T/T variant was 2% (95% CI: 0.01-0.02), *1/*5 c.52G>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>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>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>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>T C/T variant and the *3/*3 c.415C>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

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 >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 >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

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

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 >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) >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 >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

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

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 > 26% male, >31% female), sarcopenia- assessed by hand-grip (defined as <30 kg male, <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<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

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

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 <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.
P468 Association of uncontrolled disease with quality of life and healthcare resource utilisation in Ulcerative Colitis patients treated with advanced therapy in the United States
Authors: Igho-Osagie E , Knight H , Barlow S , Harvey N , Khandker R
Published: January 2023

Background

Advanced therapies (AT; i.e., biologics, biosimilars, Janus kinase inhibitors) are used to treat patients with moderate to severe ulcerative colitis (UC) after inadequate response to conventional treatments; yet some patients continue to have uncontrolled disease. We examined the association between uncontrolled UC and health-related quality of life (HRQoL) and healthcare resource utilisation (HCRU) in a real-world clinical setting.

Methods

The analysis was conducted using secondary data from the Adelphi UC Disease Specific Programme™,1 a cross-sectional, retrospective survey of gastroenterologists and patients, from January 2020-March 2021. Gastroenterologists provided clinical characteristics and HCRU information for 5-7 consecutive UC patients, while EuroQol-5-dimensions (EQ-5D), EQ-visual analogue scale (EQ-VAS), short inflammatory bowel disease questionnaire (SIBDQ) and work productivity and impairment questionnaire (WPAI) were patient-administered to capture HRQoL status. Patients receiving AT for ≥6 weeks were classified as uncontrolled if: physician assessment was currently moderate or severe, they had ≥2 flares in the last 12 months, or currently had ≥3 symptoms. Patient characteristics and outcomes were compared using T-test and Fisher’s exact test. Multivariable linear regressions estimating the association between UC control status and HRQoL were adjusted for age, ethnicity, disease duration and severity at diagnosis.

Results

Of the 236 patients included in the sample, 57.6% had uncontrolled disease and were likely to be non-White (27.9% v 14.0% controlled; p=0.01). Although healthcare provider consultations were similar in both groups, uncontrolled patients had more radiological imaging (mean 1.9 v 1.3, p<0.01), endoscopies (mean 0.6 v 0.3, p<0.01) and hospitalisations (mean 0.2 v 0.1, p=0.01) in the last 12 months compared to controlled patients. Uncontrolled patients reported significantly lower (worse) total and subdomain SIBDQ scores (total: 47.2 v 59.6; systemic symptoms: 4.8 v 5.9; bowel symptoms: 4.7 v 6.1; emotional function: 4.6 v 5.6; social function: 4.8 v 6.2; all p<0.01; Table 3). EQ-5D (0.85 v 0.92, p<0.01), EQ-VAS scores (76.3 v 86.1, p<0.01) and activity impairment (29.2 v 16.7, p<0.01) were significantly worse in the uncontrolled group.

Conclusion

A substantial number of UC patients continue to have uncontrolled disease and high unmet need despite AT use. These patients experience poorer HRQoL and contribute a significant burden on healthcare resources. Study findings highlight the need for innovative therapeutic options that would further reduce disease burden for patients and the healthcare system.

1. Anderson P et al. Curr Med Res Opin 2008;24;3063–72.
P473 Corticosteroid-free clinical remission rates with guselkumab maintenance therapy in patients with moderately to severely active Crohn’s disease: Week 48 analyses from the phase 2 GALAXI 1 study
Authors: D’Haens G , Afzali A , Filip R , Rolim A , Terry N A , Salese L , Sahoo A , Frustaci M E , Yang Z , Andrews J M , Danese S , Hisamatsu T
Published: January 2023

Background

Corticosteroids are often used in Crohn’s disease (CD) to control inflammation. However, they are associated with adverse events; thus, achieving and maintaining remission without corticosteroids is a major treatment goal. GALAXI 1, a phase 2b, double-blind, placebo (PBO)-controlled study, evaluated efficacy and safety of guselkumab (GUS), a selective interleukin-23p19 subunit antagonist, in patients (pts) with moderately to severely active CD. Primary efficacy and safety data were presented previously. Here, we report corticosteroid-free clinical remission rates through Week (Wk) 48.

Methods

Pts with moderately to severely active CD were randomised in a treat-through design to GUS 200, 600, 1200mg; ustekinumab (UST) ~6mg/kg; or PBO intravenous (IV) induction followed by maintenance dosing (GUS 200mg IV-->GUS 100mg subcutaneous [SC] every 8 weeks [q8w], GUS 600mg IV-->GUS 200mg SC q4w, GUS 1200mg IV-->GUS 200mg SC q4w, UST ~6mg/kg IV-->UST 90mg SC q8w, PBO nonresponders-->UST ~6mg/kg IV-->UST 90mg SC q8w, PBO responders-->PBO SC q4w). Corticosteroid tapering was mandatory from Wk12 if medically feasible. Efficacy endpoints included corticosteroid-free CD Activity Index (CDAI) clinical remission (<150) and pt-reported outcome (PRO)-2 remission at Wk48 in the primary efficacy population. Pts randomised to PBO were not included in Wk48 efficacy analyses. GALAXI 1 was not powered to evaluate efficacy differences between treatment groups at Wk48; UST was a reference arm. Analyses were prespecified but not multiplicity controlled.

Results

At Wk48, 55.7-71.4% of pts in the GUS dose groups achieved corticosteroid-free CDAI clinical remission (Table 1). Similar rates were observed when the corticosteroid-free duration was ≥30 or ≥90 days before Wk48. Among pooled pts in CDAI clinical remission at Wk48 in the GUS groups, 115/120 (95.8%) were corticosteroid free. At Wk48, 49.2-68.3% of pts in the GUS dose groups achieved corticosteroid-free PRO-2 remission (Table 1). Among pooled pts in PRO-2 remission at Wk48 in the GUS groups, 105/110 (95.5%) were corticosteroid free. Outcomes in the reference UST group are shown in Table 1. Among pts in the GUS dose groups, 30.2-39.3% were using corticosteroids at Wk0 (median prednisone equivalent dose 20.0mg/d in each group); at Wk48, 60.0-78.9% of these pts met corticosteroid-free criteria (Table 2).

Conclusion

High rates of corticosteroid-free CDAI clinical and PRO-2 remission were achieved at Wk48 in the GUS dose groups. Among pts in clinical remission, most were corticosteroid free. Nearly all pts maintained corticosteroid-free CDAI clinical remission for ≥90 days. GUS IV induction followed by SC maintenance therapy also effectively reduced corticosteroid use at Wk48.
P500 Real life 2 year experience with ustekinumab in a Spanish open-label cohort of ulcerative colitis patients.
Authors: Iborra Colomino M I , Ferreiro-Iglesias R , Martín-Arranz M D , Mesonero-Gismero F , Mínguez A , Porto Silva S , García-Ramírez L , García de la Filia I , Bastida G , Nieto García L , Suárez Ferrer C , Aguas M , Barreiro de Acosta M , Nos P
Published: January 2023

Background

Ustekinumab has been recently approved for the treatment of moderately to severe ulcerative colitis (UC). Data from the UNIFI clinical trial are encouraging; nevertheless, real-world assessment is needed. We assess the effectiveness, safety and pharmacokinetics of ustekinumab in a cohort of refractory UC patients.

Methods

Multicentre and observational study of UC patients who received ustekinumab for active disease. Values for Partial Mayo Score (PMS), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8, 24 and 52 weeks and at 18 and 24 months when was possible. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalizations were documented. Possible predictors of response were examined.

Results

One hundred and eight patients were analyzed (Table 1).

Two patients only received the first IV dose. During follow-up, 58 patients (54%) required interval reduction (every 4 weeks (76%) and every 6 weeks (24%)) after a median of 22.3 weeks [11.6, 41.2]. Intravenous reinduction doses were administered to 20 (18.5%) after 27.7 weeks [6.64, 56.3]. Three patients required a maintenance therapy with IV administration. The clinical remission (PMS≤ 2) rates were 39.6%, 41%, 51% at 8, 24 and 52 weeks, respectively, and 61%, and 57.7% at 18 and 24 months, respectively. FC levels returned to normal (<250 μg/g) in the 39.6%, 41%, 51%, 61%, 58% of the patients at weeks 8, 24 and 52 and at 18 and 24 months respectively. CRP returned to normal (<3 mg/L) in the 79%, 75%, 76.5%, 71% and 70% of the patients at weeks 8, 24 and 52 and at 18 and 24 months respectively. PMS, FC and CRP values and ustekinumab through levels over time are shown in Figure.

Fewer previous anti-TNF agents and the loss of response to anti-TNF were associated with clinical response and with normalization of FC respectively. No variables at baseline (body mass index, serum albumin, and lymphocytes count) were associated with ustekinumab through levels. Of the 17 patients with endoscopy before and after treatment, 6 were in remission and 3 with mild activity. The AEs were recorded in 5 (4.6%) patients, 12 (11%) were hospitalized and 9 (8.3%) had surgery. A total of 23 patients (21%) discontinued ustekinumab over time, the persistence rates were 98%, 91%, 83% and 81% at 8, 24, 48 and 96 weeks respectively.

Conclusion

This is the first study to show the real-world long-term effectiveness, persistence, endoscopic improvement and safety of ustekinumab in a cohort of highly refractory UC patients. The clinical remission preceded the FC normalization. Ustekinumab through levels and their pharmacokinetic require further investigations.
P523 Quality, safety and equity of care outcomes for inflammatory bowel disease patients at four tertiary referral centres in Australia using a cloud based management system Crohn’s Colitis Care (CCCare): A real world observational study.
Authors: Cheema M , Narouz I , Pipicella J , Garden F , Lynch K , Andrews J , Ghaly S , Connor S
Published: January 2023

Background

Inflammatory bowel disease (IBD) is a global problem and Australia has amongst the highest prevalence rates. This study looked to assess the quality, safety and equity of care across four specialised IBD centres in Australia over a 12-month period using the cloud-based IBD clinical management system called Crohn’s Colitis Care (CCCare). This study aimed to define existing care at each centre and the range of performance across each centre to propose potential benchmarks for optimal quality IBD care.

Methods

The study was conducted across four tertiary IBD centres in Australia (Centres A, B, and C were public hospitals and D was a private centre). De-identified data within the backend CCCare research registry was audited between 1st of July 2021 to 31st August 2022. People with IBD who had a clinical assessment documented within the platform during this 12-month period were included.

We assessed quality of IBD care using disease activity based on patient reported outcome measures (PROMs), biomarkers and endoscopy; surgery rates; health maintenance indicators including vaccination and skin cancer screening rates and; key performance indicators including steroid use, smoking rates and current opioid use. Safety of care was assessed using adverse events from therapy and hospital admission due to therapeutic complications. Equity of care examined education levels and ethnicity.

Results

A total of 1889 patients were included. 63% had Crohn’s disease and 37% had ulcerative colitis. 51% of the cohort was female. The median age was 39 years (IQR 30-53) and the median disease duration was 8.4 years (IQR 3.3-15.7) (Table 1). Current steroid use was between 6% to 15.4%. Faecal calprotectin (FCP) remission rates (250μg/mg) were between 65-84% and patient reported outcome (PRO-2) remission rates were between 76-88% with the highest rates observed at Centre D (Figure 1). 74 patients underwent a surgical procedure. COVID-19 vaccination rates were between 40.1% to 88.8% with the highest rates once again observed at Centre D. 3% of the cohort was documented as currently using opioid medications. 12.2% were recorded as currently smoking at Centre A compared to 2.6% at Centre D. 55 medication related adverse events were recorded and 94 patients had a hospital admission during the study period.

Conclusion

This study showcases how CCCare can readily provide researchers with granular, real-world data to audit the quality of IBD care at 4 specialised centres in Australia over a 12-month period. While there were some differences (higher vaccination rates, lower smoking and steroid use rates at Centre D), quality and safety of care was still fairly uniform across the various sites and can serve as a standard of care for IBD patients in Australia.
P529 Year-two follow-up results of an observational study conducted in Crohn’s disease and ulcerative colitis patients treated with infliximab biosimilar CT-P13 in a real-life setting
Authors: Laharie D , Pierron G , Brault Y , Bouhnik Y , Nancey S
Published: January 2023

Background

ReFLECT study has been carried out to investigate real life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Aims: describe the profile of inflammatory bowel disease (IBD) patients (pts) treated with CT-P13 in a real-world setting and the treatment durability over time.

Methods

ReFLECT is a multicentre, prospective, observational study conducted in France. Eligible pts were IFX naive pts (IFX-N) starting CT-P13 and those who have been switched from infliximab originator to CT-P13 (IFX-S). Treatment maintenance was described indirectly and expressed as the percentage of pts without treatment failure during the 2 years of follow-up; treatment failure was defined as a permanent discontinuation of CT-P13 due to lack or loss of response and/or intolerance or death. Two years of follow-up final results of adult IBD pts using descriptive statistical analyses, are presented here.

Results

Among the 1400 adult pts included from Oct 2016 to April 2019, 751 had an IBD and 649 had a rheumatic disease; 530 pts with Crohn’s disease (CD; 51.5% females; mean age±SD: 38.1±13.9 years old; 327 IFX-N / 188 IFX-S) and 221 with ulcerative colitis (UC; 44.8% females; 43.5±17.3 years old; 152 IFX-N / 59 IFX-S), with a median disease duration since diagnosis of 7.5 and 6.2 years respectively. Nearly 80% of pts were already under CT-P13 before inclusion, and 35.3% of CD and 32.6% of UC pts had a concomitant treatment with AZA. At first CT-P13 administration, 54.3% of CD pts had an HBI>4 and 60.6% of UC pts had a Mayo score>6 in IFX-N pts compared with, 15.8% and 23.1% in IFX-S pts respectively. From first administration of CT-P13 to 24 months of follow-up, a higher proportion of pts without treatment failure was observed in IFX-S than in IFX-N pts: 83.7% [95%CI:78.0;89.9] vs 65.7% [58.6;73.7] in CD and 91.2% [81.7;100.0] vs 53.4% [43.0;66.2] in UC pts respectively (Figures 1 and 2). Main reason for CT-P13 withdrawing was treatment failure in IFX-N and IFX-S: 14.7% and 7.4% of CD, 21.7% and 5.1% of UC pts respectively. Withdrawing for intolerance involved 9.2% and 7.4% of CD, 7.2% and 3.4% of UC naive and switched pts respectively. Regarding safety (Table 1), 51.3% CD pts and 45.2% UC pts reported at least one adverse event (AE). AEs with suspected relationship with CT-P13 were described in 18.5% and 17.6% and serious AEs in 13.2% and 12.7% of CD and UC pts respectively. AEs were balanced between IFX-N and IFX-S.

Conclusion

2 year follow-up data indicate that CT-P13 induce effective therapeutic maintenance in pts with CD and UC receiving IFX for the first time, and maintain a sustained disease control in pts having switched from IFX originator to CT-P13. This real-life study did not highlight any new safety concerns.