bluuebunny/crossref_metadata_2025_split huggingface dataset:
P413 Withdrawal versus continuation of thiopurine in vedolizumab-treated patients with Ulcerative Colitis (VIEWS): a multi-centre randomised controlled trial
Authors: Pudipeddi A , Paramsothy S , Kariyawasam V , Paramsothy R , Ghaly S , Haifer C , An Y K , Begun J , Connor S , Corte C , Ward M , De Cruz P , Fung C , Redmond D , Leong R W 
Published: January 2023

Abstract

Background
The benefit of continuing thiopurine in ulcerative colitis (UC) responders to vedolizumab (VED) is unclear. We aimed to determine the effect of thiopurine withdrawal in VED-treated UC patients on combination therapy.

Methods
This prospective multi-centre, single-blind, randomised controlled trial recruited UC patients on VED 300mg IV every 8 weeks and a thiopurine for ≥6 months. Patients in steroid-free clinical remission (partial Mayo score[pMS]≤2, no subscore&gt;1) and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomised 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 VED trough levels. Secondary outcomes were disease relapse (pMS≥3 and faecal calprotectin&gt;150μg/g or increase in MES≥1 from baseline), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission, faecal calprotectin (remission&lt;150μg/g) and adverse events.

Results
Sixty-two consecutive patients (58% males, median follow-up 23.0 months) were randomised to withdraw (n=42) or continue (n=20) thiopurine. Randomisation was balanced. Complete data was available for 58 patients. There was a non-significant trend toward increased disease relapse in the withdrawal group (P=0.12, Fig. 1). In the withdrawal group, baseline histologic activity significantly increased disease relapse (HR:5.8, 95%CI:1.6-20.8, P=0.007, Fig. 2). There was a trend towards higher relapse rates in the withdrawal versus continue groups for bio-exposed patients (50.0% [6/12] vs 0.0% [0/4], P=0.07) but not bio-naïve patients (20.0% [6/30] vs 12.5% [2/16], P=0.52). At week 48, the continue group had significantly higher histologic remission (OR:4.6, 95%CI:1.1-18.9, P=0.03) and histo-endoscopic remission rates (OR:4.6, 95%CI:1.3-16.1, P=0.01, Fig. 3) versus the withdrawal group, but similar endoscopic remission rates (P=0.09, Fig. 3). Faecal calprotectin remission was significantly higher in the continue (94% [16/17]) versus withdrawal group (70% [28/40], P=0.047) with mean calprotectin 44.5μg/g±SD56.2 vs 209.6μg/g±SD344.2 (P=0.003) respectively. On multivariate analysis, histologic activity at baseline (HR:5.3, 95%CI:1.1-26.2,P=0.04) predicted disease relapse. Week 48 median VED levels were 15.9µg/mL (IQR:10.1-22.7) in the withdrawal group versus 14.7µg/mL (IQR:12.1-18.7) in the continue group (P=0.43). No patients had anti-VED antibodies. There was no significant difference in adverse events between groups.

Conclusion
Although thiopurine withdrawal did not affect VED trough level, it increased calprotectin, histologic and histo-endoscopic activity in UC. In patients with histological activity despite deep remission, thiopurine withdrawal significantly increased the risk of disease relapse.
P415 Real-world data in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional LISTEN II study
Authors: Stallmach A , Schulze H , Teich N , Cavlar T , Jana K , Henneberger S 
Published: January 2023

Abstract

Background
Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking integrin antibody and is approved for treating patients with moderately to severely active UC (ulcerative colitis) and CD (Crohn’s disease) intravenously (IV) or subcutaneously (SC). The LISTEN II study aims to determine patient characteristics and effectiveness in patients treated with VDZ in a real-world setting.

Methods
LISTEN II is a multicentre, prospective non-interventional study in Germany. Adult patients with UC or CD, for whom the physician has decided to either initiate VDZ IV or switch from IV to SC, are included. Data on patient characteristics, modalities of VDZ use and disease activity (pMayo, HBI) are followed up quarterly for up to one year per routine practice. In addition, patient reported outcomes (PROs) confirmed as relevant in the previous LISTEN I study (e.g. rectal bleeding and general wellbeing) are recorded via an app (ePRO).

Results
Data of 198 UC patients (50% female, 6.0 years median disease duration) and 116 CD patients (56% female, 10.9 years median disease duration) with a mean age of 40 years were included in this interim analysis. VDZ treatment was newly initiated IV in 164 UC patients and 98 CD patients (start) and switched from IV to SC by 34 UC and 18 CD patients (switch) at study inclusion. At baseline corticosteroids were documented as used in 70% and 56% of UC and CD start-patients in the year prior to enrollment.
Burden of disease was classified as high (pMayo&gt;4) in 51% of UC patients at baseline and decreased to 15% at 3 months. For CD patients, proportion of high burdened patients (HBI&gt;7) was 27% at baseline and 12% at month 3 (Figure 1). In this period, total mean pMayo score decreased in UC patients from 4.3±2.5 (start: 4.9±2.1; switch: 1.0±1.3) to 2.2±2.2 (start: 2.5±2.2; switch:1.0±1.6) and total mean HBI score from 5.4±4.4 (start: 5.8±4.5; switch: 3.5±3.7) to 3.3±3.4 (start: 3.4±3.4, switch: 2.8±3.3) in CD patients (Figure 2).
UC patients using the ePRO (N=152, mean age: 39 years, 49% female) reported from ePRO initiation up to month 3 a mean score decrease for rectal bleeding (range 0-3) from 1.3 to 0.6, for general well-being (range 0-4) from 1.7 to 1.3 and for impact on work productivity (range 0-10) from 3.7 to 2.3 points.

Conclusion
LISTEN II real-world data support the effectiveness of VDZ treatment in UC and CD patients. Patients starting VDZ IV showed a higher disease activity at baseline which decreased under VDZ treatment. Switching of VDZ IV to SC was mainly performed in patients with low disease burden under VDZ treatment, resulting in maintained therapeutic effectiveness. Also PROs of UC patients show an improvement supporting benefit with VDZ treatment.
P416 The impact of remission on healthcare resource utilisation and costs amongst patients with inflammatory bowel disease in France, Germany, Italy, Spain, and the United Kingdom
Authors: Patel K V , Salmon P , Marin-Jiménez I , Thessen M , Kligys K , Sharma D , Sanchez Gonzalez Y , Kershaw J 
Published: January 2023

Abstract

Background
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) with increasing healthcare resource utilisation (HCRU) and associated costs. Optimal management of CD and UC aims to induce and maintain remission which may subsequently lower HCRU and costs. This study reports on the potential impact on HCRU and associated direct HCRU costs (excluding drug costs) from achieving CD or UC remission in France, Germany, Italy, Spain and the United Kingdom (EU5).

Methods
Data were drawn from an Adelphi Real World IBD Disease Specific ProgrammeTM, a point in time survey collected from gastroenterologists and their IBD patients in EU5 in Sep 2020-Jan 2021. GEs completed a patient record form for their next 5-10 consulting IBD patients covering demographics, remission status, healthcare professional visits, tests used to diagnose and monitor CD/UC, hospitalisations and surgeries related to IBD. Patients were stratified into two groups based on GE stated remission status from set categories: remission (RE) vs non-remission (NR). Associated HCRU costs were sourced from published healthcare system reports per country. Outcomes and costs were compared between patients in RE vs NR using inverse probability weighted regression statistical analysis (α=0.05), adjusting for age, sex, BMI, smoking status, disease location, and current treatment.

Results
A total of 1,526 CD patients were analysed and split into patients in RE (n=1,021) and NR (n=505; Figure 1). Compared with CD patients in NR, patients in RE experienced a lower risk of at least one hospitalization (12.8% vs 29.8%; p&lt;0.001) and surgery (13.8% vs 26.0%; p&lt;0.0001) (Figure 2), and fewer visits to HCPs in the last 12 months (6.5 vs 7.4; p=0.005) (Figure 3). Furthermore, total HCRU cost was 53% less for patients in RE vs NR (€1410.4 vs €2153.4; p=0.0002), with 16% lower HCP visit and test costs (€637.1 vs €737.3; p&lt;0.001) and 83% lower hospitalisation and surgery costs (€773.3 vs €1416.2; p=0.001) (Figure 3). In addition, 1,447 UC patients were analysed and split into patients in RE (n=968) and NR (n=479; Figure 1). Compared to UC patients in NR, patients in RE experienced a lower risk of at least one hospitalization (11.4% vs 24.3%; p&lt;0.0001) and surgery (1.8% vs 5.0%; p=0.004 (Figure 1), and fewer HCP visits (6.0 vs 7.1; p&lt;0.001) (Figure 3). Total HCRU cost trended lower amongst patients in RE vs NR (€1219.6 vs €1443.0; p=0.085), with 19% lower costs of HCP visit and test costs (€617.3 vs €734.7; p&lt;0.0001).

Conclusion
Patients with IBD who achieve remission present lower HCRU burden, lower risk of hospital and surgery, and ultimately lower associated direct HCRU costs to healthcare systems in EU5.
P419 Outcomes at one year after sequential use of high-dose tofacitinib following infliximab in Acute Severe Ulcerative Colitis
Authors: Eqbal A , Hilley P , Gilmore R , Li Wai Suen C , Choy M , De Cruz P 
Published: January 2023

Abstract

Background
Acute Severe Ulcerative Colitis (ASUC) remains a significant cause of morbidity faced by up to 25% of patients with ulcerative colitis at some point during their disease course. We present the outcomes up to 1 year after the novel use of high dose tofacitinib, in patients with steroid refractory ASUC after failing to respond to infliximab.

Methods
Eleven patients with ASUC who were treated with high dose sequential tofacitinib [10mg three times daily (TDS)] after failing to respond to infliximab between 2019-2021 were identified at an Australian tertiary centre.

Results
Nine of 11 patients demonstrated a clinical and biochemical response to treatment during admission. All 9 patients remained colectomy free at both 6 and 12 months. At 6 months the median Mayo score was 1 [range 0-7]. At 12 months the median Mayo score was 1 [range 0-6]. No patients experienced venous thromboembolic events or major infective complications.

Conclusion
High dose tofacitinib may be a safe and effective agent in the treatment of steroid refractory ASUC after failing to respond to infliximab. Prospective studies are required to explore the use of tofacitinib in ASUC before it can be routinely recommended as salvage therapy.
P425 The utility of intestinal ultrasound to inform clinical decision making
Authors: Yeaman F , Panaccione R , Ma C , Lu C , Seow C , Kaplan G , Maracle B , Novak K 
Published: January 2023

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease leading to progressive bowel damage. Objective monitoring is essential to improve outcomes. Intestinal ultrasound (IUS) is an accurate, repeatable modality preferred by patients. The aim of this study was to evaluate changes in medical therapy and further tests requested, when IUS is used routinely to follow patients in an expert centre.

Methods
This is a single centre, prospective observational cohort study. All recruited provided informed consent with ethics approval through the University of Calgary. Patients over the age of 18 years were recruited via convenience sampling from October 1, 2020 to September 31, 2022. Patients were part of a registry where clinic-based IUS is standard of care. Patient demographics, medical treatment changes and further investigations were recorded.
IUS were performed by an IBD gastroenterologist trained in advanced IUS. Patients were classified as symptomatic (Harvey Bradshaw Index [HBI] ≥5) or asymptomatic (HBI&lt;5). IUS were categorised as inactive if the bowel wall thickness (BWT) was &lt;3mm without colour Doppler and inflammatory mesenteric fat) or active (BWT ≥3mm, colour Doppler ≥2 and presence of inflammatory fat). Data were reviewed regarding management: medication changes were defined as dose change, addition of corticosteroids or other medication and medication change. Referral for surgical opinion was recorded. Further outcomes included faecal calprotectin, stool for infection, blood tests, endoscopy, imaging or hospital admission.

Results
138 episodes of care were logged including 103(74%) with Crohn’s disease, 16(12%) with ulcerative colitis, 2(1.4%) with IBD-unclassified, 13(9.4%) without IBD investigated for symptoms and 4(2.9%) not recorded. Figure 1 shows symptomatic and active episodes compared to asymptomatic and inactive. IUS were performed: for flare symptoms in 22(16%); for monitoring in 107(78%); or to investigate symptoms in 9(6.5%). IBD medication was escalated in 22(52%) patients with active IUS disease plus symptoms and in 9(39%) asymptomatic patients with active IUS. Medication escalation was performed in 4(16%) symptomatic patients with inactive IUS and 2(4.2%) asymptomatic patients with inactive IUS based on low drug level or adverse events. One patient had medication reduced in frequency due to the IUS findings(Table 1). No hospital admissions occurred following IUS.

Conclusion
Active IUS triggered treatment modification in almost 40% of patients, regardless of symptoms. Future studies will assess benefits of timely treatment changes for long term outcome. IUS supports a clinician at the bedside to make timely clinical decisions that may avoid invasive testing and decrease resource limited endoscopy.
P431 A Pan-European Real-World Study of SB5 biosimilar following transition from reference adalimumab: The PROPER study; 48-week analysis of persistence
Authors: Dignass A , Gisbert J P , Bossa F , Kelly O , Rahman M , Lobatón T , Addison J 
Published: January 2023

Abstract

Background
SB5, a biosimilar to reference adalimumab (ADL) received marketing authorisation in 2017 (EU) and 2019 (US) based on pre-clinical and clinical phase I and III study data demonstrating bioequivalence and comparable efficacy, safety and immunogenicity to ADL. The real-world study “Pan-EU Real-World Experience with Imraldi” (PROPER) was designed to provide insights into outcomes, including predictors of persistence, following transition from ADL to SB5 outside the randomised, controlled trial setting.

Methods
Under an umbrella design, 1040 patients with immune-mediated inflammatory disease (rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], Crohn’s disease [CD] or ulcerative colitis [UC]) who had received at least 16 weeks of treatment with ADL prior to transition to SB5 were enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK and followed for 48 weeks post-transition. Candidate predictors of persistence on SB5 included sex, medical history, age, duration of disease, disease score and concomitant therapy, all as recorded at time of SB5 initiation. Variables of clinical relevance reported for at least 15% of each cohort were selected as candidate predictors and fitted into a univariate Cox regression model. Persistence on SB5, i.e., time to SB5 discontinuation up to Week 48 post-transition was estimated using the Kaplan-Meier method. This abstract presents results for the CD cohort.

Results
Of 447 CD patients included, 433 completed 48 weeks’ follow-up; 316 of those (70.7%) remained on SB5 throughout. The probability of persistence (95% Confidence Interval [CI]) at Week 48 was 71.8% (67%, 76%) (Figure 1).
Figure 1. Persistence on SB5

Table 1 shows the six variables qualifying as candidate predictors in the CD cohort and the probability of each to predict persistence at Week 48. Being female was the only variable shown to be associated with non-persistence of SB5: Hazard ratio (95% CI) 2.21 (1.54, 3.18). The 95% CIs of the other variables all crossed 1.0.
Table 1. Probability of candidate variable to predict persistence on SB5

Conclusion
The majority of the CD cohort remained on SB5 at 48 weeks after transition from reference ADL. Of the candidate predictors of persistence, only female sex was found to have an association with increased risk for SB5 discontinuation. A limitation of this finding is the low proportion of subjects discontinuing SB5 prior to Week 48, hence a low incidence of potential candidate predictors. When anticipating persistence, results suggest no evidence to mitigate against transition, within the baseline categories explored.
P432 Patient satisfaction and patient costs associated with telephone clinic appointments in Inflammatory Bowel Disease (IBD) following the pandemic
Authors: Matini L , Stokes E A , Parra Mujica F , Kormilitzin A , Kantschuster R , Punj Sharda A , Dunbar G , Song K , White L , Travis S P L , Walsh A 
Published: January 2023

Abstract

Background
Prior to the COVID-19 pandemic, conventional management of outpatient care in IBD predominantly revolved around face-to-face clinic appointments. In the changing landscape of care provision during the pandemic, appointments were conducted almost exclusively through telephone consultation. An electronic questionnaire was developed to assess patient satisfaction and patient costs.

Methods
A pilot was carried out with 15 patients to identify any technical issues with e-mail delivery of the questionnaire and gauge face validity of the questionnaire content. 1400 patients registered with the TrueColours-IBD remote digital monitoring system were sent the questionnaire link via e-mail in May 2021. No demographic data were collected by design, in order to avoid the perception of bias and ensure freedom of expression through anonymity.

Results
506 responses were received including 21 duplicates which were excluded, totalling 485 valid responses. 408/485 patients reported having a telephone appointment with the IBD service since March 2020, 484/485 reported having had a face-to-face appointment in the past. 348/408 (86%) were either ‘very satisfied’ or ‘somewhat satisfied’ with their most recent telephone consultation, while 22 (6%) were either ‘very dissatisfied’ or ‘somewhat dissatisfied’. 247/408 (61%) were also either ‘very satisfied’ or ‘somewhat satisfied’ with the ease of accessing further care if required, compared to 33/408 (8%) who were either ‘very dissatisfied’ or ‘somewhat dissatisfied’. Given the choice, 195/408 (48%) patients preferred to receive a telephone appointment in the future; 147/408 (36%) would opt for face-to-face and 66/408 (16%) stated no preference, all with the option of changing that choice if needed. Telephone appointments were associated with a mean total patient time off-work or leisure of 23 minutes (S.D. 51, n=408) compared to 190 minutes (S.D. 96, n=484) for face-to-face appointments. The average cost of time off work or leisure associated with telephone appointments was £5.55 (S.D. = £15.74, n=408), compared to £43.42 (S.D. = £31.27, n=484) for face-to-face appointments (Table 1). Costs of transport add further to face-to-face appointment costs. Greater proportions of patients had a companion for their face-to-face appointment and required childcare compared to telephone consultations (Table 2), which again increases the difference in costs.

Conclusion
Almost half of surveyed patients stated a preference for telephone appointments, although a third still preferred traditional follow-up. An evolution of care pathways is supported by patient preference and the statistically significant time and cost savings to patients receiving telephone appointments.
P438 Efficacy and safety of ustekinumab for Ulcerative Colitis through 4 years in Asian patients: Final results from the sub-population of UNIFI long-term extension
Authors: Hisamatsu T , Kim H J , Motoya S , Suzuki Y , Ohnishi Y , Marano C , Imai Y , Saadoun C , Zhuo J , Kawamura S ,   UNIFI Investigators
Published: January 2023

Abstract

Background
Ustekinumab (UST) is an interleukin-12/23 p40 antagonist approved for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the final efficacy and safety results of UST in the Asian subpopulation in the UNIFI long-term extension (LTE) through 4 years (Week [WK] 200).

Methods
Overall, 87 intravenous (IV) UST induction WK8 responders were randomised to subcutaneous (SC) maintenance therapy: 34 placebo (PBO); 24 UST 90 mg every 12 weeks (q12w); 29 UST 90 mg q8w. The nonrandomised patients (pts) included 22 IV UST induction nonresponders who received SC UST at WK8, responded at WK16, and continued on SC UST q8w; and 12 responders to IV PBO induction who received SC PBO.1,2 Pts who completed WK44 continued on SC UST q8w or PBO treatment in the LTE, and PBO pts were discontinued after unblinding. Starting at WK56, randomised pts with UC worsening could adjust to SC UST 90 mg q8w. Efficacy was evaluated in UST-randomised pts (n=53) using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0). Safety was evaluated for all pts treated in the LTE, including randomised and nonrandomised populations until WK220.

Results
Among all UST-randomised pts at maintenance baseline WK0 (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 49.1% were in symptomatic remission at WK200 (biologic naïve 77.8.%; failures 34.4%); 49.1% of pts were in corticosteroid-free symptomatic remission at WK200 (Table 1; Fig. 1-2). Overall, 43.5% of biologic failure and 0% of biologic naïve pts who were randomised to UST and treated in the LTE discontinued treatment between WK44 and WK200. Among randomised pts who continued UST in the LTE, 63.4% were in symptomatic remission at WK200; 78.6% of pts with observed data at WK200 were in symptomatic remission (Table 1; Fig. 3); and 80.0% of those in clinical remission at WK44 were in symptomatic remission at WK200. Safety events were similar among UST-treated pts compared with PBO. From maintenance baseline WK0 through WK220, pts receiving UST (combined UST) and PBO had 241.8 and 56.5 total pt-years of follow-up, respectively. Safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 222.48 vs 320.29, SAEs: 11.58 vs 7.08, and serious infections: 1.65 vs 1.77. During the final year of the LTE, no deaths or major cardiovascular events were reported in UST-treated Asian pts.

Conclusion
Consistent with the overall study population in UNIFI LTE1,2, Asian pts receiving SC UST generally maintained clinical benefit through 4 years. No new safety signals were observed.
1Afif W, et al. UEGW. Vienna, Austria, October 8-11, 2022. 2Sands BE, et al. ACG. Charlotte, NC, October 21-26, 2022