bluuebunny/crossref_metadata_2025_split huggingface dataset:
P414 Comparative real-world effectiveness and persistence of vedolizumab versus anti-TNF therapy in biologic-naïve patients with Crohn′s disease with propensity score adjustment: two-year maintenance phase results from the prospective VEDO-IBD study
Authors: Bokemeyer B , Plachta-Danielzik S , Efken P , Mohl W , Hoffstadt M , Krause T , Schweitzer A , Schnoy E , Atreya R , Teich N , Trentmann L , Ehehalt R , Franzenburg S , Hartmann P , di Giuseppe R , Schreiber S 
Published: January 2023

Abstract

Background
To gain insight into vedolizumab (VEDO) use as a first-line biologic in Crohn′s disease (CD), this comparative, two-arm prospective real-world-evidence (RWE) study with propensity score (PS) adjustment aimed to assess, within the maintenance phase, the 2-year comparative effectiveness and persistence of VEDO vs anti-TNF therapy in biologic-naïve CD patients.

Methods
Between 2017-2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD study from 45 IBD-experienced centres across Germany. 260 biologic-naïve CD patients starting a new therapy with VEDO or anti-TNF were included in this RWE comparison of VEDO vs anti-TNF. The Kaplan-Meier curve was used to summarize the treatment persistence from the start of therapy through week-104. The primary outcome was two-year clinical remission (HBI ≤ 4). Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI).

Results
63 VEDO and 197 anti-TNF (ADA: 58.4%, IFX: 41.6%) biologic-naïve CD-patients were evaluated. Two years after treatment initiation approximately 83% of VEDO patients were still in continuous treatment vs only 56% of anti-TNF patients (Fig. 1). In the mITT analysis (Fig. 2), there was a significantly higher clinical remission rate with VEDO when compared to anti-TNF after two years (VEDO: 64.2% vs anti-TNF: 44.7%), and a higher steroid-free remission (VEDO: 62.5% vs anti-TNF: 41.6%). Both differences were statistically significant (p&lt;0.05). Additionally (Fig. 3), using IPTW to examine the two-year maintenance effectiveness in week-14 induction phase responders, there was a significantly better response in terms of clinical remission for VEDO (88.6%) compared to anti-TNF (45.8%) (p=0.0001) and in steroid-free remission of 86.8% for VEDO compared to 44.1% for anti-TNF (p&lt;0.001).

Conclusion
Compared to previous RCTs, this prospective two-year RWE study comparing VEDO with anti-TNF showed that, in biologic-naïve CD patients, remission rates at two years with VEDO were remarkably higher than with anti-TNF. Given the favourable side effect profile of VEDO, these findings may aid physicians’ decision-making on the choice of VEDO as a first-line biologic for CD.
P436 Efficacy and safety of intravenous ustekinumab re-induction therapy in Crohn’s disease patients with secondary loss of response to ustekinumab maintenance therapy: Week 16 results from the POWER trial
Authors: Schreiber S W , Lee S , van der Woude C J , Marín-Jiménez I , Wolf D , Schnoy E , Salzberg B , Busse C , Nazar M , Langholff W , Borghorst S , Gasink C , Baker T , Godwin B , Feagan B ,   POWER Investigators
Published: January 2023

Abstract

Background
After successful induction, a subset of patients with Crohn’s disease (CD) experience a secondary loss of response (LoR) to ustekinumab (UST) maintenance therapy. Dose intensification may assist in regaining response. The phase 3b randomised, double-blind, multicentre POWER study evaluated efficacy and safety of a single intravenous (IV) re-induction UST dose vs continued UST subcutaneous (SC) treatment in CD patients with LoR to standard UST every 8 weeks (q8w) maintenance therapy.

Methods
Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and subsequently experienced LoR were included. LoR for inclusion was defined as CDAI score of ≥220 and ≤450, in addition to elevated CRP (&gt;3mg/L), fCal (&gt;250mg/kg) or endoscopy performed ≤3 months before W0 with evidence of active CD (≥1 ulcerations in the ileum and/or colon). At baseline (W0), randomised patients received either ~6mg/kg IV UST/SC placebo (IV arm), or IV placebo/SC UST 90mg (SC arm), followed by SC UST 90mg dosing in both groups at W8/16. Clinical and biomarker assessments were made at W0/8/16 and optional ileocolonoscopy at W0/16. Primary endpoint: clinical response (CRes; decrease of ≥100 points from W0/CDAI &lt;150) at W16. Additional outcome measures included clinical, biomarker, endoscopic and quality of life endpoints assessed at W8/16.

Results
The analysis set comprised 215 patients at W0 (IV, n=108; SC, n=107). At W16, 92.6% and 86.0% completed treatment from IV and SC arms, respectively. In both arms (IV, 58.3%; SC, 57.9%) most patients experienced ≥2 biologic failures before initiating UST (Table 1). At W16, 49.1% in the IV arm and 37.4% in the SC arm achieved CRes (p=0.089). Percentages of patients with normalisation of fCal, normalisation of CRP and/or fCal, endoscopic remission and improvement, and improvement in IBDQ score were greater in the IV vs SC arm (Table 2). At W16, similar proportions of patients had ≥1 adverse event (AE) (IV, 60.2%; SC, 61.7%) and serious AEs (IV, 5.6%; SC, 5.6%). The proportions of patients with infections were similar between arms (IV, 23.1%; SC, 21.5%), with only 1 serious infection in each arm.

Conclusion
POWER is the first randomised, controlled, double-blind trial to assess the efficacy and safety of UST IV re-induction in patients with LoR during UST maintenance therapy. The CDAI-based primary endpoint at W16 was not met. However, patients in this heavily pre-treated population who received IV re-induction showed clinically meaningful improvements at W16 compared with those receiving SC, particularly for objective endpoints, including inflammatory biomarkers and endoscopic outcomes.
P437 Early therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome
Authors: Carrillo Palau M , Alonso-Abreu I , Morant A , Vera B , Vela M , Ramos L , Franco A , Reygosa C , Barrios Y , Medina Chico J S , Globio V , Hernández-Perez A , Jiménez A , Hernández-Guerra M 
Published: January 2023

Abstract

Background
Anti-TNF drugs are effective treatments for the management of Inflammatory Bowel Disease (IBD), yet treatment failure is common. Monitoring drug levels and their antibodies (ATIs) can be useful to optimize the management of patients. In addition, the HLA-DQA1*05 gene has been recently related as a possible marker of immunogenicity and loss of response to anti-TNF therapy.The aim of this study was to evaluate the clinical impact of determining adalimumab (ADA) levels and anti-adalimumab ATIs in patients with IBD, and the influence of the HLA-DQA1*05 allele on the response and maintenance of adalimumab treatment in this population.

Methods
This observational, multicentric and prospective study enrolled patients who started treatment with ADA from October 2020 to October 2022. Demographic data and IBD characteristics were recorded. Clinical Activity Index (Harvey Index and Parcial Mayo Score) and C reactive protein(CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was used to assess the correlation between ADA levels and activity disease at different points

Results
We included 131 (age 42±17 years, 56% female) IBD patients (78% Crohn`s Disease, 21% Ulcerative Colitis and 1% Indeterminate colitis) who started treatment with ADA (80% were naïve to anti-TNF and 57% started ADA combined with immunomodulator treatment). At baseline, 81% had an active disease (Global Physician Assesment=1), 49% had CRP &gt;5 mg/L and 77% had FC &gt; 150 mg/kg. PRO at baseline was 63±9.1. HLA was determined in 99 patients, of whom 42 (42%) were HLA-DQA1*05 positives. We found a positive correlation between PRO score and Hb levels and albumin, meanwhile a negative correlation with FC and CRP at week 0. No correlation with ADA levels or ATIs was established. Patients HLA-DQA1*05 positive had not more adverse reaction or ATIs during the observational period. Patients with ADA serum concentration &gt;7µg/mL at week 4 had CRP &lt;5mg/dL at week 4 (p=0.04) and at week 10 (p=0.01). Patients with ADA serum concentration &gt;7µg/mL at week 10 had more stable disease (PGA =0) and CRP &lt;5mg/L, FC &lt;150 mg/kg at week 10 (p&lt;0.05), CRP &lt;5mg/L at week 30 (p&lt;0.05) and FC &lt;150 mg/kg at 12 months.

Conclusion
Early Drug level monitoring of Adalimumab (after induction) may improve the management of IBD patients. Our study shows that ADA levels &gt;7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.
P444 A systematic literature review (SLR) of real-world studies of advanced therapies in moderate-to-severe ulcerative colitis (UC): study, patient and clinical characteristics, and outcomes assessed
Authors: Irving P M , Hur P , Gautam R , Guo X , Vermeire S 
Published: January 2023

Abstract

Background
Variability in real-world (RW) study designs is often seen as a limitation for drawing conclusions. With more RW studies assessing effectiveness and safety of advanced therapies (ATs) in patients (pts) with moderate to severe UC, there is a need to better understand the study characteristics, clinical characteristics, treatments (Tx), and outcomes.

Methods
We conducted a SLR as per methodology described by Cochrane Collaboration and PRISMA guidelines, using Embase®, MEDLINE®, and MEDLINE®-In Process databases to find RW studies assessing biologics [bio] (adalimumab, golimumab, infliximab, vedolizumab/VEDO, and ustekinumab) or small molecules (filgotinib/FIL, ozanimod/OZA, and tofacitinib/TOFA) for adults with UC. Only products approved at the time of search were included. Studies published in English as full papers (Jan-2005–Feb-2022)or conference abstracts (Jan-2019–Feb-2022) were included. Studies with &lt;30 pts or with only bio-naïve pts were excluded.

Results
From 3930 search results, 139 studies were included. Of these, 75% were published between 2019–2022; 64% were retrospective observational; and 53% were from 5 countries (Italy, US, Spain, UK, and Belgium). The median age of pts across studies was 26–55 years and male proportion ranged 25%–73% (Fig 1). 13% of studies had only bio-exposed pts, 63% had &gt;50% pts bio-exposed and 28% presented sub-analysis for bio-exposed pts.
Most studies (87%) were single arm; VEDO (41%) was the most evaluated Tx, followed by TOFA (20%). No studies were found for FIL or OZA. Clinical remission (CR; 69%), clinical response (69%), and steroid-free CR (46%) were commonly reported outcomes, whereas histologic (6%) and sustained remission (4%), and patient-reported outcomes (PROs; 5%) were uncommon (Fig 2). In studies reporting CR, Partial Mayo Score (PMS) or Full Mayo Score ≤2 alone or combined with rectal bleeding and stool frequency subscore ≤1 were commonly used definitions, followed by PMS ≤1 and Simple Colitis Clinical Activity Index ≤2. Most studies assessed outcomes within 52 weeks (76%). Any adverse event (AE; 46%), colectomy (46%), withdrawal due to AE (37%), and infections (24%) were frequently reported safety events. Only up to 12% of studies reported data on MACE, malignancies and VTE.

Conclusion
More than half of RW studies in moderate to severe UC originated from five countries with VEDO and TOFA being the most frequently assessed ATs. Comparative studies were limited. Several definitions of CR were used to describe effectiveness, and few studies assessed PROs and effectiveness beyond 1 year. Inconsistent reporting of safety events was identified. Future research should consider these findings when designing a study.
P447 Early predictors of the need for surgery in patients with acute severe ulcerative colitis: results of the prospective, observational, international ESCP MASC study
Authors: Frasson M , Pinkney T , Gisbert J P , Rodriguez-Lago I , Blackwell S , Gecse K B , Buskens C J , Knowles C , Zmora O , Brookes M , Fiorino G , Nos P , Gallo G , Pata F , Verjee A , Leone S , Pellino G 
Published: January 2023

Abstract

Background
Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition, requiring immediate hospitalization. Delayed colectomy is associated with increased risk of post-operative complications. This study aimed to identify early predictors of failure to medical treatment and need for colectomy in patients with ASUC.

Methods
The Management of Acute Severe ulcerative Colitis (MASC) Audit was an international, prospective, observational, cohort study, in which data on consecutive patients hospitalised for ASUC at participating units over a minimum 6-month period in 2019-20 were collated. The need for surgery during the first 90 days after admission was the primary outcome of the study. Data on all consecutive patients admitted for ASUC at the participating units were prospectively entered in an online secure database. A multivariate regression logistic model was developed to identify early predictors of colectomy.
The study was developed by a multidisciplinary panel of collaborators, including gastroenterologists, surgeons, and patients, and it was discussed at the 5th IBD National Study Group of the ECCO. The study was led by the European Society of Coloproctology (https://tinyurl.com/vfwmahva).

Results
Out of 706 patients included in the database, data from 699 patients from 123 centres located in 32 different countries were included in the analysed (Figure 1).

Median age was 38 (IQR, 28-54) years; 265 (38%) patients had a previous admission for UC and 39 (6%) had undergone previous appendicectomy. At admission, 13% patients were on monotherapy with 5-ASA, 19% systemic steroids, and 19% biologic agents. Within 90 days after admission, 258 (37%) patients required surgery: 29.7% received second-line and 1.4% received third-line medical therapy. Overall mortality was 1%. Among those patients requiring surgery, postoperative morbidity was 36% (Table 1).

Being a current smoker (OR 2.6, 95%CI 1.2-6.0), previous appendicectomy (OR 6.3, 95%CI 2.1-20.0), previous admission for UC (OR 2.6, 95%CI 1.5-4.4), admission to a surgical unit (OR 9.8, 95%CI 4.3-22.5), type of pre-admission therapy and C-reactive protein levels on day 3 after admission (OR 1.01 per mg/L, 95%CI 1.00-1.01, ROC curve in Figure 2) were independent predictors of failed medical treatment.

Conclusion
Mortality for ASUC did not exceed 1% in this series. Patients who smoked or had previous appendicectomy were at increased risk of medical failure. These factors seem to challenge the current knowledge on UC course, and the findings merit further investigation. C-reactive protein on day 3 after admission was identified as a potential marker to predict the subsequent need for surgery.
P467 5-ASA is not superior to no-maintenance in patients with newly diagnosed Crohn’s disease - a nationwide cohort from the epi-IIRN
Authors: Atia O , Goren I , Sharar Fischler T , Loewenberg Weisband Y , Greenfeld S , Kariv R , Ledderman N , Matz E , Magen Rimon R , Dotan I , Turner D , Yanai H 
Published: January 2023

Abstract

Background
5-aminosalicylates (5-ASA) are widely used in Crohn's disease (CD) despite guidelines advising otherwise. In this nationwide study, we aimed to assess the outcomes of first-line 5-ASA-maintenance therapy (5-ASA-MT) compared with no-maintenance treatment (no-MT) in patients with newly diagnosed CD.

Methods
We utilized data from the epi-IIRN cohort, including all patients with CD diagnosed in Israel between 2005-2020. Outcomes included therapeutic failure, hospitalization, surgeries, steroid dependency, escalation to biologics, and 5-ASA-related adverse events. Propensity-score (PS) matching was utilized to compare outcomes in the 5-ASA-MT vs. no-MT groups.

Results
Of the 19,264 patients diagnosed with CD, 3,027 (16%) received first-line 5-ASA-MT and 5,583 (29%) received no-MT. Both strategies declined over the years; 5-ASA-MT from 21% in 2005 to 11% in 2019 (p&lt;0.001) and no-MT from 36% to 23% (p&lt;0.001). The probability of maintaining therapy at one, three, and five years from diagnosis: 5-ASA-MT- 78%, 57%, and 47%, no-MT- 76%, 49%, and 38%, respectively (both p&lt;0.001). PS analysis successfully matched 1,993 pairs of treated and untreated patients and demonstrated comparable outcomes of time to: biologic (p=0.2), steroid-dependency (p=0.9), hospitalization (p=0.5), and CD-related surgery (p=0.1). On the other hand, rates of acute kidney injury (5.2% vs. 3.3%; p&lt;0.001) and pancreatitis (2.4% vs. 1.8%; p=0.03) were higher in the 5-ASA-MT group.

Conclusion
First-line 5-ASA-monotherapy was not superior to no-MT but associated with a slightly higher rate of adverse events, while both strategies have declined over the years. These findings suggest that a subset of patients with mild CD may be offered a watchful waiting approach.
P484 Inflammatory Bowel Disease exercise and diet habits (IBDeat) study: chronic metabolic disease risk factors among IBD patients in New Zealand
Authors: Yap J , Wall C , Meredith-Jones K , Iosua E , Osborne H , Schultz M 
Published: January 2023

Abstract

Background
Recent literature shows that patients with inflammatory bowel disease (IBD) are at higher risk of developing chronic metabolic diseases which may be amenable to a healthy lifestyle. However, this may be challenging for IBD patients as disease symptoms may result in unfavourable lifestyle habits such as avoidance of healthy foods and reduced physical activity. In this study, we aim to describe the nutritional status and lifestyle habits of adults with IBD in New Zealand (NZ).

Methods
A cross-sectional nationwide study was undertaken from December 2021 to October 2022 in NZ. Participants were recruited through social media and the Dunedin public hospital patient database. An online questionnaire collected demographics, disease severity scores (harvey-bradshaw index and simple clinical colitis activity index), quality of life (QoL), physical activity, and dietary intake data. A subset of patients living in Dunedin had anthropometrics, handgrip strength, blood pressure, body composition (bioelectrical impedance), blood nutritional markers (lipid profile, iron studies, vitamin D, vitamin B12, folate) and faecal calprotectin measured. Descriptive analysis was conducted and data were compared to population reference values. The study received University of Otago, Dunedin, NZ ethical approval (reference: H21/135).

Results
The questionnaire was completed by 197 adults, median age 37 (IQR 25, 51) of which 72% were female and predominantly NZ European ethnicity (82.4%). In this IBD cohort, 54% had Crohn’s disease and 46% had ulcerative colitis or IBD-unspecified with quiescent-mild disease activity. Two-thirds of patients had at least one comorbidity aside from IBD and one-third of patients had impaired QoL (defined by a score &lt;45). Most patients had nutritional risk factors including low intakes of fruits (91.3%), vegetables (94.4%), fibre (38.3%), and excessive intakes of fat (73.2%) and saturated fat (98.0%). Two-thirds of patients reported IBD-related barriers to exercise mainly due to fatigue (53.9%), abdominal pain (25.7%), bowel incontinence (23.3%), and joint pain (22.3%) in which only 59.7% met national physical activity recommendations. The Dunedin cohort (n=102) had further chronic metabolic disease risk factors such as central adiposity (63.7%), high body fat percentage (43.9%), high cholesterol/HDL ratio (29.3%), high blood pressure (26.5%), and poor handgrip strength (43.9%).

Conclusion
Findings suggest that NZ adults with IBD have multiple risk factors for chronic metabolic diseases that could be amendable to lifestyle interventions. Future studies should explore the feasibility and efficacy of nutrition and exercise lifestyle interventions to mitigate these risk factors.
P485 An Assessment Of A Guided Self-Help and Patient Initiated Review Pathway for Ulcerative Proctitis
Authors: Saunders J , Maroo S , Brownson E , Boulton Jones R 
Published: January 2023

Abstract

Background
The COVID-19 pandemic has placed great strain on standard outpatient services including those with IBD. There has been interest in using guided self-management and patient-initiated review to allow patients to manage their condition, while at the same time reserving outpatient capacity for those needing seen urgently. We developed a pathway for patients with stable ulcerative proctitis, which included a leaflet on symptom managment and when to contact the IBD nurses if ongoing symptoms.

Methods
Patients were identified from clinic lists cancelled during the pandemic who had a diagnosis of ulcerative proctitis. Case notes were reviewed to ensure a correct diagnosis and inclusion criteria met(stable disease,no immunosuppressant treatment). These patients were sent a Guided Self-Management leaflet in the post. A follow on questionnaire was sent 6 months after ensuring patients were happy with the information received. Non-responders were sent a second questionnaire and/or telephone call.

Results
37 Patients were identified. We received responses (via post, phone or email) from 28/37 patients (76%). 10/28 (36%) didn’t receive or do not recall receiving the leaflet. 18/28 (64%) received the leaflet. Of those who received the leaflet, 16/18 felt it was easy to understand and contained enough information to confidently manage their symptoms. 2 patients had 1 flare and 3 patients had multiple flares after receiving the leaflet. Of those with flares, 2 patients were able to self-manage their proctitis using the guided self help information. 2 patients had to contact the IBD nurses. These patients were called back within 24 hours and received useful advice. One patient had forgotten to use the leaflet. No one required rescue steroids or admission to hospital.
Overall, 17/18 (94%) felt the service was good or excellent compared to previous clinic review systems.

Conclusion
These results suggest patients are receptive to using guided self-management and patient-initiated review. Although we were not expecting to see many flares, given the low risk selected group, the results suggest patients can successfully manage flares and contact our services for support if required. It is a concern a significant proportion of patients did not recall receiving the leaflet.
Although this is a small subgroup, the results show clinic time can be saved which remains a pressurised resource as we recover from the pandemic. The principles of guided self management and patient initiated review could be applied to other patient groups(eg stable UC patients not on immunosuppressants). In future it would be important to ensure patients receive and understand the leaflet. A clinic appointment prior to discharge into such pathways should be considered.