bluuebunny/crossref_metadata_2025_split huggingface dataset:
P784 Real-world use and 6-month effectiveness of vedolizumab subcutaneous in IBD patients: results of the VEDO-IBD study
Authors: Plachta-Danielzik S , Bokemeyer B , Efken P , Mohl W , Hoffstadt M , Krause T , Schweitzer A , Schnoy E , Ehehalt R , Trentmann L , Teich N , Atreya R , Franzenburg S , Hartmann P , Wenske T , Schreiber S 
Published: January 2023

Abstract

Background
Since April 2020, vedolizumab (VEDO) has been available for use in IBD in intravenous (iv) and subcutaneous (sc) formulations. Due to limited data on real-world use and effectiveness, the objectives of this real-world evidence (RWE), observational, prospective study are to observe (1) the time point of conversion to VEDO sc, (2) the 6-month remission rate with VEDO sc. using data from the VEDOIBD study.

Methods
Between 2017-2020, 1200 consecutively enrolled patients with ulcerative colitis (UC) and Crohn’s disease (CD) were prospectively included in the VEDOIBD study from 45 IBD-experienced centers across Germany. Additionally, 74 VEDO-naïve patients were included with the goal of conversion to VEDO sc after an iv-induction period with VEDO (VEDO iv week 0, 2, 6). Effectiveness was measured by clinical remission (HBI ≤ 4) at month 6.

Results
A total of 180 IBD patients with a running VEDO iv therapy were converted to VEDO sc during the entire study, with at least one 6-month visit from 119 patients (UC: n=67; CD: n=52). Characteristics are shown in Table 1. 87 IBD patients (73.1%) were still receiving VEDO sc after 6 months. 32 IBD patients (26.9%) stopped VEDO sc therapy within the first 6 months. The majority of patients returned to treatment with VEDO iv (37.9%) and the others switched to other biologics: 24.1% ustekinumab, 34.5% anti-TNF (Figure 1). At the time of conversion to sc, 92 patients (77.3%) were in remission (UC: 75%; CD: 84.6%). Of those, 88% remained in remission at 6 months (UC: 89.6%; CD: 86.4%). 45.8% of patients not in remission at the time of conversion to VEDO sc were in remission at 6 months (UC: 50%; CD: 37.5%). Of the 74 patients with planned conversion to VEDO sc, 52 patients (70.3%) received VEDO sc as planned previously: 11.5% within the first 2 weeks, 42.3% after week 6, 19.2% after week 14, and 26.8% after six months or later.

Conclusion
IBD patients with a conversion from VEDO iv to VEDO sc show high effectiveness after 6 months; conversion usually was carried out between 6 and 14 weeks. Based on these data, VEDO sc is shown to be an effective alternative to VEDO iv in RWE and should therefore be considered an important option in treatment planning and discussion with patients.
P785 A retrospective cohort study on vedolizumab trough levels in Crohn’s disease patients
Authors: Pokryszka J , Stadlmann M , Primas C , Gerold N , Reinisch S , Novacek G , Reinisch W 
Published: January 2023

Abstract

Background
Background: Vedolizumab (VDZ), an α47-integrin inhibitor, is approved for the treatment of moderate to severe Crohn’s disease (CD). Exposure-response relationship for VDZ is less evident in CD. Here, we are exploring associations between serum VDZ serum concentrations and clinical/biomarker-defined endpoints from a single center, real-world cohort.

Methods
Methods: Electronic health data records of CD patients during their first year of treatment with VDZ from January 2014 – July 2022 at our tertiary care center were obtained. Serum drug levels (TDL) and their correlation with outcomes were assessed at specified timepoints – weeks 12 (± 2), 26 (± 4) and 52 (± 6). Clinical remission was assessed by patient reported outcomes as suggested in STRIDE II guidelines (stool frequency ≤ 3 and abdominal pain ≤ 1). Fecal calprotectin (fCP) values ≤ 150 µg/g marked biomarker remission. Vedolizumab drug levels were measured with IDKmonitor Vedolizumab drug level ELISA kit (Immundiagnostik AG, Germany), In case of missing data patients were categorized as non-responders. For association modelling, multivariable fractional polynomials and generalised additive models were used (R statistical software, v4.1.2; R Core Team).

Results
Results: In total, 58 patients (females = 55.2%) with at least two available data points were included (Table 1). Sixteen individuals (16/58, 27.6%) were naive for biologics therapies. 98.3% (57/58) reached week 12 (± 2). Both at weeks 26 and 52 91.4% (53/58) subjects still were on drug. Clinical remission was achieved in 51.7% (30/58), 49.1% (26/53) and 45.2% (24/53) cases at weeks 12, 26 and 52, respectively, with biomarker remission rates of 24.1% (14/58), 35.8% (19/53) and 27.6% (16/53) patients reached biomarker remission. TDLs differed only between clinical remitters and non-remitters at week 26 (Mann-Whitney-U-test, p = 0.04). Also, there was no significant association between clinical and biomarker remission at defined timepoints and corresponding TDLs (for all p &gt; 0.05). TDLs at week 2 and 6 were correlated with fCP values at the same time (rho: -0.327, p = 0.03 at week 2 and rho: -0.356, p = 0.02 at week 6). When TDLs at week 2 and week 6 were taken into consideration and associated separately with therapy outcomes in a univariate regression, only association between serum levels at week 6 and biomarker remission at weeks 26 and 52 was found (p = 0.02 and p = 0.03, respectively).

Conclusion
Conclusion: The only association between serum drug levels and remission was found between TDLs at week 6 and biomarker remission at weeks 26 and 52 suggesting a complex exposure-response relation for vedolizumab in CD patients.
P787 Subcutaneous infliximab in IBD patients with previous immunogenic failure of intravenous infliximab
Authors: Husman J , Matthes K , Gilger M , Arsova M , Schmidt A , Hampe J , Zeißig S , Schmelz R 
Published: January 2023

Abstract

Background
The immunogenicity of infliximab (IFX) is a major reason for secondary loss of response to intravenous (IV) IFX treatment. A lower incidence of anti-drug antibodies (ADA) with subcutaneous (SC) IFX treatment compared to IFX IV has been described1,2. Furthermore, data on four patients with immunogenic failure or allergic reactions to IFX IV documented safety of exposure to IFX SC3. Here, we analyzed the efficacy and safety of IFX SC in IBD patients with previous immunogenic/allergic failure to IFX IV in a monocentric analysis conducted at the Dresden University Hospital.

Methods
Immunogenic failure was defined as presence of ADA and low/undetectable IFX trough levels during IFX IV therapy. Patients received IFX SC 120 mg every other week (EOW). HBI and partial Mayo, IFX trough levels, free ADA, and fecal calprotectin (FCP) were determined at wk 0 and wk 12. Clinical remission was defined as HBI&lt;5 or partial Mayo≤1. FCP&lt;250ug/g was considered biochemical remission.

Results
Ten patients (7/10 with active IBD and 3/10 in remission) were included. All patients had previously developed ADA during IFX IV treatment. Two patients had suffered an IFX infusion-related allergic reaction. Baseline demographic parameters are shown in table 1. Patients were extensively pretreated (5/10 had previous treatment with ≥3 biologics). 5/10 patients were switched from ongoing IV application to IFX SC, while 5/10 were started on IFX SC without IFX IV induction. During follow up, 6/10 patients did not reach IFX trough levels≥3ug/ml, of whom four patients showed detectable ADA. 2/10 patients developed mild injection site reactions. No severe immediate hypersensitivity reactions were observed. Treatment persistence across wk 12 was 70% (7/10), while 3/10 patients discontinued IFX SC due to lack of efficacy. In the active IBD group, clinical remission at wk 12 was achieved in 1/7 patients. 2/7 patients showed a decrease in FCP from baseline to wk 12. Among the three patients who entered the study in remission, all maintained clinical and biochemical remission until wk 12 (3/3).

Conclusion
In this cohort, exposure of patients with previous immunogenic/allergic failure of IFX IV was well tolerated and safe. However, only a minority of patients established significant IFX through levels with EOW IFX SC therapy and clinical responses were heterogeneous. Further studies are required to assess the safety and efficacy of IFX SC in patients with previous immunogenic IFX failure and to investigate the value of dose intensification and/or interval shortening of IFX SC in this patient population.
References:
1 Smith et al, J Crohn Colitis, 2022
2 Schreiber et al, Gastroenterol, 2021
3 Caron et al, Aliment Pharmacol Ther, 2022
P793 Infliximab and prevention of colectomy in acute severe ulcerative colitis: an individual patient data meta-analysis
Authors: Wang Z , Afif W , Hanžel J , Kobayashi T , Papamichail K , Roblin X , Peyrin-Biroulet L , Vermeire S , Dreesen E 
Published: January 2023

Abstract

Background
Infliximab (IFX) is used to treat patients with acute severe ulcerative colitis (ASUC) who fail to respond to intravenous corticosteroid therapy. Yet, a significant proportion of patients does not respond adequately and requires colectomy. Our aim was to explore baseline predictors of colectomy-free survival during IFX rescue therapy in patients with steroid-refractory ASUC.

Methods
We performed an individual patient data meta-analysis (IPDMA) with data retrospectively collected from hospitalised, corticosteroid-refractory patients diagnosed with ASUC (based on Truelove and Witts’ criteria) who received IFX rescue therapy. Baseline characteristics including sex, smoking status, disease extent, disease duration, Mayo endoscopic subscore, serum albumin, C-reactive protein, haemoglobin, and white blood count were evaluated as predictors of colectomy-free survival at three and twelve months after start of IFX therapy. Data were analysed using R software (v4.2.0).

Results
Data were collected from six centres contributing a total of 140 patients (Table 1). Fifteen patients (10.7%) required colectomy within three months and another eight patients underwent colectomy by one year (total colectomy rate after one year 16.4%) (Figure 1). No baseline predictors of colectomy-free survival were identified (log-rank P&gt;0.05). Patients who received intensified IFX induction therapy (n=64, &gt;5 mg/kg), in contrast to patients on regular induction doses of 5 mg/kg at weeks 0-2-6 (n=49), did not have lower rates of colectomy.
A total of 53 IFX serum trough concentrations (TC) were measured in 31 patients. The median IFX TC during weeks (w)1-2 of therapy was 13.5 mg/L (interquartile range [IQR] 9.3-16.3 mg/L), and 7.0 (IQR 1.9-12.0) mg/L during w3-6. Target attainment rates were 8.3% (1/12 patients) and 18.2% (2/11 patients), respectively, towards the previously reported IFX TC targets of 28.3 mg/L at w2 and 15.0 mg/L at w6 for achieving endoscopic remission at w12.1 IFX TCs during induction were not significantly different between patients who received standard and intensified induction therapy.

Conclusion
Colectomy rates remain a significant burden of ASUC even for patients receiving IFX. In our interim IPDMA, we did not identify baseline predictors of colectomy-free survival. Poor target attainments of the previously established concentration targets demand dose optimisation. Pharmacometrics modelling of the IFX dose-exposure-biomarker/measure-response relationship within the spECTRUM consortium (DEFINE study) will facilitate dose-finding simulations to demonstrate the value of model-informed therapeutic drug monitoring.
References:
1. Papamichael et al. Clin Gastroenterol Hepatol. 2016.
P800 Upadacitinib is effective and safe for Crohn’s Disease: prospective real-world experience
Authors: Friedberg S , Choi D , Hunold T , Choi N K , Garcia N M , Picker E A , Cohen N A , Cohen R D , Dalal S R , Pekow J , Sakuraba A , Cleveland N K , Rubin D T 
Published: January 2023

Abstract

Background
Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report our prospective real-world experience with upadacitinib in patients with CD.

Methods
We performed a prospective analysis of clinical outcomes during upa therapy in patients with CD using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment evaluation protocol at our institution. We used the Harvey Bradshaw Index (HBI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as HBI ≥5. Clinical response was defined as a decrease of ≥ 3 points from baseline HBI. Clinical remission was defined as HBI &lt;5. Corticosteroid free clinical remission (CSFR) was defined as those in clinical remission, not taking any form of systemic corticosteroid at the specific time point. CRP normalization was defined as baseline elevated and then within the normal range for the lab used (Quest Diagnostics (Secaucus, NewJersey) ≤8 mg/L or University of Chicago Medicine ≤5 mg/L). FCP response and remission was assessed at three different cutoffs: less than 250 μg/g, 150 μg/g, and 50μg/g. Adverse events were recorded as treatment-related adverse events (AE) and serious adverse events (SAE).

Results
47 patients with CD received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 93.6% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At weeks 4 and 8, 16/21 (76.2%) and 12/16 (75.0%) achieved clinical response and 14/21 (66.7%) and 11/16 (68.8%) achieved clinical remission by 8 weeks, respectively (Table 2). Of those who were on steroids at baseline, 100% (5/5) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 52.6%. Mean HBI decreased from 6.7 (SD 4.6) at week 0 to 3.5 (3.7) at week 8 (Figure 1). Mean FCP decreased by 707.0 (SD 1026.0) μg/g at week 0 to 74.6 (SD 56.2) μg/g at week 8. Of those with FCP &gt;150 μg/g at baseline, 100% (4/4) achieved FCP &lt;150 μg/g by week 8 (Table 2). Mean CRP decreased by 12.8 (SD 19.1) mg/L to 4.9 (SD 8.0) mg/L at week 8. Of those with CRP &gt;5 mg/L at week 0, 80% (4/5) achieved CRP &lt;5 mg/L by week 8 (Table 2). 23.4% of patients had an AE after starting upa (Table 3). The most common of these was acne (14.9%). Two AEs led to discontinuation and there was a single possible SAE (anemia which was also multifactorial from severely active Crohn’s ileitis and vitamin B12 deficiency).

Conclusion
In this large, prospective real-world experience in medically-resistant patients with CD, we describe that upadacitinib is rapidly effective and safe.
P807 Pregnancy and maternal outcomes in a cohort of patients with Inflammatory bowel disease: Encouraging data from a multi-disciplinary clinic in a tertiary center
Authors: Avni Biron I , Hayat L , Ollech J E , Banai-Eran H , Narkis B , Houri O , Pauker M H , Shay V , Dotan I , Hadar E , Yanai H 
Published: January 2023

Abstract

Background
Pregnant women with inflammatory bowel diseases (IBD) are prone to adverse pregnancy outcomes. This study aimed to assess pregnancy outcomes and disease management for pregnant patients with IBD treated at a multi-disciplinary IBD- maternal-fetal medicine (MFM) clinic.

Methods
This retrospective cohort study included consecutive pregnant patients with IBD having a singleton gestation who attended the IBD-MFM clinic at the Rabin Medical Center between 2012 and 2019. We assessed disease activity and flare management at conception and through pregnancy for the IBD cohort. Pregnancy outcomes of interest included: adverse neonatal and obstetrical outcome and mode of delivery. We also assessed three integrative outcomes: a favorable and a poor pregnancy outcome and an unfavorable maternal outcome. The IBD pregnant cohort was compared with a cohort of non-IBD pregnant women who gave birth at the same shift (1:5-10 control). Multivariable logistic regression was used for risk assessment.

Results
141 IBD pregnant patients and 1119 non-IBD pregnant women were included. Mean maternal age 32[±4] years. IBD patients had a higher rate of nulliparity (70% [50/141] vs. 30% [340/1119], p&lt;0.001) and had a lower BMI (21.42 kg/m2 [19.18-23.44] vs. 22.48 [20.31-25.59], p=0.002). All other baseline characteristics were comparable. Among the IBD patients, 60% (85/141) were diagnosed with Crohn’s disease (CD), and the rest with ulcerative colitis (UC). At conception, 88% (124/141) were in clinical remission, 83% (117/141) were on maintenance therapy, and 30.5% (43/141) were on biologics. Through pregnancy, 36.2% (51/141) flared, 14% (20/141) received systemic steroids, and 3% (2/141) initiated a new biologic. Flares were significantly more frequent among patients with UC vs. CD (48.2%, [27/56] vs. 28.2%, [24/85], p=0.015). The majority of neonatal and obstetrical outcomes and all three composite outcomes were comparable between the IBD pregnant and the non-IBD cohorts, table 1. Cesarean delivery was more frequent among the IBD pregnant patients compared with the non-IBD pregnant women (34.8%, [49/141] vs. 24.1%, [270/141], p=0.021). Risk analysis revealed that a diagnosis of IBD was not associated with either a favorable or a poor pregnancy outcome, nor an unfavorable maternal outcome, see table 2.

Conclusion
In this IBD-pregnant cohort followed at a multi-disciplinary IBD- MFM clinic, outcomes were encouraging and comparable with the non-IBD cohort. A diagnosis of IBD was not associated with pregnancy or maternal outcomes.
P813 A scoping review on the assessment and improvement of health-related physical fitness in patients with Inflammatory Bowel Disease
Authors: Demers K , Bak M T J , Bongers B C , de Vries A C , Jonkers D M A E , Pierik M J , Stassen L P S 
Published: January 2023

Abstract

Background
Reaching the STRIDE-II therapeutic targets for inflammatory bowel disease (IBD) requires an interdisciplinary approach. Lifestyle interventions focusing on enhancing and preserving health-related physical fitness (HRPF) may aid in improving subjective health, decreasing disability, or even controlling inflammation. However, ambiguity remains about the status and impact of HRPF (body composition, cardiorespiratory fitness [CRF], muscular strength [MS], muscular endurance [ME], and flexibility) in IBD patients, hindering the development of physical activity and exercise guidelines. The aim of this scoping review was to provide an overview of the literature assessing HRPF components of interest (i.e., CRF, MS, ME, and flexibility) in IBD patients, as well as how HRPF is affected by physical activity and physical exercise training interventions.

Methods
A systematic search was performed in multiple databases up to 5 Nov 2022. Eligible studies included IBD patients and assessed HRPF components of interest or evaluated physical activity or physical exercise training interventions.

Results
The search yielded 7323 articles, of which 68 were included (Figure 1), with a median sample size of 42 (IQR 24–77). Of these studies, 53 were conducted in adults and 15 in children or adolescents. Most studies (n=32) focused on patients with Crohn's disease (CD), followed by studies that included both CD and ulcerative colitis (UC) patients (n=30) and studies that included only UC patients (n=6). A total of 56 studies assessed HRPF components, including CRF, MS, and ME (n=2); CRF and MS (n=5); MS and ME (n=7); CRF (n=13); MS (n=28); and ME (n=1) (Figure 2). Great heterogeneity existed in assessment methods, with frequent use of non-validated field tests (Table 1). According to limited studies that used gold-standard tests, CRF appears to be reduced in IBD patients, but controversial findings emerged regarding MS and ME. Physical activity or physical exercise training interventions in patients with IBD were evaluated in 22 studies, with only ten reporting effects on HRPF, overall indicating a favorable impact. However, most studies included only patients in remission or with mild disease activity, lacked proper patient selection based on HRPF, and the type and intensity of interventions varied across studies.

Conclusion
This review highlights a lack of literature on the accurate assessment of HRPF in patients with IBD, leading to a scarcity of evidence on the effect of physical activity and physical exercise training interventions. Future research should focus on validating practical field tests, elucidating the association between HRPF and patient-reported and clinical outcomes, and determining the optimal physical training paradigm for IBD patients.
P816 The efficacy of an over the counter multivitamin and mineral supplement to prevent opportunistic infections in patients with inflammatory bowel disease in remission
Authors: Laheij R , van Knippenberg Y , Heil A , Mannaerts B , Bruin K , Lutgens M , Sikkema M , de Wit U , Laheij R 
Published: January 2023

Abstract

Background
Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biological therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections.

Methods
Single-centre, randomized, double-blinded, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (vitamin group) versus identical in appearance placebo (placebo group). Patients with Crohn’s disease or ulcerative colitis using immunomodulators and/or biological therapy without vitamin deficiency were considered for participation in our study.
Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24 weeks period of follow up. The primary endpoint of this study was the difference in incidence of infection between the two groups measured by a validated questionnaire, the revised version of the ID screen to assess infection13.
Randomization was conducted by using computer generated random numbers with an allocation ratio of 1:1 to vitamin supplement or placebo in blocks of 8 and stratified according to type of IBD.Results
Between July 2020 and February 2021, 320 patients were randomized. Treatment arms consisted out of 162 and 158 for vitamin and placebo, respectively. Both groups showed similarity in patient characteristics. All patients were included in the intention-to -Treat (ITT), 265 patients in the per protocol (PP) (compliance &gt;80%) analyses. For both groups, 107 patients reported an infection during the 24 weeks follow up period (Unadjusted Odds Ratio: 0.93 (95% confidence interval: 0.56-1.48). In the vitamin group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (Unadjusted Odds Ratio: 1.61 (95% confidence interval: 0.88-2.93). 166 patients in the PP analysis reported an infection (Unadjusted Odds Ratio: 0.91 (95% confidence interval: 0.55-1.50), 23 reported a serious infection (Unadjusted Odds Ratio: 2.57 (95% confidence interval: 1.02 -6.46). None of the patients was hospitalized due to serious infection.

Conclusion
An over the counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators and/or biological therapy.