bluuebunny/crossref_metadata_2025_split huggingface dataset:
P515 Infliximab desensitization in patients with Inflammatory Bowel Diseases: a safe therapeutic alternative
Authors: Hammoudi N , Hassid D , Bonnet J , Tran Minh M L , Baudry C , Chedouba L , Vauthier A , Gornet J M , Allez M 
Published: January 2023

Abstract

Background
Infliximab (IFX) is a humanized monoclonal anti-TNF antibody widely used for the treatment of Inflammatory Bowel Diseases (IBD). Hypersensitivity reactions (HSR) to the administration of the drug are not rare. Their occurrence usually leads to permanent drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR.

Methods
We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Clinical data on IBD were collected. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after were collected. Clinical outcome and recurrence of HSR were evaluated.

Results
From 2005, 27 patients (Female: 18 (66%), Median age at IBD diagnosis: 18.1 (15.6-28.2)) were included. Among these 27 patients, 26 (96%) had Crohn’s Disease, 17 (62%) a history of surgery, 14 (52%) an ileal disease location and 7 (26%) were smokers. It was an immediate HSR in most patients, classified as severe (n=13) or moderate (n=12), and a delayed HSR in only 2 patients. Eleven (41%) patients were treated with immunosuppressants as combination therapy at time of HSR. In most cases (n=18, 66%), HSR occurred at IFX reintroduction after a drug interruption, and in most of these cases after one or two infusions. For 9 (33%) patients, HSR occurred during a maintenance treatment with IFX after a median time of 38 months with 5 moderate and 4 severe reactions.
Desensitization was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants as combination therapy.
IFX was well tolerated, without recurrence of HSR in 19 (70%) patients, and 12 had a clinical response at 6 months. Eight were still treated with IFX (30%) at 1 year. Eight (30%) patients presented a HSR at first (n=2), second (n=4) or third (n=2) IFX perfusion. Five were moderate with only cutaneous manifestations and 3 were severe. None led to intensive care unit transfer or death. All led to definitive drug discontinuation.
Female gender and young age at desensitization were significantly associated with long term continuation of IFX (p=0.05 and p=0.03 respectively).
ADA and IFX trough levels were available for 14 patients at time of desensitization. All except 2 had ADA. Among patients who were treated with IFX for a long-term period, 7 had drug levels available at desensitization and 6 months later. All had ADA at baseline. At 6 months, four reduced their level of ADA, 2 had no ADA and a significant trough level of IFX.

Conclusion
IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.
P524 Predictors of immunogenicity in patients with Inflammatory Bowel Disease treated with infliximab: A post hoc analysis of the randomised phase I CT-P13 SC study
Authors: Schreiber S , Ben-Horin S , Ye B D , Kim D H , Reinisch W 
Published: January 2023

Abstract

Background
CT-P13 SC is the only subcutaneous (SC) formulation of infliximab (IFX) approved to treat Crohn’s disease (CD) or ulcerative colitis (UC). The primary CT-P13 SC study reported no increased risk of immunogenicity (anti-drug antibody [ADA]/neutralising antibody [NAb] positivity) with CT-P13 SC vs. intravenous (IV) in CD or UC patients (pts) despite a numerical trend for lower ADA/NAb positivity with SC dosing.1 It is unclear whether high trough levels (Ctrough) during IFX dosing may account for these observations.

Methods
This post hoc analysis of part 2 of the randomised, parallel-group CT-P13 SC study (NCT02883452) evaluated predictors of immunogenicity in CD or UC pts treated with CT-P13. The relationship of Week (W) 22 and 30 ADA and NAb positivity rates with W22 CT-P13 Ctrough, under stable dosing, was examined. The optimal threshold of Ctrough for predicting ADA positivity was estimated by receiver operating characteristic (ROC) methodology using W22 data. A generalised linear regression model identified predictive factors for ADA and NAb positivity at W22 and W30. The proportion of pts with Ctrough levels equal to or above the calculated predictive threshold, and ADA/NAb positivity rates, were determined by treatment arm.

Results
The analysis included 131 pts randomised at W6 to receive CT-P13 SC (n=66) or CT-P13 IV (n=65) as maintenance treatment. Of 113 pts with both Ctrough and immunogenicity data available at W22, 60 were ADA negative, and 53 were ADA positive. At W22, median Ctrough levels were significantly higher in the ADA-negative vs. ADA-positive group (16.95 vs. 3.44 μg/mL, p&lt;0.0001); ADA positivity differed significantly according to Ctrough quartile (p=0.0009; Fig. 1).

ROC analysis showed that a Ctrough threshold of 4.695 μg/mL optimally predicted ADA positivity with 66.2% sensitivity and 77.3% specificity (area under the ROC curve, 0.766 [95% confidence interval, 0.664–0.869]; Fig. 2).

Concomitant medication use and W22 Ctrough ≥4.695 μg/mL were significantly associated with lower rates of ADA and NAb positivity at W22 and were significant predictors of lower rates of ADA and NAb positivity at W30 (Fig. 3).

At W22, a higher proportion of pts had Ctrough ≥4.695 μg/mL in the SC vs. IV arm (96.5% vs. 25.0%, p&lt;0.001). In the SC vs. IV arm, the proportion of pts with ADA and NAb positivity was significantly lower at W22 (ADA, 36.8% vs. 57.1%, p=0.039; NAb, 7.0% vs. 21.4%, p=0.033; Fig. 4).

Conclusion
Ctrough level predicted ADA and NAb positivity in CD or UC pts, with levels ≥4.695 μg/mL significantly associated with lower rates of positivity, providing initial evidence on high zone tolerance of IFX.
Reference:
1. Schreiber S et al. Gastroenterology 2021;160:2340–2353.
P527 Leucine-rich alpha 2 glycoprotein- A useful biomarker to discriminate mucosal healing in CRP-negative ulcerative colitis
Authors: Tanaka A , Kanmura S , Maeda N , Kuwazuru K , Komaki F , Komaki Y , Ido A 
Published: January 2023

Abstract

Background
The long-term treatment goals for inflammatory bowel disease including ulcerative colitis (UC) have shifted from clinical remission to mucosal healing. However, frequent endoscopies are a great burden on the patients. Leucine-rich alpha 2 glycoprotein (LRG) is produced by hepatocytes, neutrophils, and the intestinal epithelium. Therefore, it is speculated to be more gut-specific than C-reactive protein (CRP) level. This study examined whether LRG could be used as a biomarker to determine the presence or absence of mucosal healing in patients with CRP-negative UC. Furthermore, we examined whether it was useful for each type of lesion extension.

Methods
The subjects of this study were CRP-negative UC patients who visited our department from May 2021 to October 2022, had their LRG measured, and underwent imaging evaluation by colonoscopy. We analysed the patients’ clinical background, the ROC-AUC of LRG for mucosal healing, the cut-off value of LRG to discriminate mucosal healing, and the cut-off value of LRG to discriminate mucosal healing by the type of extension of lesions. Endoscopic evaluation was performed within 3 months before and after the LRG measurement. The upper limit of the normal CRP value was set to &lt;3 mg/L.

Results
A total of 57 cases were analysed; 30 (53%) were men. The median age (range) of onset was 31.1 years (8-67 years). The median disease duration (range) was 6.8 years (0-40). Pancolitis occurred in 41 (72%) cases. Left-sided colitis and proctitis occurred in 16 (28%) patients. The median (range) LRG was 11.2 μg/ml (6.5-34.4 μg/ml). The ROC-AUC of LRG for mucosal healing was 0.576 (95% confidence interval 0.441-0.711). The cut-off value of LRG for discriminating mucosal healing was 12.6 μg/ml (sensitivity 0.373, specificity 0.913). 3) The cut-off value for pancolitis was 12.6 (0.857, 0.439), and that for left-sided colitis or proctitis was 9.4 (0.556, 0.800).

Conclusion
In CRP-negative UC patients, LRG can be used as a biomarker for discriminating between the presence and absence of mucosal healing. It may also help distinguish types of extension.
P528 Effectiveness, Safety and Incremental Costs of Proactive Therapeutic Drug Monitoring of Infliximab in a Prospective Cohort of Inflammatory Bowel Disease Patients
Authors: Zelinkova Z , Podmanicky D , Kadleckova B 
Published: January 2023

Abstract

Background
The use of infliximab (IFX) is limited by low treatment persistence. Proactive therapeutic drug monitoring (pTDM) has been shown to increase the treatment persistence in inflammatory bowel disease (IBD) patients but the real-life data evaluating effectiveness, safety and costs of this approach are scarce. Therefore, the aim of this study was to assess survival on treatment, safety and costs of pTDM of IFX in the treatment of IBD.

Methods
IBD patients who started IFX in a referral centre using pTDM between January 2018 and March 2021 were included. The main outcomes were treatment persistence, adverse events and incremental costs of pTDM.
IFX trough levels were assessed in the week 14 and subsequently every six months by commercially available ELISA kit (Ridascreen R-Biopharm) and with the cut-off level of 3μg/ml .
Costs related to the measurements of levels and the costs of intensified treatment were calculated. The costs of pTDM were compared with costs of a modelled cohort using reactive TDM (rTDM) based on the data from the same cohort. The model used arbitrarily determined intensification regimen to 5mg/kg of IFX every 4 weeks in case of pharmacokinetically determined clinical or endoscopic loss of response. The calculation was performed for the first year of treatment.

Results
Overall, 99 patients with IBD were included (58 men – 59%; mean age 39,96 years, minimum-maximum, 20-73 years; 64% patients with Crohn′s disease; mean disease duration 103 months, minimum – maximum, 8-402 months).
The treatment was intensified in 57 patients (58%). Overall treatment survival using pTDM was 87% at 6 months, 77% at one year, 66% at two years and 60% at both, the third and fourth year of treatment. There were no differences between patients on conventional regimen vs. intensified regimen with regards to adverse events.
The costs related to pTDM in this cohort of 99 patients were € 90 306,56 while the costs of the modelled cohort using rTDM were € 24 846,30. The overall incremental costs were thus € 65 460,26 with mean costs per patient for the first year of treatment of € 661,21.

Conclusion
Proactive TDM of IFX results in a steady 60% treatment persistence beyond the second year of treatment with no impact on the safety. In the context of this solid treatment persistence, the incremental costs related to proactive TDM seem negligible when considering the costs of alternative biologicals used in case of loss of response to IFX.
P530 The Burden on Cohabitants of Patients with Inflammatory Bowel Disease: A Cross-Sectional Study
Authors: López-Vico M , Sánchez-Capilla A D , Martín-Rodríguez M D M , Cabello-Tapia M J , Redondo-Cerezo E 
Published: January 2023

Abstract

Background
Inflammatory bowel disease is a chronic disease characterized by digestive symptoms with an increasing incidence and prevalence. It is well established its impact on the quality of life of patients and their main caregivers but no study has yet considered the consequences of IBD on cohabitants with no direct involvement in patient`s care. Our aims were to analyze quality of life in cohabitants of people with IBD and identify potential related factors.

Methods
We conducted a cross-sectional study that included patients with IBD and their house-hold members. Participants were recruited from a period of two months from patients attending the IBD unit of our hospital. Inclusion criteria were a definite diagnosis of IBD and household members living in the same house for a period of 1 year or more. Exclusion criteria were an age &lt;18, refusal to participate or subjects unable to fulfill the questionnaires.
Demographic data was obtained for patients and household members.
IBD activity was assessed by using the Partial Mayo Score and the Harvey-Bradshaw score. Other relevant information regarding the prior and current state of the disease was collected.
Quality of life was assessed in the case of the patients with the Inflammatory Bowel Disease Questionnaire (IBDQ-32) and for the household members we used the Household Members Quality of Life-Inflammatory Bowel Disease (HHMQoL-IBD) questionnaire.

Results
We included 22 patients with UC, 32 patients with CD and 2 patients with indeterminate colitis and 82 household members. Both groups had similar sociodemographic characteristics.
The univariate analysis of the quality of life of cohabitants showed a significant association of HHMQoL-IBD and IBDQ-32 score in their relatives (p&lt;0.0001) (Figure 1), last CRP (p=0.043), number of disease flares in the last year (p=0.04), extraintestinal diseases (p=0.01) and particularly articular disease (p=0.04).
Cohabitants of patients with CD had significantly lower HHMQoL-IBD than UC ones (53 ± 18 vs. 62 ± 23; p=0.049).
Among cohabitants of patients with UC and CD, patient’s CRP in the last control was related to HHMQoL-IBD score (p=0.043 and p=0.04 respectively).
In a linear multiple regression analysis, IBDQ-32 score (p&lt;0.0001) in patients and the presence of extraintestinal disease (p=0.048) were independent predictors of cohabitant’s quality of life, and particularly articular disease.

Conclusion
Quality of life in household members of patients with IBD is related to patient’s quality of life and extraintestinal conditions related to the disease. Our study shows how important is to analyze and act in the patient’s whole environment, taking into consideration not only clinical variables but also the relational conditions and impact of the disease.
P536 Is there any association between fat body mass and bone mineral density in patients with Inflammatory Bowel Disease?
Authors: Ratajczak A E , Michalak M , Szymczak-Tomczak A , Rychter A M , Zawada A , Skoracka K , Dobrowolska A , Krela-Kaźmierczak I 
Published: January 2023

Abstract

Background
Low bone mineral density (BMD) in inflammatory bowel disease (IBD) is multifactorial and includes nutritional status. The study aimed to look for the association between fat body mass and fat-free mass and BMD of the lumbar spine (L1-L4), femoral neck and total body.

Methods
The study subjects included 95 patients with Crohn’s disease (CD), 68 with ulcerative colitis (UC) and 40 healthy adults (control group - CG) in age of 18-50 years old, recruited at the Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences between 2020-2021. The summary of the methods is presented in Figure 1.

DXA- Dual-energy X-ray absorptiometry

Results
A lowered fat mass percentage occurred in about 8% of CD, 13% of UC and 3% of CG. Additionally, an increased percentage of fat mass occurred above 50% of CD, 40% of UC and about 60% of CG. It is interesting because the median, lower and upper quartile for BMI (body mass index) was normal for CD [21.70 (19.20; 24.40] and UC [20.30 (18.45; 24.05)]. Fat body mass and fat mass percentage were significantly lower among UC compared with the CG and CD in women but not men. Additionally, healthy women presented higher fat-free mass than CD and UC women. We did not find the same differences for men. In CD women, but not men, with a high body fat percentage, we find a higher BMD and T-score of L1-L4-but than the standard body fat percentage. Fat body mass correlated positively with BMD and T-score of L1-L4 and total body in men with UC but not in men with CD and women with UC. However, we find a positive correlation between fat body mass and BMD and T-score of L1-L4, femoral neck and total body. Among CG, positive correlations occurred between the fat body mass and BMD of L1-L4, BMD of total body and T-score of total body, but only in men. Fat-free mass correlated positively with BMD and T-score of L1-L4 and total body and BMD, T-score and Z-score of the femoral neck in CD women but not UC women. In men, correlations occurred between the fat-free mass and BMD and T-score of L1-L4, femoral neck and total body in CD. Among UC, fat-free mass correlated with BMD, T-score, and Z-score of L1-L4, femoral neck and total body. We did not find a correlation in CG. CRP (C-reactive protein) correlated negatively with fat body mass only in men with CD and negatively in healthy women.

Conclusion
A higher fat mass percentage is common among IBD patients and healthy adults despite normal BMI. Probably, fat body mass and fat-free mass are predictors of nutritional status and the course of the disease, therefore correlated positively with BMD, T-score and Z-score. On the other hand, a high-fat mass percentage with a normal BMI indicates metabolic obesity with normal weight.
P545 Does gender matter? Gender-related nutritional behaviour, disease activity and quality of life in patients with inflammatory bowel diseases
Authors: Pueschel L , Kockelmann F , Kueck M , Tegtbur U , Seidler U , Lenzen H , Attaran-Bandarabadi M , Bachmann O , Wedemeyer H , Wiestler M 
Published: January 2023

Abstract

Background
The latest research clearly indicates that diet plays an important role in the onset and course of inflammatory bowel diseases (IBD). But especially data on gender specific aspects of diet in IBD patients are still lacking even though we know from the general population that gender matters in case of diet.

Methods
We hypothesised an interaction of gender and diet in IBD patients and that this is linked to disease behaviour. In a subgroup analysis of a previously published prospective trial (Wiestler M. et al., Clinical and Translational Gastroenterology, 2019) 91 IBD patients were stratified into 4 groups (Crohn’s disease - CD [n=50] and ulcerative colitis – UC [n=41], female and male, respectively) to compare nutritional behaviour by sex and diagnosis. We evaluated disease-specific quality of life (IBDQ), physical activity (accelerometery), body composition (bioelectrical impedance analysis (BIA)), as well as clinical (HBI, SCCAI) and biochemical (CRP, faecal calprotectin) parameters of disease activity in comparison to nutritional behaviour (food frequency questionnaire (FFQ)).

Results
The nutritional behaviour of CD patients showed significant gender-related trends and differences in correlation with disease activity (Spearman correlation analysis). In male CD patients HBI significantly negatively correlated with the amount of fish (p=0.005, r=-0.612) and meat consumed per month (p=0.023, r=-0.519). In female CD patients the amount of fish consumed per month significantly negatively correlated with the IBDQ score (p=0.029, r=-0.438).
The nutritional behaviour of UC patients showed significant gender-related trends and differences in correlation with disease activity as well. In female patients SCCAI significantly negatively correlated with the amount of cake, pie/ sweet baked goods (p=&lt;0.001, r=-0.832) and significantly positively correlated with the amount of poultry consumed per month (p=0.006, r=0.715). Furthermore, in female patients the amount of pizza consumed per month significantly positively correlated with the IBDQ score, subscore social (p=0.016, r=0.653).

Conclusion
In this subgroup analysis of a cross-sectional study, nutritional behaviour of IBD patients showed significant gender-related differences in correlation with disease activity and disease related quality of life. Due to the close correlation between IBD and nutrition and the different nutritional needs according to disease activity, our results illustrate the importance of gender-sensitive collection of a nutritional history as well as the need for gender-sensitive nutritional recommendations in IBD patients to further optimize individual patient care.
P550 Characterisation of hospitalised patients with ulcerative colitis treated with tofacitinib in the OCTAVE clinical programme for up to 7.8 years
Authors: Taxonera C , Ha C , del Pilar Fortes M , Gardiner S , Mundayat R , Ghosh S , Connor S J 
Published: January 2023

Abstract

Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in the OCTAVE clinical programme.1,2 Here, we present an analysis of the number and causes of UC-related hospitalisations during the OCTAVE clinical programme.

Methods
This descriptive analysis comprised patients (pts) hospitalised for UC who received placebo or tofacitinib 10 mg twice daily (BID) in OCTAVE Induction 1&2 (NCT01465763; NCT01458951)1, and pts who received placebo, or tofacitinib 5 or 10 mg BID in OCTAVE Sustain (NCT01458574)1, or ≥1 dose of tofacitinib in OCTAVE Open (NCT01470612)2; it includes data from pts with ≤7.8 years of tofacitinib exposure. We examined the demographic and clinical characteristics, proportions, causes and other aspects of UC-related hospitalisations in pts treated with placebo or tofacitinib in the OCTAVE clinical programme.

Results
Overall, 1139 pts with UC were included in this analysis. Demographic and disease characteristics of pts with UC-related hospitalisations were generally similar across treatment groups in each study; most pts were &lt;40 years old, had pancolitis, a mean total Mayo score &gt;8, prior treatment with oral corticosteroids and immunosuppressants (Table 1). Ninety-five pts had UC-related hospitalisations; of whom 92 had one UC-related hospitalisation and 3 pts were hospitalised twice (Table 2). In OCTAVE Induction 1&2, OCTAVE Sustain and OCTAVE Open, 2.1%, 1.0% and 6.6% of pts, respectively, had UC-related hospitalisations with tofacitinib 10 mg BID vs 1.0% and 2.9% of pts receiving tofacitinib 5 mg BID in OCTAVE Sustain and OCTAVE Open, and 3.4% and 4.0% of pts receiving placebo in OCTAVE Induction 1&2 and OCTAVE Sustain, respectively. UC-related hospitalisations did not lead to temporary treatment discontinuations in most pts (Table 2). The most frequent cause of UC-related hospitalisations in tofacitinib- and placebo-treated pts was non-surgical UC-related events (ie, UC flares; Table 2).

Conclusion
UC-related hospitalisations were infrequent in the OCTAVE clinical programme, and rates were generally lower than those reported in a real-world assessment of pts with UC treated with biological therapies.3 Most hospitalised pts were aged &lt;40 years with severe disease and prior corticosteroid and immunosuppressant exposure. The most common cause of hospitalisation was non-surgical UC-related events.
References:
1. Sandborn WJ et al. N Engl J Med 2017;376:1723-1736.
2. Sandborn WJ et al. Aliment Pharmacol Ther 2022;55:464-478.
3. Bressler B et al. J Crohn’s Colitis 2021;15:1694-1706.