bluuebunny/crossref_metadata_2025 huggingface dataset:
P502 Application of an algorithm-based precision-dosing model to a real-world cohort of patients on infliximab maintenance therapy: implications for drug usage and cost
Authors: Nguyen A , Gibson P , Upton R , Mould D , Sparrow M P
Published: January 2023

Background

Infliximab is registered for use in patients with inflammatory bowel disease (IBD) at an intravenous maintenance dose of 5 mg/kg eight-weekly. Secondary loss of response during maintenance therapy occurs in up to 50% of patients. New precision dosing models, which forecast infliximab doses to achieve targeted trough levels, reduce non-response and improve patient outcomes. Aim: To compare standard 5 mg/kg eight-weekly infliximab dosing to the infliximab doses theoretically required to achieve predefined infliximab trough target levels, as determined by the iDOSE® precision dosing dashboard model.

Methods

IBD patients treated with eight-weekly maintenance infliximab therapy dosed at 5 mg/kg were included. A recorded infliximab dose was considered dose X if the following was available: three previous infliximab doses, albumin and C-reactive protein at time of dose X, trough infliximab level immediately preceding dose X and the patient’s weight. The Baysient LLC iDOSE® software was then used to predict dose X to maintain therapeutic infliximab trough levels of ≥ either 5-10 or 3-7 µg/ml until the next eight-weekly dose. The predicted dose X was compared to the actual dose X given.

Results

174 patients (56% male) were included with 417 dose X recordings. Of those, 135 had Crohn’s disease, 31 ulcerative colitis and 8 IBD-unclassified. Median age was 36 (IQR 29-47) years with a disease duration of 5 (1-13) years. 76% of patients were receiving immunomodulators and 6% were smokers. Duration of infliximab therapy before dose X was 2 (0-4) years. Trough infliximab levels were 5.0 (2.5-7.6) µg/ml, serum albumin was 38 (35-40) g/L and C-reactive protein 3 (3-4) mg/L. Comparing actual dose X with predicted dose X, 52% and 32% of doses were subtherapeutic when aiming for trough levels of 5-10 and 3-7 µg/ml respectively. The underdosing occurred by 5.6 and 5.3 mg/kg per dose, respectively. Cost analysis showed total costs increased by 102% and 29% when aiming for trough levels 5-10 and 3-7 µg/ml. On multivariable regression analysis, significant associations with subtherapeutic infliximab levels were ulcerative colitis compared to Crohn’s disease [OR: 9.81, 95% CI: 1.28-75.40, p = 0.028] and pre-dose X infliximab trough level [OR: 0.07, 95% CI: 0.03-0.15, p < 0.001].

Conclusion

More than half of maintenance infliximab drug doses given at our institution were too low to achieve therapeutic infliximab blood levels of at least 5 µg/ml. These patients would likely benefit from an increased dose or reduced dosing interval of infliximab. These findings need to be confirmed prospectively.
P505 Real word long-term efficacy and safety of vedolizumab in managing ulcerative colitis versus crohn’s disease: results from “long vedo” italian multicenter study
Authors: Mocci G , Maconi G , Onidi F M , Cataletti G , Elisei W , Scaldaferri F , Lorenzetti R , Pagnini C , Scarcelli A , Graziani M G , Di Paolo M C , Pranzo G , Luppino I , Monterubbianesi R , Faggiani R , Ferronato A , Savarino E , Pica R , Cocco A , Rodino S , Sebkova L , Zampaletta C , Gaiani F , Fanigliulo L , Allegretta L , Cuomo A , Donnarumma L , Della Valle N , Forti G , Antonelli E , Bassotti G , Iannelli C , Aragona G , Lauria A , Piergallini S , Colucci R , Binaghi L , Meucci C , Papa A , Tursi A
Published: January 2023

Background

Current data about long-term use of vedolizumab (VDZ) in ulcerative colitis (UC) versus Crohn’s disease (CD) patients are limited. We aimed to assess whether there are differences in term of long-term efficacy and safety of VDZ in UC vs. CD patients.

Methods

Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission within 6 month of treatment, maintenance of clinical remission during a long follow-up, and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), steroid discontinuation, and treatment optimization during the follow-up.

Results

The study group consisted of 729 patients (475 patients with UC and 254 CD patients with CD) with a median follow-up of 18 (interquartile range 6-36) months. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients, higher in CD patients (74.4 vs. 62.9, p<0.000) while, at the maximal follow-up, it was achieved and maintained in 81.5% of patients (UC vs. CD, p=0.667). At uni- and multivariate analysis, reaching clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics were significantly associated with longer clinical remission (p<0.0001). Long-term follow up clinical response was significantly higher in UC vs. CD (p=0.023) and surgery occurred more frequently in CD (p=0.04), while no difference were found between UC and CD about the other secondary endpoints

Conclusion

Overall, no significant differences were found about the long-term use of VDZ in UC vs. CD. However, we identified some parameters the can help the physician to predict the long-term efficacy of this drug.
P507 United States and European patient perspectives on the impact of moderate-to-severe Ulcerative Colitis on sexual activity: Communicating Needs and Features of IBD Experiences (CONFIDE) survey
Authors: Travis S , Bleakman A , Dubinsky M , Rubin D , Panaccione R , Hibi T , Kayhan C , Gibble T H , Sapin C , Flynn E , Atkinson C , Schreiber S
Published: January 2023

Background

Patients with ulcerative colitis (UC) report that UC negatively affects their quality of life (QoL), including sexual functioning, satisfaction, and drive.1,2 These effects are rarely discussed with or by gastroenterologists in clinical practice. The CONFIDE study aims to elucidate the impact of symptoms on the lives of patients with moderate-to-severe UC in the United States (US), Europe (EU5; France, Germany, Italy, Spain, and UK), and Japan. Data presented here are from the US and EU5.

Methods

Online, quantitative, cross-sectional surveys were conducted (July–September 2021). Criteria based on previous treatment, steroid use, and/or hospitalization were used to define moderate-to-severe UC. Data collected included patient perspectives on the impact of UC on sexual activity. Sexual activity was not limited to intercourse and included activities such as masturbation.

Results

Surveys were completed by 200 US patients (male [M]=62%, mean age 40 years) and 556 EU5 patients (M=57%, mean age 39 years). Of these, 77% US and 54% EU5 patients were receiving advanced therapy (biologic/novel oral) and 52% and 73% were receiving steroids at the time of survey completion, respectively. Overall, 63% US patients (M=55%, female [F]=77%) and 53% EU5 patients (M=47%, F=60%) reported avoiding or decreasing sexual activity due to UC in the 3 months prior to the survey (Figure 1a). Among these patients (US: N=126; EU5: N=292), most frequently reported reasons for avoidance of sexual activity were bowel urgency (BU; 41%), decreased sexual desire (37%), and fear of BU-related accidents (34%) in the US and fear of faecal seepage (37%), fear of BU-related accidents (36%), and BU itself (31%) in EU5 (Figure 1b). Although reasons for avoiding sexual activity were broadly similar between sexes, higher percentage of male patients from both US and EU5 (US: M=33%, F=24%; EU5: M=42%, F=33%) reported fear of faecal seepage as a factor affecting sexual activity. Conversely, higher percentages of female patients reported perianal pain (M=13%, F=19%) and self-consciousness (M=13%, F=24%) as reasons for avoiding sexual activity in the US and decreased sexual desire (M=16%, F=26%), BU (M=26%, F=36%) and fatigue (M=14%, F=22%) in EU5 (Figure 2).

Conclusion

In both US and EU5 populations, >50% patients with moderate-to-severe UC reported avoiding or decreasing sexual activity due to UC, with bowel urgency and bowel urgency-related accidents being among the top three reasons. In addition to other QoL parameters, impact of UC on patients’ sexual health needs to be assessed in routine clinical practice.

References:

1Bulut AE, et al. Turk J Gastroenterol. 2019;30:33-39.

2Jedel S, et al. Inflamm Bowel Dis. 2015;21:923-38.
P508 Sarcopenia is associated with increased rates of infectious post-operative complications in Crohn’s disease patients
Authors: Simpson K , Inniss S , Fragkos K C , Wood C P J , Smith A , Rahman F Z
Published: January 2023

Background

More than one fifth of Crohn’s disease patients will require surgery within 5 years of diagnosis, rising to over 90% throughout their lifetime. Sarcopenia is defined as a disease process of skeletal muscle decline in mass, function, and physical performance. Emerging evidence suggests sarcopenia may be implicated with Crohn’s disease severity and poorer outcomes. Several sarcopenia assessment tools exist with varying accuracy, however CT or MR images at the level of the third lumbar vertebra (L3) can reliably predict whole-body composition. Our aim was to assess the prevalence of sarcopenia via L3 scores in pre-operative Crohn’s disease patients and examine its impact on post-operative outcomes.

Methods

This single-centre, retrospective study collected data from 95 Crohn’s disease patients undergoing surgery between 2015-2021 and followed up for 12 months. Pre-operative baseline characteristics and post-operative outcomes were recorded immediately after surgery and at 30 days, 1, 6 and 12 months. Infectious and non-infectious complications were recorded, including but not limited to: abscess, collection, wound site infection, anastomotic leak, venous thromboembolism, haemorrhage. Sarcopenia was assessed from CT and MR imaging at the level of L3 within 3 months of surgery, and was defined as per the Martin et al. equation.

Results

Of 58 Crohn’s disease patients with pre-operative imaging, sarcopenia was prevalent at 74.1% (43/58). Pre-operative Harvey-Bradshaw Index was significantly higher in those with sarcopenia (sarcopenic group: 8, non-sarcopenic: 4, p<0.001). In addition, anaemia adjusted for gender was more prevalent in the sarcopenic group versus non-sarcopenic (56.1% [23/41] versus 25% [3/15], p=0.058). Sarcopenic patients experienced higher rates of infective complications within 30 days of surgery (22.5% [9/40] versus 0, p=0.052).

Conclusion

The prevalence of sarcopenia is higher in Crohn’s disease patients undergoing surgery than first thought and may be implicated in disease severity. Our study found that sarcopenia is associated with increased rates of infective post-operative complications. Further studies are required to corroborate our findings and identify appropriate interventions for sarcopenia. In conclusion, sarcopenia in Crohn’s disease may reflect a phenotype of aggressive disease implicated with worse post-operative outcomes.
P511 Evaluation of home faecal calprotectin testing to aid remote management and enhanced self-management of Inflammatory Bowel Disease.
Authors: Allen K , Munuswamy P
Published: January 2023

Background

Faecal calprotectin (FC) is an established biomarker for patients with irritable bowel disease (IBD). A treat to target strategy has been shown to be successful in managing these patients and the development of a home FC test (IBDoc) opens the door to a more patient centred approach for IBD management.

Methods

IBD patients in the IBD database at Basildon and Thurrock University Hospital with a compatible smart phone who had previously agreed to monitor FC at home using IBDoc were eligible for inclusion. Usability, patient experience, engagement and understanding of the IBDoc, along with satisfaction with enhanced remote and self-management, were assessed using a mixed methods approach via an online questionnaire consisting of Likert scale questions and a limited number of free text questions.

Results

47 participants were enrolled in the study. Over 85% of responses showed patients found the IBDoc to be user friendly. Over 80% of responses indicated patients were happy with their understanding of the result and what it meant for their disease status. Thematic analysis revealed a personalised care plan for each patient is of crucial importance. Clinicodemographic variables found to influence patient satisfaction with use of the IBDoc and enhanced remote and self-management were treatment type, education history and disease type.

Conclusion

Results demonstrate excellent acceptance of the IBDoc system with good scores for usability and patient understanding. This shows that the home test can be used as an objective patient reported outcome within a treat to target approach. Better educational materials and clinically guided personalised care plans, along with the IBDoc home FC test, make IBD a viable candidate for self-management at the same level as traditionally self-managed diseases such as diabetes.
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

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

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<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<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

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 <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

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

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 <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<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<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

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

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=<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

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 <40 years old, had pancolitis, a mean total Mayo score >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 <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.
P551 Platelet-to-lymphocyte ratio index for non-invasive assessment of endoscopic activity in small bowel Crohn’s disease: application and prospective validation.
Authors: Macedo Silva V , Ferreira A I , Lima Capela T , Arieira C , Cúrdia Gonçalves T , Boal Carvalho P , Dias de Castro F , Moreira M J , Cotter J
Published: January 2023

Background

The platelet-to-lymphocyte ratio (PLR) index has recently been a focus of investigation as a reliable marker of inflammation, being shown to have a good accuracy upon predicting endoscopic remission in patients with colonic Crohn’s Disease (CD). We aimed to evaluate and validate the discriminative power of PLR index in patients with small bowel CD.

Methods

Single center study including patients with isolated small bowel CD (L1 ± L4 disease according to Montreal classification) undergoing small bowel capsule endoscopy (SBCE) for assessment of endoscopic activity. CD endoscopic activity was classified according to the Lewis score (LS) value. Complete blood count, C-reactive protein and fecal calprotectin values were collected within 1 month of SBCE.

A retrospective sample was used for initial assessment of PLR index performance, followed by a prospective 2-years application on a distinct sample.

Results

The initial sample included 49 and the validation sample 48 patients, both groups being age- and gender-matched.

On the initial cohort, PLR index presented a positive moderate correlation with LS (k=0.597; p<0.001), which was stronger than the one found with fecal calprotectin (k=0.525; p=0.001) or C-reactive protein (k=0.321; p=0.029). PLR index presented an excellent accuracy for predicting patients with a moderate-to-severe endoscopic activity (AUC=0.91; 95%CI=0.82-0.99; p<0.001), and a good accuracy for prediction of mucosal healing (AUC=0.74; 95%CI=0.60-0.89; p=0.007).

These results were confirmed on the prospective validation cohort, as the correlation of LS with PLR index (k=0.631; p<0.001) was further stronger than with fecal calprotectin (k=0.355; p=0.040) and C-reactive protein (k=0.183; p=0.219). The accuracy of PLR index was confirmed to be excellent for moderate-to-severe endoscopic activity (AUC=0.87; 95%CI=0.76-0.98; p<0.001) and good for mucosal healing (AUC=0.74; 95%CI=0.59-0.87; p<0.001).

Conclusion

PLR index demonstrated an excellent acuity in predicting moderate-to-severe disease and good acuity in predicting mucosal healing in patients with small bowel CD, with both associations confirmed on a prospective validation cohort. Our findings establish this index as a promising and easy-to-apply tool for non-invasive and regular follow-up of patients with small bowel CD.
P556 Surgery in high-risk paediatric Crohn’s Disease treated with up-front anti-TNF agents and long-standing biologic therapy
Authors: Musto F , Distante M , Dei Rossi E , Calicchia A , Veraldi S , Mondi’ F , Tarani F , D’Arcangelo G , Aloi M
Published: January 2023

Background

High-risk (HR) Crohn’s Disease (CD) is associated with high surgical and progression rates. Therefore, recent ESPGHAN guidelines (GL) suggest starting an early anti-TNFα treatment to modify the natural history of the disease. The aim of our study was to evaluate the surgical rate in a population of HR-CD paediatric patients treated with up-front anti-TNFα agents and long-standing biologic therapy

Methods

This is a retrospective, observational, single-center study conducted at the Paediatric Gastroenterology, Hepatology, and Endoscopy Unit at Policlinico Umberto I Hospital – Sapienza University of Rome. We collected data from all patients diagnosed with CD under 18 years, with a minimum follow-up of 12 months. between June 2008 to July 2022. Patients were then stratified at the diagnosis into HR and LR, based on ESPGHAN GL criteria. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at 6, 12, 24, 36, 48, and 60 months

Results

130 patients were enrolled, 76 HR (58%) and 54 LR (42%) [median age 12.5 (IQR) yrs, female 45 (35%), medium follow-up 54±24 months]. The HR group included 39 patients (51%) with panenteric disease, 15 (20%) with a structuring behavior (B2), 3 (4%) with structuring/penetrating disease (B2-B3), and 26 (34%) with perianal involvement (p). Early anti-TNFα agents were started in 80% of patients <6 months from the diagnosis, while 15 (20%) started biological therapy between 6 and 12 months from the diagnosis. All patients continued biologic therapy throughout the study follow-up: 20 (26%) optimized anti-TNF, 25% switched biologic, 11% added an immunomodulator, and 4% combined 2 biological drugs. The surgical rate at 5 years was 29% (n=22) and 29% n=16) in HR and LR groups respectively (p-value 1,0). Eleven % (n=8) of HR patients needed surgical resection, while perianal surgery (seton drainage, fistulotomy, fistulectomy) was performed in 18% (n=14), with no significant difference with LR group [(intestinal resection 18% (10/55), perianal surgery 11% (6/55), p > 0.05]. Perianal disease resulted positively associated with surgical risk (p 0.002, OR 5.62 CI 1.84-17.15) while small bowel imaging at the diagnosis was a protective factor for surgery (p 0.017, OR 0.23 CI 0.07-0.77). No significant difference was found in the interval free from surgery between HR and LR, although HR children mainly needed surgery in the first 12 months after the diagnosis.

Conclusion

Our data suggest that paediatric patients with HR-CD treated with early anti-TNF agents and long-standing biologic therapy have a similar disease course and surgical risk to those with LR disease. At a 5-year follow-up, one-third of patients needed surgery, mainly in the first year after the diagnosis
P557 Analysis of colectomy rates and advanced therapy prescribing for ulcerative colitis in Lothian; Scotland an updated population based cohort study
Authors: Jenkinson P , Plevris N , Gros Alcalde B , Lyons M , Derikx L , Constantine-Cooke N , Arnott I , Jones G , Lees C
Published: January 2023

Background

The impact of advanced therapies on colectomy rates in UC remains unclear. We have published a population-based cohort reporting patterns of advanced therapy prescribing and the impact on colectomy rates complete to 2018 The aim of this study was to describe recent trends by extending the study period to 2021.

Methods

The Lothian IBD registry (LIBDR) is a manually validated, comprehensive, population dataset of the Edinburgh area . The LIBDR contains measured point prevalence between 2008-2018 and estimated prevalence from 2018-2028 (derived from AARIMA modelling). All patients with a diagnosis of UC who commenced advanced therapy or underwent a colectomy in Lothian, Scotland between 01/01/2005 and 31/12/2021 were included interrogating multiple clinical and administrative databases. Linear and segmental regression analyses were used to identify the annual percentage change (APC) and temporal trends (statistical joinpoints) in colectomy rates and drug initiation. Kaplin Meier curves were created for drug ersistence and compared with the log rank test.

Results

484 patients underwent colectomy for UC between 2005 and 2021. Colectomy rates per 100 UC patients fell from 1.47 colectomies in 2005 to 0.25 in 2021 (p=0.009). Temporal trend analysis (2005-2021) identified a significant joinpoint in colectomy rates in 2014 (p=0.009) (Figure 2).

Figure 1, Colectomy rates per 100 UC patients from 2005-2021. Joinpoint regression separated at inflection point at 2014 (dashed line).

383 patients were treated with their first advanced therapy for UC between 2005 and 2021, of whom 165 progressed to second line therapy. The annual percentage change in first line therapy was 34.7%, with joinpoints at 2013 and 2015 (p<0.001).

Figure 2, First line advanced therapy prescription rate per 100 UC patients per year between 2005-2021 stratified by agent used.

Figure 3, Second line advanced therapy prescription rate per 100 UC patients per year between 2005-2021 stratified by agent used.

The 1 and 2 year persistence on first line advanced therapy was; 44.8% and 24.1% for adalimumab, 60.7% and 54.4% for infliximab and 79.8% and 67% for vedolizumab (p=0.001) (Fig 3).

Fig 4, Persistence on first line advanced therapy.

Conclusion

This population based cohort study has shown a significant increase in advanced therapy prescription for UC. Whilst we cannot ascribe causality this has been paralleled by a significant reduction in the rate of colectomy that has been maintained in recent years.
P565 Comparison of the efficacy of adalimumab and ustekinumab for prevention of intestinal fibrosis in bio-naive Crohn's Disease patients
Authors: Biscanin A , Tomašić V , Babic F , Ćaćić P , Ogresta Kordej D , Hrabar D , Kralj D , Dorosulić Z
Published: January 2023

Background

Adalimumab (ADA) and ustekinumab (UST) are effective and efficient therapeutic options for patients with luminal Crohn's disease (CD). However, data evaluating treatment efficacy in stricturing CD are lacking. The aim of this study was to compare real-life efficacy of ADA and UST in prevention of development and/or progression of preexisting bowel stenosis in bio-naive CD patients. Secondary aim was to identify potential factors affecting treatment success.

Methods

A single-center, non interventional, retrospective chart review (January 2015 – April 2022) ofadult bio-naive CD patients treated with ADA or UST for a minimum of 6 months was performed.

Fibrotic intestinal stricture was defined as stenosis with a prestenotic small bowel or colon dilatation seen on magnetic resonance enterography or intestinal ultrasound or as a small bowel or colon obstruction impassable for an endoscope.

Continuous variables were compared using Mann-Whitney test, and categorical variables using X2 Fisher exact test when appropriate. Categorical variables were presented as numbers and valid percentages. Logistic regression was performed to determine potential predictors for stenosis development or progression.

Results

Total of 63 CD patients were included, with in ADA group (69.8%). Patients characteristics were similar in both observed groups regarding median disease duration prior to induction of biologic (57 (20-132) months on ADA, 57 (20-161) months on UST) and median treatment persistence (21 (10-38) months on ADA, 20 (14-53) on UST). Patients on UST were significantly older (ADA mean 37 y vs UST mean 51 y; p<0.05). Combotherapy was used in 35.1% of patients in ADA group.

After average of 20 months of treatment duration 9.1% people in ADA group and 5.3% in UST group developed new symptomatic bowel stenosis. At the time of biologic introduction, 4 people in ADA (9.1%) and 1 in UST group (5.3%) had preexisting bowel stenosis - out of those patients, 3 in ADA group (6.8%), had a worsening of stenosis which required treatment discontinuation. Surgery was performed in 2 patients, both in ADA group (4.5%).

Statistically significant difference wasn’t observed between ADA and UST group in stenosis development or progression (p=0.52). Combotherapy had no influence on primary aim in ADA group (p=0.59)Age, gender, biologic therapy, combotherapy as well as disease and therapy duration don't seem to be connected with stenosis development or progression

Conclusion

These real world data suggest that longterm treatment with both ADA and/or UST provide comparable efficiency for prevention of intestinal bowel fibrostenosis occurrence or progression. Larger, prospective studies should be conducted