Introduction

Inflammatory bowel disease (IBD) is a chronic disease usually diagnosed in early adulthood and characterized by unpredictable flare-ups and debilitating symptoms that can interfere with the patient's ability to work and perform daily activities. In fact, since work disability is difficult to quantify, several scores have been developed for this purpose. The Work Ability Index (WAI) is a validated practical tool to measure the work capacity of patients.
The objective of this study was to assess work performance in patients followed for IBD, using the WAI psychometric tool, and to identify predictive factors of work disability.

Aims & Methods

We conducted a cross-sectional study including patients followed for IBD and exercising a professional activity, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. Quality of life was assessed by the IBDQ questionnairy.
Work capacity was assessed using the WAI which classified work performance into four categories: poor (score between 7 and 27), moderate (28-36), good (37-43) and excellent (44-49).
In order to determine the factors of disability at work, we divided our patients into two groups according to the WAI:
- Patients with work disability: WAI between 7 and 27.
- Patient with retained ability at work: WAI between 28 and 49.

Results

A total of 45 patients were included: 80% had Crohn disease (CD) and 20% had ulcerative colitis (UC). The mean age was 44 ± 12 years [20–72], the sex-ratio M/F was 0.73, and the mean of follow-up time was 9 years [1-18]. The average number of working hours per week was 38.8 ± 11 hours [9-60]. The mean absenteeism during the last twelve months was 49.6 days [0–240]. The mean WAI value was 32.6, which corresponds to a moderate work performance. Assessment of work performance according to the WAI questionnaire showed that 38% of patients (n=17) had poor work ability, 24% (n=11) moderate work ability, 34% (n=15) good work ability and only two patients (4%) had an excellent work ability.
In univariate study, the work disability was more important in workers (p=0.008), employees in private or liberal sector (p=0.017), workers with atypical schedules (p=0.034) and in case of a professional seniority higher than 16.5 years (p=0.009). Patient-related factors were advanced age, low socio-economic conditions and low educational level. Disease-related factors were stricturing phenotype of CD, extensive UC, moderate to severe disease activity, presence of extra-intestinal manifestations (EIM) and corticotherapy.
In multivariate analysis, independent predictive factors of work disability among IBD patients were:

Furthermore, the assessment of health-related quality of life by the IBDQ questionnairy, showed a mean IBDQ value of 160.8 which corresponds to a moderate score relating a quality of life; 224 being the maximum score obtainable reflecting an optimal quality of life. In the analytical study and using Spearman's test, a statistically significant correlation was found between the WAI and IBDQ with a p-value <0.0001 and a correlation coefficient r=0.7, reflecting the impact of working life on quality of life.

Conclusion

According to our study, IBD would cause work disability in 38% of cases. Moderate to severe disease activity and the presence of osteoarticular EIM were both identified as independent predictors of work disability. Thus, the WAI can be used as a screening tool to identify the need for rehabilitation.

Introduction

Most current approaches for therapy for Inflammatory Bowel Disease (IBD) focus on inhibition of excessive inflammation. However, with clinical remission rates for IBD plateauing, new approaches, are needed. The protease, Activated Protein C (APC), can exert a broad range of cytoprotective actions including inhibition of inflammation, stabilization of endothelial and epithelial barriers and suppression of apoptosis. APC shows therapeutic effects in various inflammatory diseases, and its cytoprotective functions often require biased cleavage of protease-activated receptor (PAR)1 and PAR3. Biparetide is a bivalent PAR1:PAR3-derived peptide formed by covalent linkage of PAR1-residues 47-55 to PAR3-residues 51-65 via a 10-mer oligo-Gly peptide. Biparetide in vitro mimics APC’s anti-inflammatory activity.

Aims & Methods

Aim: Our objective was to assess the in vivo therapeutic benefits of intrarectal and intraperitoneal administration of biparetide in a murine preclinical 40kDa dextran sulfate sodium (DSS) model of colitis.
Methods: Eight-week-old female C57Bl/6N mice were given 2% (weight/volume) DSS in drinking water for three 7-day cycles followed by 7 days of regular drinking water to induce colitis. Both biparetide (1, 10 and 50 mg/kg) and scrambled biparetide (peptide with randomized amino acid sequence) were given daily from day 18 to day 41 by concomitant intrarectal (half volume) and intraperitoneal (IP) injection (half volume). Anti-TNFa was administered IP 15mg/kg 3 times per week from day 18 to day 41. Prednisolone was administered IP (1mg/kg) once daily from day 18 to day 42. Control groups included healthy mice and DSS-treated animals receiving only vehicle. Colitis severity was monitored using a disease activity score (DAI) based on daily evaluation of weight, stool consistency, and presence of blood; at study end, endoscopic scoring was performed. Colon length and weight were measured, and histological analysis on formalin-fixed paraffin sections was performed by a blinded pathologist.

Results

DSS effectively induced chronic colitis. Biparetide dose-dependently reduced body weight loss compared to vehicle-dosed DSS-treated mice from day 24 (p<0.01). Biparetide at both 10 and 50 mg/kg significantly improved body weight loss compared to prednisolone (p<0.01) and anti-TNF-a from day 31 (p<0.01), and it was associated with a dose-dependent, significant reduction in DAI score compared with vehicle-dosed DSS-treated mice, e.g., from day 24 (for 10 mg/kg, p<0.01). Biparetide significantly reduced DAI compared with prednisolone (p<0.01) and reduced DAI similar to anti-TNF-a. The peptide’s protective effects against chronic colitis observed at both 10 and 50 mg/kg were accompanied by improvements in colon length shortening and in colon weight/length ratio (p<0.01), with effects comparable to anti-TNF-a. Amelioration of histological and endoscopic parameters of colitis was seen with anti-TNF-a and biparetide (10 and 50mg/kg) treatments.

Conclusion

In this DSS-induced colitis model, biparetide gave dose-dependent improvement in clinical signs and symptoms, reducing body weight loss and improving DAI score. These significant improvements were seen at 10mg/kg and 50mg/kg peptide. Similar improvements were observed during endoscopy and upon histological assessment. Here we demonstrate proof of concept that biparetide is a novel anti-inflammatory peptide that mimics APC’s previously reported in vivo benefits for DSS-induced colitis. Moreover, these data suggest that biparetide merits further evaluation for clinical translation for inflammatory pathologies.

Introduction

Data on the long-term benefit of transmural healing (TH) are scarce in children.

Aims & Methods

We investigated the outcomes of pediatric Crohn's disease (CD) patients with TH comparing them to those with mucosal healing (MH) and with “no healing”.
We conducted a prospective, single-center, observational study conducted at the Pediatric Gastroenterology Unit of Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy within a 3-month interval were consecutively enrolled. TH was defined as the complete healing of both the mucosa at endoscopy and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months number disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications were collected.

Results

93 children were included (mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. The risk of any unfavorable outcome was lower in both TH and MH patients compared to NH (Log Rank p<0.0001 and p=0.002). Children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p<0.0001 and p=0.0002, respectively) compared to NH. TH and MH patients were comparable for all the outcomes evaluated.

Conclusion

Achieving TH in pediatric CD is associated with better outcomes, although the additional benefit over MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.

Introduction

With the wider availability of non-TNFi treatments in Ulcerative Colitis (UC), the long-established treatment approach to cycle through two TNFi treatments (such as adalimumab and infliximab) is changing.

Aims & Methods

Objectives: The purpose of this study was to evaluate to what extent TNFi cycling is occurring in the EU5 management of UC, and how this has changed over the last 3 years. More specifically, the data is used to demonstrate which types of patients are likely to cycle through 2 TNFi products, and which are likely to be prescribed a non TNFi after one TNFi treatment choice.
Methodology: In Q3 of 2023, 205 gastroenterologists from France, Italy, Germany, Spain, and the UK contributed 1430 anonymous patient record forms for individuals receiving advanced therapy for UC. All the forms were collected through the Therapy Watch IBD (UC and Crohn’s) survey by Research Partnership. The survey has been conducted with similar numbers of gastroenterologists for 3 years at regular intervals. Informed consent from physicians was obtained. Where relevant, statistical comparisons were performed using a pairwise z-test.

Results

UC patients who require an advanced treatment (biologic or JAKi) are most likely to be prescribed a TNFi first-line. From our Q3 23 data, 81% of EU5 UC patients received a TNFi (most commonly adalimumab or infliximab) as first-line. The integrin blocker vedolizumab, IL12/23 inhibitors (such as ustekinumab) and JAK inhibitors are more likely to be prescribed at 2^nd or 3^rd+ line; at 2^nd line, TNFi were prescribed to 37% of patients.
In Q3 23, of the 485 UC patients who were currently on their 2^nd line of advanced treatment, 32% had a TNFi in both 1^st and 2^nd line (i.e. cycling TNFi) and 59% had a TNFi in 1^st line and a non TNFi in their 2^nd line of treatment. In Q1 21, 41% were cycling TNFi, and 50% were not. This represents a statistically significant reduction in TNFi cycling between Q1 21 and Q3 23 (p<0.05).
Certain patient characteristics are more prevalent amongst patients who switch to a non TNFi at 2^nd line, compared with those who cycle to a second TNFi, as follows (all represent a statistically significant difference, p<0.05):

• More likely to be younger (51% under 40, compared with 41% among TNFi cyclers)
• Less likely to have any comorbidities (44% no comorbidities, compared with 27% among TNFi cyclers)
• More likely to have blood in stool and bowel incontinence (45% compared with 20% among TNFi cyclers)
• More likely to have an increasing rate of UC flares (29% compared with 15% among TNFi cyclers).

Conclusion

Our findings confirm that there has been a statistically significant reduction in TNFi cycling over the past 3 years, with an increase in the proportion of UC patients who are prescribed a non TNFi in 2^nd line. TNFis remain the main 1^st line advanced treatment choice for UC.
At this point, our data suggests that physicians are making decisions between TNFi cycling and switching directly to a non-TNFi, based on certain patient characteristics or disease status.

References

Data from Therapy Watch IBD survey (UC and Crohn's) conducted by Research Partnership.