How are patients’ preferences for anti-TNF influenced by quality of life? A discrete choice experiment in Crohn’s disease patients

International audienc

Predictors of each quality of life dimension in Crohn’s disease patients initiating an anti-TNF treatment: differentiated effects of patient-, disease-, and treatment-related characteristics

International audienc

VALIDation of the IBD-Disk Instrument for Assessing Disability in Inflammatory Bowel Diseases in a French Cohort: The VALIDate Study

International audienceBackground and aims - Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time. Methods - From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3-12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits. Results - A total of 447 patients [71% Crohn's disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p <0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach's α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time. Conclusions - This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC

Confocal laser endomicroscopy as predictive biomarker of clinical and endoscopic efficacy of vedolizumab in ulcerative colitis: The DETECT study

International audienceAIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4β7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4β7- and TNF-expressing cells. Positive α4β7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4β7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083

Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial

International audienceAbstract Background Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis. Methods Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation. Discussion On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future. Trial registration ClinicalTrials.gov, NCT03524352 . Registered on 14 May 2018

Adalimumab staining of colonic biopsies detected by CLE and response to adalimumab at week 30.

Adalimumab staining of colonic biopsies detected by CLE and response to adalimumab at week 30.</p

Vedolizumab staining of colonic biopsies detected by CLE at inclusion and response to vedolizumab at week 22.

Vedolizumab staining of colonic biopsies detected by CLE at inclusion and response to vedolizumab at week 22.</p

DETECT study flow chart.

A total of 23 patients were screened for eligibility and 19 were enrolled in the study and received at least one dose of vedolizumab. Three patients did not meet the inclusion criteria and one patient declined its participation. All patients received vedolizumab at day 0 and week 2, 6 and 14 and were evaluated at week 22. One patient who discontinued vedolizumab between day 0 and week 22 and, who received prematurely adalimumab was considered as a failure of vedolizumab and was analyzed at week 30.</p

S2 Fig -

Absolute counts of T cells (panel A), B cells (panel B) and NK cells (panel D) as determined by flow cytometry in responders (R) and non-responders (NR) to vedolizumab at week 0 (W0) and week 22 (W22). The monocyte blood count (panel C) was measured using the Sysmex XS-800i analyzer. There was no difference of absolute counts of the different cells between responders and non-responders to vedolizumab. In responder patients, the absolute count of monocytes (panel C) decreased significantly between week 0 and 22 and monocytes were also significantly fewer at week 22 in responders compared to non-responders. α4β7 expression was analyzed by flow cytometry using a FITC-conjugated vedolizumab antibody in T cells (panel E), B cells (panel F), NK cells, monocytes (panel G) and NK cells (panel H). There was no difference between responders and non-responders to vedolizumab at week 0 before the initiation of the treatment. At week 22, the number of vedolizumab positive B cells decreased significantly in both responders and non-responders (panel F). (TIF)</p