Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study.

BACKGROUND: The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown. AIM: To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation. METHODS: We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed. RESULTS: Median vedolizumab trough levels in the overall population (n = 82) were 27 µg/mL (interquartile range, IQR 21.2-33.8 µg/mL) at week 2, 23 µg/mL (IQR 15-34.5 µg/mL) at week 6 and 10.7 µg/mL (IQR 4.6-20.4 µg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 µg/mL, P = 0.035). A cut-off trough level of 18 µg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531-0.939). A vedolizumab trough level above 18 µg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4-173.0, P = 0.01). CONCLUSION: Early therapeutic drug monitoring might improve timely detection of vedolizumab-treated patients in need for an intensified dosing regimen.

Frequency of and Factors Associated With Sexual Dysfunction in Patients With Inflammatory Bowel Disease.

BACKGROUND: Improvement of quality of life is a main objective in inflammatory bowel disease [IBD] management. Data on sexual dysfunction [SD] in IBD are scarce. This study compared rates of SD between IBD patients and healthy controls [HC], and searched for predictors of SD. METHODS: All consecutive IBD patients seen in two tertiary centres during 2 months were invited to fill an anonymous validated questionnaire on their sexual function [Female Sexual Index Function and International Index of Erectile Function]. The same questionnaires were filled by HC and by patients with irritable bowel syndrome [IBS] enrolled as a second comparative group. RESULTS: In all, 358 IBD patients filled the questionnaire [192 women]-including 238 with Crohn's disease and 120 with ulcerative colitis-and 110 HC [54 women] and 107 IBS patients [54 women]. In women, SD rates were 53.6% in IBD vs 28% in HC [p < 0.01] and 77.5% in IBS [p = 0.10] patients; in men, figures were 16.9% in IBD, 7.4% in HC [p = 0.64], and 26.4% in IBS [p = 0.60]. An erectile dysfunction [ED] was reported by 43% of IBD patients, 13% of HC [p < 0.01] and 55% of IBS patients [p = 0.60 vs IBD]. Predictors of SD and ED were social and emotional functioning, anxiety in women and depression in men. IBD activity was not associated with SD. CONCLUSIONS: In IBD, 54% of women have an SD and 43% of men an ED. These rates are significantly higher than in HC, mostly driven by psychological factors, and independent from disease severity.

Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease.

BACKGROUND: Therapeutic monoclonal anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies are associated with immune-mediated enterocolitis. The aim of this study was to provide a detailed description of this entity. METHODS: We included patients with endoscopic signs of inflammation after anti-CTLA-4 infusions for cancer treatment. Other causes of enterocolitis were excluded. Clinical, biological and endoscopic data were recorded. A single pathologist reviewed endoscopic biopsies and colectomy specimens from 27 patients. Patients with and without enterocolitis after ipilimumab-treated melanoma were compared, to identify clinical factors associated with enterocolitis. RESULTS: Thirty-nine patients with anti-CTLA-4 enterocolitis were included (ipilimumab n = 37; tremelimumab n = 2). The most frequent symptom was diarrhoea. Ten patients had extra-intestinal manifestations. Most colonoscopies showed ulcerations involving the rectum and sigmoid, 66% of patients had extensive colitis, 55% had patchy distribution and 20% had ileal inflammation. Endoscopic colonic biopsies showed acute colitis in most patients, while half of the patients had chronic duodenitis. Thirty-five patients received steroids that led to complete clinical remission in 13 patients (37%). Twelve patients required infliximab, of whom 10 (83%) responded. Six patients underwent colectomy (perforation n = 5; toxic megacolon n = 1); one of them died postoperatively. Four patients had a persistent enterocolitis at follow-up colonoscopy. Patients with enterocolitis were more frequently prescribed NSAIDs compared with patients without enterocolitis (31 vs 5%, p = 0.003). CONCLUSIONS: Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. Rapid escalation to infliximab should be advocated in patients who do not respond to steroids. Patients treated with anti-CTLA-4 should be advised to avoid NSAIDs.