Prevalence of anti-TNF contraindications in Crohn's disease: A cross-sectional survey from the GETAID.

BACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn's disease, assessing each patient's potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians' preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn's disease. Physicians' choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age.

Ustekinumab is more effective than azathioprine to prevent endoscopic postoperative recurrence in Crohn's disease.

BACKGROUND: Preventing postoperative recurrence (POR) is a major concern in Crohn's disease (CD). While azathioprine is an option, no data is available on ustekinumab efficacy in this situation. AIMS: We compared the effectiveness of ustekinumab versus azathioprine in preventing endoscopic POR in CD. METHODS: We retrospectively collected data from all consecutive CD patients treated with ustekinumab after intestinal resection in 9 centers. The control group (azathioprine alone) was composed of patients who participated in a randomized controlled trial conducted in the same centers comparing azathioprine alone or in combination with curcumin. Propensity score analyses (inversed probability of treatment weighting = IPTW) were applied to compare the two groups. The primary endpoint was endoscopic POR (Rutgeerts' index ≥ i2) at 6 months. RESULTS: Overall, 32 patients were included in the ustekinumab group and 31 in the azathioprine group. The propensity score analysis was adjusted on the main risk factors (smoking, fistulizing phenotype, prior bowel resection, resection length >30 cm and ≥2 biologics before surgery) and thiopurines or ustekinumab exposure prior to surgery making the two arms comparable (∣d∣ < 0.2). After IPTW, the rate of endoscopic POR at 6 months was lower in patients treated with ustekinumab compared to azathioprine (28.0% vs. 54.5%, p = 0.029). After IPTW, the rates of i2b-endoscopic POR (Rutgeerts' index ≥ i2b) and severe endoscopic POR (Rutgeerts' index ≥ i3) were 20.8% versus 42.5% (p = 0.066) and 16.9% versus 27.9% (p = 0.24), in the ustekinumab and azathioprine groups, respectively. CONCLUSION: Ustekinumab seemed to be more effective than azathioprine in preventing POR in this cohort of CD patients.

Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn's disease.

Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-Invasive Escherichia coli (AIEC) are frequently observed in Crohn's disease (CD) patients. AIEC bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. Transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn's disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients.

Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn's Disease After Surgery in a Randomized Controlled Trial.

BACKGROUND AND AIMS: Recurrence of Crohn's disease (CD) after surgery is a major concern. Curcumin has anti-inflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy. METHODS: We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts' index score ≥i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled. RESULTS: At month 6, postoperative recurrence (Rutgeerts' index score ≥i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P = .60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts' index score ≥i3) than patients receiving placebo (26%) (P = .034). We observed a clinical recurrence of CD (CD activity index score >150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P = .80). Quality of life scores at month 6 did not differ significantly between groups (P = .80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P = .42). CONCLUSIONS: In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility. ClinicalTrials.gov no: NCT 02255370.

Comparative Acceptability and Perceived Clinical Utility of Monitoring Tools: A Nationwide Survey of Patients with Inflammatory Bowel Disease.

BACKGROUND: Objective control of intestinal inflammation during inflammatory bowel disease (IBD) is becoming the main driver for medical treatment. However, the monitoring tools-related burden remains poorly investigated. We aimed to evaluate their comparative acceptability and utility according to patients with IBD. METHODS: After a preliminary phase, the final questionnaire encompassing self-administered and physician questionnaires was prospectively and consecutively submitted to 916 patients with IBD from 20 public and private centers. Acceptability and utility visual analog scales (VAS) were expressed as median with interquartile range. RESULTS: Regarding the group of patients with Crohn's disease (n = 618), venipuncture (VAS = 9.3 [8.8-9.7]) and ultrasonography (VAS = 9.3 [8.7-9.7]) were the most acceptable tools (P < 0.0001, for each comparison), whereas rectosigmoidoscopy was the least acceptable tool (VAS = 4.4 [1.2-7.3]) (P < 0.0001, for each comparison). Wireless capsule endoscopy (VAS = 8.5 [5.2-9.3]), magnetic resonance enterocolonography (VAS = 8.0 [5.0-9.2]), and stools collection (VAS = 7.7 [4.6-9.3]) were more acceptable than colonoscopy (VAS = 6.7 [4.3-8.9]) (P < 0.0001, for each comparison). The acceptability was assessed in 298 patients with ulcerative colitis for venipuncture (VAS = 9.4 [8.8-9.7]), stools collection (VAS = 8.1 [5.7-9.4]), colonoscopy (VAS = 7.5 [4.7-9.2]), and rectosigmoidoscopy (VAS = 6.7 [2.8-9.1]); (P < 0.001 for each comparison). All monitoring tools were considered as highly useful by patients with IBD. Decreased acceptability was related to embarrassment for the collection/transport of stools (60.7%), bowel cleansing (76.3%) for colonoscopy, abdominal discomfort (51.3%) and rectal enema (36.6%) for rectosigmoidoscopy, bowel distension (48.3%) for magnetic resonance enterocolonography, and potential capsule retention (21.4%) for wireless capsule endoscopy. CONCLUSIONS: Among the IBD monitoring tools, endoscopy demonstrated the lowest acceptability supporting the development of alternative modalities. Patients' information and examination conditions should be improved to ensure proper monitoring adherence.