Marc-André Bigard

Diffusion-weighted magnetic resonance without bowel preparation for detecting colonic inflammation in inflammatory bowel disease

Objective Magnetic resonance imaging (MRI) enables accurate assessment of inflammatory bowel diseases (IBD), but its main limitation is the need for bowel preparation. Diffusion-weighted imaging is feasible in Crohns disease. We evaluated the accuracy of MRI in combination with diffusion-weighted imaging (DWI-MRI) without oral or rectal preparation in assessing colonic inflammation in both ulcerative colitis and Crohns disease. Design This was an observational study of a single-centre cohort. Patients All patients who underwent DWI-MRI-colonography without bowel preparation between January 2008 and February 2010 in our centre were analysed. Results Among the 96 patients (ulcerative colitis=35; Crohns disease=61) who had DWI-MRI-colonography, 68 had concomitant endoscopy. In ulcerative colitis a segmental magnetic resonance score (MR-score-S) >1 detected endoscopic inflammation with a sensitivity and specificity of 89.47% and 86.67%, respectively (AUROC=0.920, p=0.0001). In the Crohns disease group, a MR-score-S >2 detected endoscopic inflammation in the colon with a sensitivity and specificity of 58.33% and 84.48%, respectively (AUROC=0.779, p=0.0001). The MR-score-S demonstrated better accuracy for the detection of endoscopic inflammation in the ulcerative colitis group than in the Crohns disease group (p=0.003). In ulcerative colitis, the proposed total magnetic resonance score (MR-score-T) correlated with the total modified Baron score (r=0.813, p=0.0001) and the Walmsley index (r=0.678, p<0.0001). In Crohns disease, the MR-score-T correlated with the simplified endoscopic activity score for Crohns disease (r=0.539, p=0.001) and the Crohns disease activity index (r=0.367, p=0.004). The DWI hyperintensity was a predictor of colonic endoscopic inflammation in ulcerative colitis (OR=13.26, 95% CI 3.6 to 48.93; AUROC=0.854, p=0.0001) and Crohns disease (OR=2.67, 95% CI 1.25 to 5.72; AUROC=0.702, p=0.0001). The accuracy of the DWI hyperintensity for detecting colonic inflammation was greater in ulcerative colitis than in Crohns disease (p=0.004). Conclusions DWI-MRI-colonography without bowel preparation is a reliable tool for detecting colonic inflammation in ulcerative colitis.

Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn's disease

Objective The aim of the study was to assess whether azathioprine and antitumour necrosis factor (TNF) treatment decrease the long-term need for surgery in patients with Crohns disease. Methods This was an observational study of a referral centre cohort. The cumulative incidence of the first Crohns disease-related major abdominal surgery was estimated using the Kaplan–Meier method, and independent predictors of surgery were identified using Cox proportional hazards regression with propensity scores adjustment. Receiver operating characteristic (ROC) analysis was used to identify optimal cut-offs for duration of maintenance treatments. The electronic charts of 296 incident cases of Crohns disease from Nancy University Hospital, France, diagnosed between 2000 and 2008, were reviewed through January 2010. Results The median follow-up time per patient was 57 months. Seventy-six patients (26%) underwent at least one major abdominal surgical procedure. The cumulative probabilities of the first Crohns disease-related major abdominal surgery were 6.5, 25.9 and 44.3 at 1, 5 and 9 years, respectively. In the ROC analysis, the duration of anti-TNF and azathioprine treatment had significant cut-off values (≤475 days ∼16 months and ≤45 days ∼1.5 months, respectively) with positive likelihood ratios (PLRs) of 1.52 (p<0.0001) and 1.51 (p=0.003) for the first Crohns disease-related major abdominal surgery. Using multivariate Cox proportional hazards regression analysis (after propensity score adjustment), independent positive predictors of major abdominal surgery were stricturing (HR=12.01; 95% CI 5.97 to 24.17) or penetrating (HR=10.77; 95% CI 4.87 to 23.80) disease behaviour at diagnosis, duration of anti-TNF treatment of <16 months (HR=3.86; 95% CI 1.77 to 8.45) and duration of azathioprine treatment of <1.5 months (HR=2.00; 95% CI 1.20 to 3.34). Conclusions Non-complicated inflammatory disease behaviour and long-term anti-TNF treatment are associated with a lower risk for surgery whereas azathioprine only modestly lowers this risk.

A multicenter experience with infliximab for ulcerative colitis: outcomes and predictors of response, optimization, colectomy, and hospitalization.

OBJECTIVES:The objective of this study was to evaluate short- and long-term outcomes of infliximab in ulcerative colitis (UC), including infliximab optimization, colectomy, and hospitalization.METHODS:This was a retrospective multicenter study. All adult patients who received at least one infliximab infusion for UC were included. Cumulative probabilities of event-free survival were estimated by the Kaplan–Meier method. Independent predictors were identified using binary logistic regression or Cox proportional-hazards regression, and results were expressed as odds ratios or hazard ratios (HRs), respectively.RESULTS:Between January 2000 and August 2009, 191 UC patients received infliximab therapy. Median follow-up per patient was 18 months (interquartile range=25–75th, 8–32 months). Primary non-response was noted in 42 patients (22.0%). “Hemoglobin at infliximab initiation ≤9.4 g/dl” (odds ratio=4.35; 95% confidence interval (CI)=1.81–10.42) was a positive predictor of non-response to infliximab. Infliximab optimization was required in 36 (45.0%) of 80 patients on scheduled infliximab therapy. The only predictor of infliximab optimization was “infliximab indication for acute severe colitis” (HR=2.75; 95% CI=1.23–6.12). Thirty-six patients (18.8%) underwent colectomy. Predictors of colectomy were: “no clinical response after infliximab induction” (HR=7.06; 95% CI=3.36–14.83), “C-reactive protein at infliximab initiation >10 mg/l” (HR=5.11; 95% CI=1.77–14.76), “infliximab indication for acute severe colitis” (HR=3.40; 95% CI=1.48–7.81), and “previous treatment with cyclosporine” (HR=2.53; 95% CI=1.22–5.28). Sixty-nine patients (36.1%) were hospitalized at least one time and UC-related hospitalizations rate was 29 per 100 patient-years (95% CI=24–35 per 100 patient-years). Predictors of first hospitalization were: “no clinical response after infliximab induction” (HR=3.87; 95% CI=2.29–6.53), “infliximab indication for acute severe colitis” (HR=3.13, 95% CI=1.65–5.94), “disease duration at infliximab initiation ≤50 months” (HR=2.14, 95% CI=1.25–3.66), “hemoglobin at infliximab initiation ≤11.8 g/dl” (HR=1.77; 95% CI=1.03–3.04), and “previous treatment with methotrexate” (HR=0.30; 95% CI=0.09–0.97).CONCLUSIONS:Primary non-response to infliximab was noted in one fifth of patients and increased by seven and four the risks of colectomy and hospitalization, respectively. Infliximab optimization, colectomy, and hospitalization were required in half, one fifth, and one third of patients, respectively. Infliximab indication for acute severe colitis increased by three the risks of infliximab optimization, colectomy, and UC-related hospitalization.

Long‐term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single‐centre experience

Background  Adalimumab may be effective in inducing remission in patients with mild‐to‐moderate ulcerative colitis who had secondary failure to infliximab.

Predictors of Infliximab Failure After Azathioprine Withdrawal in Crohn's Disease Treated With Combination Therapy

OBJECTIVES:Whether all Crohns disease (CD) patients should maintain long-term azathioprine treatment in combination with infliximab remains controversial. We analyzed the predictive factors of infliximab failure after azathioprine withdrawal.METHODS:This was an observational study from a single referral center. All patients with luminal CD in remission who stopped azathioprine after receiving infliximab in combination with azathioprine for at least 6 months were studied. Cumulative probabilities of infliximab failure-free survival were estimated by the Kaplan–Meier method from the date of azathioprine withdrawal to the date of infliximab failure or last known follow-up. Infliximab failure was defined by: (i) disease flare requiring shortening of the dosing interval or increasing the infliximab dose to 10 mg/kg, or switching to adalimumab; (ii) acute or delayed hypersensitivity reactions leading to infliximab discontinuation; or (iii) CD-related surgery.RESULTS:At last known follow-up, 35 out of 48 (73%) patients were infliximab failure free. The survival probabilities were 85% (±5%) at 12 months and 41% (±18%) at both 24 and 32 months. Cox proportional-hazards regression identified three predictors of infliximab failure: infliximab–azathioprine exposure duration of ⩽811 days (hazard ratio (HR)=7.46, P=0.01), C-reactive protein >5 mg/l (HR=4.79, P=0.008), and platelet count >298 109/l (HR=4.75, P=0.02).CONCLUSIONS:In CD in clinical remission under azathioprine–infliximab combination therapy, azathioprine withdrawal is associated with a high risk of relapse in patients with a duration of combination therapy of <27 months and/or the presence of biological inflammation.

Adalimumab maintenance therapy for Crohn’s disease with intolerance or lost response to infliximab: an open‐label study

Adalimumab is effective in inducing remission in patients with active Crohn’s disease who had secondary failure to infliximab therapy.

Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France.

Background: Data regarding the prevalence of hepatitis C (HCV) and hepatitis B (HBV) in inflammatory bowel disease (IBD) patients are conflicting. Methods: In all, 315 IBD (252 Crohns disease [CD] and 63 ulcerative colitis [UC]) patients were consecutively recruited between June 2005 and May 2009. Results: The median age was 33 years (interquartile range [IQR]: 24–43) and median disease duration was 5 years (IQR: 2–11). Present and/or past HBV and HCV infection was found in 2.86% of 315 patients (CD: HBsAg 0.79%, anti‐HBc 2.78%, anti‐HCV 0.79%; UC: HBsAg 1.59%, anti‐HBc 1.59%, anti‐HCV 1.59%). Effective vaccination (anti‐HBs without anti‐HBc) was present in 48.9% of 315 patients. In multivariate analysis, age at diagnosis over 31 years (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.15–0.58; P = 0.005), disease duration over 7 years (OR 0.43; 95% CI 0.23–0.83; P = 0.005), age at inclusion over 33 years (OR 0.44; 95% CI 0.20–0.94; P = 0.005), and CD (OR 0.29; 95% CI 0.15–0.58; P = 0.005) were associated with the lack of effective vaccination. Two HBsAg‐positive patients, including 1 under curative nucleoside/nucleotide analog treatment, had received 6 and 7 infliximab infusions, and 1 HCV RNA‐positive subject had been receiving corticosteroid and azathioprine therapies for 12 and 33 months, respectively. No viral reactivation occurred in these patients. Conclusions: The prevalence of HBV and HCV infection in French IBD patients is similar to that of the general population. While the ECCO recommends an effective HBV vaccination in IBD, half of the patients were not vaccinated. The nonvaccination risk factors identified in our study may allow targeted vaccination coverage. (Inflamm Bowel Dis 2009;)

Certolizumab use in pregnancy

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Nonfistulizing perianal Crohn's disease: Clinical features, epidemiology, and treatment

Nonfistulizing perianal lesions, including ulcerations, strictures, and anal carcinoma, are frequently observed in Crohns disease. Their clinical course remains poorly known. The management of these lesions is difficult because none of the treatments used is evidence-based. Ulcerations may be symptomatic in up to 85% of patients. Most ulcerations heal spontaneously but may also progress to anal stenosis or fistula/abscess. Topical treatments only improve symptoms, while complete healing can occur in patients with perianal ulcerations receiving infliximab therapy. Half of all patients with anal strictures will require permanent fecal diversion. Dilatation for symptomatic strictures should be performed on a highly selective basis in the absence of active rectal disease in order to avoid infectious complications. Anorectal strictures associated with rectal lesions should first be managed with medical therapy. Skin tags are usually painless and may hide other perianal lesions. Anal cancer is uncommon. Its treatment is similar to that recommended for anal cancer occurring in non-Crohns disease patients. After reviewing the classification, clinical features, and epidemiology of each type of nonfistulizing perianal lesion (ulceration, stricture, skin tags, and anal cancer), we discuss the efficacy of medical treatment and surgery. This review article may help physicians in decision-making when managing potentially disabling lesions.

Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experience.

Background  Adalimumab is effective in inducing clinical remission in patients with Crohn’s disease who lost response or became intolerant to infliximab.