Systematic review with meta-analysis: Anti-TNF therapy in refractory pouchitis and Crohn's disease-like complications of the pouch after ileal pouch-anal anastomosis following colectomy for ulcerative colitis

International audienceBackground: Inflammatory complications including chronic refractory pouchitis and Crohn's disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch. Methods: We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95% CI[5-10] and 12 months 95% CI[12-18.5], respectively. Results: We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95% CI [0.37-0.63]; I-2 = 0.57) and 0.52 (95% CI[0.39-0.65]; I-2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95% CI[0.5-0.77]; I-2 = 0.18), compared to refractory pouchitis 0.10 (95% CI [0.00-0.35]; I-2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95% CI[0.43-0.71]; I-2 = 0.32) and 0.37 (95% CI [0.14-0.62]; I-2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected. Conclusion: Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials

Diffusion-weighted magnetic resonance enterocolonography before treatment predicts remission after anti-TNF therapy in Crohn's disease

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Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

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Diffusion-weighted magnetic resonance enterocolonography in predicting remission after anti-TNF induction therapy in Crohn's disease

International audienceBackground: Diffusion-weighted magnetic resonance entero-colonography (DW-MREC) with no rectal distension and with no bowel cleansing is accurate to assess inflammatory activity in ileocolonic Crohn's disease (CD). Aim: To study DW-MREC parameters as predictors of remission (CDAI 42.5 (OR = 5.11, 95% CI [1.03-25.37]), reflecting high inflammatory activity, were predictive of remission at week 12. Conclusions: DW-MREC using quantitative parameters i.e. ADC, is useful in detecting and assessing inflammatory activity but also to predict efficacy of anti-TNF induction therapy in CD

Fecal Matrix Metalloprotease-9 and Lipocalin-2 as Biomarkers in Detecting Endoscopic Activity in Patients With Inflammatory Bowel Diseases

International audienceBackground:Fecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBD).Goals:We aimed to evaluate the accuracy of fecal matrix metalloprotease-9 (MMP-9) and fecal lipocalin-2 (LCN-2) compared with calprotectin in detecting endoscopic activity in IBDStudy:Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) in Crohn's disease (CD) patients or Mayo endoscopic subscore calculation for ulcerative colitis (UC) patients, and stool collection. Fecal calprotectin was measured using quantitative immunochromatographic testing. Fecal MMP-9 and LCN-2 was quantified by enzyme-linked immunosorbent assay. MMP-9 and LCN-2 thresholds were determined using receiver operating curves.Results:In 54 CD patients, fecal calprotectin, MMP-9 and LCN-2 correlated with CDEIS and were significantly increased in patients with endoscopic ulcerations. MMP-9 >350 ng/g detected endoscopic ulceration in CD with a sensitivity of 90.0% and a specificity of 63.6%, compared with fecal calprotectin >250 g/g (sensitivity=90.5% and specificity=59.1%). Fecal LCN-2 demonstrated lower performances than the 2 other biomarkers (sensitivity=85.7% and specificity=45.5%).In 32 UC patients, fecal MMP-9, LCN-2, and calprotectin levels were significantly increased in patients with endoscopic activity. In UC patients, fecal MMP-9 >900 ng/g had the best efficacy to detect endoscopic activity (sensitivity=91.0% and specificity=80.0%, compared with fecal calprotectin >250 g/g (sensitivity=86.4% and specificity=80.0%) and LCN-2 >6700 ng/g (sensitivity=82.0% and specificity=80.0%).Conclusions:Fecal MMP-9 is a reliable biomarker in detecting endoscopic activity in both UC and CD patients

Development and validation of a score to assess transmural healing and response in patients with Crohn’s disease

International audienceBackground and aims: As transmural healing (TH) could be the best therapeutic target in Crohn's disease (CD), we aimed to build and validate a score to assess TH and transmural response (TR), and to confirm their association with favorable CD outcomes.Methods: DEVISE-CD project encompassed two retrospective cohorts (274 and 224 CD patients for development and validation phase, retrospectively) and one multicenter prospective validation cohort (N=46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary endpoints were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin < 250 (CFREM) at one year for retrospective and prospective validation cohorts, respectively.Results: Edema, ulcer, contrast enhancement, diffusion-weighted hyperintensity, fat wrapping, bowel thickening (>3 mm), and enlarged lymph nodes were associated to higher risk of bowel damage progression (p<0.01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (p<0.0001). Bowel thickness had the highest sensitivity to change after treatment (SMD=0.30±1.0)(p=0.001). C-score was calculated as 0.2x(bowel thickness-3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score<0.5) (HR=0.28[0.13-0.63],p=0.002; aHR=0.15[0.04-0.53], p=0.003), TR50 (50%-decrease of C-score)(HR=0.30[0.15-0.63], p=0.001; aHR = 0.36[0.14-0.88], p=0.025) or TR25(25%-decrease of C-score)(HR=0.37[0.19-0.71], p=0.003; aHR=0.46[0.23-0.94], p=0.034) prevented bowel damage progression in development and validation cohorts, respectively. In the prospective validation cohort, achieving TH (OR=4.6[1.3-15.6], p=0.016), TR50 (OR=6.9[1.8-26.0], p=0.008) or TR25 (OR=6.0[1.6-22.3], p=0.008) after 12 weeks of anti-TNF therapy led to higher rate of CFREM at one year.Conclusion: C-score is a validated, reliable and easy-to-use tool to assess TH and TR in CD patients

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease

International audienceAIM: to investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95% CI: 0.25-0.66, p < 0.001) and surgical postoperative recurrence (HR = 0.30, 95% CI: 0.13-0.70, p = 0.006). CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation

Endoscopy-based management within the first year after surgery decreases the risk of clinical and surgical postoperative recurrences in Crohn's disease

Endoscopy-based management within the first year after surgery decreases the risk of clinical and surgical postoperative recurrences in Crohn's disease. 11. Congress of European Crohn's and Colitis Organisatio

Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy

International audienceBackground - Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. Aims - We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. Methods - All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index  +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). Conclusion - Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD