Few prospective data are available to support the clinical relevance of mucosal healing in patients with Crohn's disease. This study examined whether complete healing, determined by endoscopy, predicts a better outcome in Crohn's disease.
One-hundred thirty-three newly diagnosed and treatment-naïve Crohn's disease patients were given either a combination of immunosuppressive therapy (azathioprine) and 3 infusions of infliximab or treatment with conventional corticosteroids. Patients given azathioprine were given repeated doses of infliximab for relapses, patients given corticosteroids were given azathioprine in cases of corticosteroid dependency and infliximab only if azathioprine failed. A representative subset of 49 patients from the initially randomized cohort underwent ileocolonoscopy after 2 years of therapy. Correlation analysis was performed between different clinical parameters including endoscopic activity (Simple Endoscopic Score) and clinical outcome 2 years after this endoscopic examination. Data were available from 46 patients 3 and 4 years after therapy began.
Complete mucosal healing, defined as a simple endoscopic score of 0 after 2 years of therapy, was the only factor that predicted sustained, steroid-free remission 3 and 4 years after therapy was initiated; it was observed in 17 of 24 patients (70.8%) vs 6 of 22 patients with lesions detected by endoscopy (27.3%, Simple Endoscopic Score >0) (P = .036; odds ratio = 4.352; 95% confidence interval, 1.10-17.220). Fifteen of 17 patients with mucosal healing at year 2 maintained in remission without further infliximab infusions during years 3 and 4 (P = .032; odds ratio = 4.883; 95% confidence interval, 1.144-20.844).
Complete mucosal healing in patients with early-stage Crohn's disease is associated with significantly higher steroid-free remission rates 4 years after therapy began.
"Endoscopic findings have a major influence on disease outcomes in both CD     and UC     when the most severe endoscopic lesions are present. More recently, treatment-induced healing of mucosal lesions has been associated with more favourable long-term IBD courses      . These observations have led to inclusion of endoscopic outcomes in more recent clinical trials as therapeutic endpoints [14,19–23]. "
[Show abstract][Hide abstract] ABSTRACT: Background
Endoscopic activity has become a therapeutic endpoint in inflammatory bowel disease. Aim of this study was to evaluate inter-observer agreement for endoscopic scores in a real-life setting.
14 gastroenterologists with experience in inflammatory bowel disease care and endoscopic scoring reviewed videos of ulcerative colitis (n = 13) and postoperative (n = 10) and luminal (n = 8) Crohn's disease. The Mayo subscore for ulcerative colitis, Rutgeerts score for postoperative Crohn's disease, Crohn's disease endoscopic index of severity (CDEIS), and the simple endoscopic score-Crohn's disease (SES-CD) for luminal Crohn's disease were calculated. A subset of five endoscopic clips were assessed by 30 general gastroenterologists without specific experience in endoscopic scores. Kappa statistics and intraclass correlation coefficients were used to measure agreement.
Mayo subscore agreement was suboptimal: kappas were 0.53 (95% confidence interval 0.47–0.56) and 0.71 (0.67–0.76) for the two groups. Rutgeerts score agreement was fair: kappas were 0.57 (0.51–0.65) and 0.67 (0.60–0.72). Agreements for CDEIS and SES-CD were good: intraclass correlation coefficients for the two groups were 0.83 (0.54–1.00) and 0.67 (0.36–0.97) for CDEIS and 0.93 (0.76–1.00) and 0.68 (0.35–0.97) for SES-CD, respectively.
The reproducibility of endoscopic scores in inflammatory bowel disease remains suboptimal, which could potentially have major effects on therapeutic choices.
"Recently, mucosal healing has been focused as a predictive marker of sustained remission irrespective of no demonstration of clinical benefit of achieving complete mucosal healing
[18,26,27]. Rutgeerts et al.
 reported the value of an endoscopic score to predict recurrent CD. "
[Show abstract][Hide abstract] ABSTRACT: Background
Early induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD.
Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn’s Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit.
The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study.
Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.
"Former studies have demonstrated that corticosteroids are not suitable for maintenance of mucosal healing , and combination therapy with thiopurines and anti-TNF-alpha antibodies is superior compared to thiopurine monotherapy in CD regarding remission rates and MH . Emerging data indicate that early use of anti-TNF-alpha antibodies lead to better long-term outcome in IBD patients by preventing mucosal damage , , , . However, results from prospective large-scale studies are still very limited. "
[Show abstract][Hide abstract] ABSTRACT: Objective
Mucosal healing (MH) is an important treatment goal in patients with inflammatory bowel disease (IBD), but factors predicting MH under medical therapy are largely unknown. In this study, we aimed to characterize predictive factors for MH in anti-TNF-alpha antibody-treated IBD patients.
We retrospectively analyzed 248 IBD patients (61.3% CD, 38.7% UC) treated with anti-TNF-alpha antibodies (infliximab and/or adalimumab) for MH, defined as macroscopic absence of inflammatory lesions (Mayo endoscopy score 0 or SES-CD score 0) in colonoscopies which were analyzed before and after initiation of an anti-TNF-alpha antibody treatment.
In patients treated with only one anti-TNF-alpha antibody (“TNF1 group”, n = 202), 56 patients (27.7%) achieved complete MH at follow-up colonoscopy (median overall follow-up time: 63 months). In a second cohort (n = 46), which comprised patients who were consecutively treated with two anti-TNF-alpha antibodies (“TNF2 group”), 13 patients (28.3%) achieved complete MH (median overall follow-up time: 64.5 months). Compared to patients without MH, CRP values at follow-up colonoscopy were significantly lower in patients with MH (TNF1 group: p = 8.35×10−5; TNF2 group: p = 0.002). Multivariate analyses confirmed CRP at follow-up colonoscopy as predictor for MH in the TNF1 group (p = 0.012). Overall need for surgery was lower in patients with MH (TNF1 group: p = 0.01; TNF2 group: p = 0.03).
We identified low serum CRP level at follow-up colonoscopy as predictor for MH, while MH was an excellent negative predictor for the need for surgery.
PLoS ONE 06/2014; 9(6):e99293. DOI:10.1371/journal.pone.0099293 · 3.23 Impact Factor
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