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      Faecal Calprotectin Is a Very Reliable Tool to Predict and Monitor the Risk of Relapse After Therapeutic De-escalation in Patients With Inflammatory Bowel Diseases

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          Abstract

          Aims

          To assess faecal calprotectin [Fcal] levels before and after therapeutic de-escalation, to predict clinical relapse in patients with inflammatory bowel disease [IBD].

          Methods

          From a prospectively maintained database, we enrolled 160 IBD patients [112 Crohn’s disease/48 ulcerative colitis] in clinical remission, with Fcal measured within 8 weeks before therapeutic de-escalation. Clinical relapse was defined using the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index.

          Results

          Using a receiver operating characteristic [ROC] curve, Fcal >100 µg/g was the best threshold to predict clinical relapse after therapeutic de-escalation (area under the curve [AUC] = 0.84). In multivariate analysis, clinical remission >6 months before therapeutic de-escalation (hazard ratio [HR] = 0.57 [0.33–0.99]; p = 0.044) was associated with decreased risk of relapse, whereas current steroid medication ( = 1.67[1.00–2.79]; p <0.0001) was a risk factor. Fcal >100 µg/g was predictive of clinical relapse (HR = 3.96 [2.47–6.35]; p < 0.0001) in the whole cohort but also in patients receiving anti-tumour necrosis factor [TNF] agents [n = 85 patients; p <0.0001], anti-integrins [n = 32; p = 0.003], or no biologics [n = 43; p = 0.049], or attempting to discontinue steroids [n = 37; p = 0.001]. One patient [1/98] and seven patients [7/88, 8.0%] with baseline Fcal <100 µg/g relapsed within 3 months and 6 months after therapeutic de-escalation, respectively. A total of 74 Fcal measurements were performed in 52 patients after therapeutic de-escalation. Monitoring Fcal >200 µg/g [ROC curve with AUC = 0.96] was highly predictive of clinical relapse in multivariate analysis ([HR = 31.8 [3.5–289.4], p = 0.002). Only two relapses [2/45, 4.4%] occurred within 6 months while Fcal <200 µg/g.

          Conclusions

          Fcal level is highly accurate to predict and monitor the risk of relapse after therapeutic de-escalation in IBD patients and could be used in daily practice.

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          Most cited references27

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          Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis.

          Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs.
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            The natural history of adult Crohn's disease in population-based cohorts.

            Natural history studies provide invaluable data on the disease course. First, they help define the end points for clinical trials that are designed to test drugs for the end point of disease modification in chronic disabling diseases. Natural history studies can also help to identify subsets of patients in whom the disease prognosis can be stratified according to clinical features. This comprehensive review summarizes our current knowledge of the natural history of Crohn's disease in adults as reported in population-based studies that include long-term follow-up results. We conducted a literature search of English and non-English language publications listed in the electronic databases of MEDLINE (source PUBMED, 1935 to December 2008). One-third of the patients had ileitis, colitis, or ileocolitis at the time of diagnosis. Disease location remained broadly stable over time. Up to one-third of the patients had evidence of a stricturing or penetrating intestinal complication at diagnosis, and half of all patients had experienced an intestinal complication within 20 years after diagnosis. Ten percent of the patients had prolonged clinical remission. Steroid dependency occurred in one-third of the patients, and surgery was required in one-third after initiation of steroid therapy. The annual incidence of hospitalizations was 20%. Half of the patients required surgery within 10 years after diagnosis. The risk of postoperative recurrence was 44-55% after 10 years. Crohn's disease is a disabling condition over time. The impact of changing treatment paradigms with increased use of immunosuppressants and biological agents on its natural history is poorly known.
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              Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.

              Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.
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                Author and article information

                Journal
                Journal of Crohn's and Colitis
                Oxford University Press (OUP)
                1873-9946
                1876-4479
                August 2019
                August 14 2019
                February 06 2019
                August 2019
                August 14 2019
                February 06 2019
                : 13
                : 8
                : 1012-1024
                Affiliations
                [1 ]Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
                [2 ]Université Clermont Auvergne, Inserm, CHU Clermont-Ferrand, 3iHP, Service d’Hépato-Gastro Entérologie, Clermont-Ferrand, France
                [3 ]Université Clermont Auvergne, 3iHP, Inserm U1071, M2iSH, USC-INRA 2018, Clermont-Ferrand, France
                [4 ]Department of Medicine, Queen Elizabeth Hospital, King’s Park, Hong Kong
                [5 ]Université Clermont Auvergne, CHU Clermont-Ferrand, DRCI, Unité de Biostatistiques, Clermont-Ferrand, France
                Article
                10.1093/ecco-jcc/jjz023
                6939876
                30726887
                2f5a53f8-bea1-4422-886e-4440be78fe47
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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