Treat to Target: A Proposed New Paradigm for the Management of Crohn's Disease.

International audience: The traditional management of CD, based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of CD and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high risk patients. This review evaluates current literature on this topic and proposes a definition for the concept treating to targets for Crohn's disease

Simplifying the detection of MUTYH mutations by high resolution melting analysis

<p>Abstract</p> <p>Background</p> <p><it>MUTYH</it>-associated polyposis (MAP) is a disorder caused by bi-allelic germline <it>MUTYH </it>mutation, characterized by multiple colorectal adenomas. In order to identify mutations in <it>MUTYH </it>gene we applied High Resolution Melting (HRM) genotyping. HRM analysis is extensively employed as a scanning method for the detection of heterozygous mutations. Therefore, we applied HRM to show effectiveness in detecting homozygous mutations for these clinically important and frequent patients.</p> <p>Methods</p> <p>In this study, we analyzed phenotype and genotype data from 82 patients, with multiple (>= 10) synchronous (19/82) or metachronous (63/82) adenomas and negative <it>APC </it>study (except one case). Analysis was performed by HRM-PCR and direct sequencing, in order to identify mutations in <it>MUTYH </it>exons 7, 12 and 13, where the most prevalent mutations are located. In monoallelic mutation carriers, we evaluated entire <it>MUTYH </it>gene in search of another possible alteration. HRM-PCR was performed with strict conditions in several rounds: the first one to discriminate the heteroduplex patterns and homoduplex patterns and the next ones, in order to refine and confirm parameters. The genotypes obtained were correlated to phenotypic features (number of adenomas (synchronous or metachronous), colorectal cancer (CRC) and family history).</p> <p>Results</p> <p><it>MUTYH </it>germline mutations were found in 15.8% (13/82) of patients. The hot spots, Y179C (exon 7) and G396D (exon 13), were readily identified and other mutations were also detected. Each mutation had a reproducible melting profile by HRM, both heterozygous mutations and homozygous mutations. In our study of 82 patients, biallelic mutation is associated with being a carrier of ≥10 synchronous polyps (p = 0.05) and there is no association between biallelic mutation and CRC (p = 0.39) nor family history (p = 0.63). G338H non-pathogenic polymorphism (exon 12) was found in 23.1% (19/82) of patients. In all cases there was concordance between HRM (first and subsequent rounds) and sequencing data.</p> <p>Conclusions</p> <p>Here, we describe a screening method, HRM, for the detection of both heterozygous and homozygous mutations in the gene encoding <it>MUTYH </it>in selected samples of patients with phenotype of MAP. We refine the capabilities of HRM-PCR and apply it to a gene not yet analyzed by this tool. As clinical decisions will increasingly rely on molecular medicine, the power of identifying germline mutations must be continuously evaluated and improved.</p

Comment extrapoler le concept de treat-to-target à la rectocolite hémorragique?

International audienceL’adoption de la stratégie thérapeutique du treat-to-target s’est imposée progressivement au cours de la maladie de Crohn. Ce concept est basé sur une évaluation régulière de l’activité de la maladie à l’aide de mesures objectives de l’inflammation muqueuse et des ajustements thérapeutiques en conséquence, approche intimement liée au concept d’intervention précoce chez les patients à risque d’évolution compliquée. Ces modifications de la prise en charge de la maladie de Crohn sont les conséquences de l’inefficacité des stratégies basées sur les symptômes pour prévenir les complications de la maladie. Appartenant au même groupe des maladies inflammatoires chroniques de l’intestin, le glissement des prises en charge et des concepts entre la maladie de Crohn et la rectocolite hémorragique sont fréquents. Le concept du treat-to-target peut s’appliquer en partie à la rectocolite hémorragique mais certaines particularités doivent être prises en considération dans le suivi de cette maladie

Reply: Response to: Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlate With Rate of Infection

International audienc

Letter: wide variation in faecal calprotectin values according to the assay

International audienceSIRS, We read with great interest the paper by Yamamotoet al. recently published.1 Of note, endoscopy with biopsiesis considered as the gold standard for the diagnosisand follow-up of patients with inflammatory bowel disease(IBD) but is expensive, time-consuming, and poorlyaccepted by the patient...

Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis.

International audienceMucosal healing (MH) as a treatment target for ulcerative colitis is of growing interest because it is associated with improved clinical outcomes. However, the feasibility and probability of reaching MH in clinical practice is unknown. We therefore evaluated the feasibility of "treating to target" according to endoscopic findings to reach MH. All endoscopic outcomes of patients with ulcerative colitis followed in a single inflammatory bowel disease unit from 2011 to 2012 were reviewed and subsequent therapeutic management. Cumulative incidence of MH and histologic healing (HH) were estimated using a Kaplan-Meier method. A total of 60 patients underwent at least 2 consecutive endoscopic assessments, of whom 45 and 48 patients had endoscopic and histologic evidence of active disease, respectively. After a median follow-up of 76 weeks, 27 of 45 (60%) patients with endoscopic disease activity at baseline achieved MH and 24 (50%) of 48 patients with histologic disease activity at baseline had HH. The cumulative probabilities of MH were 26%, 52%, and 70% at 26, 52, and 76 weeks, respectively. The cumulative probabilities of HH at weeks 26, 52, and 76 from the time of initial procedure were 19%, 41%, and 57%, respectively. Any adjustment in medical therapy in case of persistent endoscopic activity was associated with both MH and HH. Repeated assessment of endoscopic disease activity with adjustment of medical therapy to the target of MH is feasible in clinical practice in patients with ulcerative colitis, and seems to be of benefit

Switch from intravenous to subcutaneous infliximab in inflammatory bowel disease: Which consequences from a pharmacokinetic perspective?

International audienceMeeting Abstract CO-06

Pathophysiology of fecal incontinence in obese patients: A prospective case-matched study of 201 patients

International audienceBackgroundObesity is an emerging risk factor for fecal incontinence (FI). The aim of this study was to characterize pathophysiologic mechanisms of FI in obese patients compared with non-obese patients in a prospective case-matched study. MethodsThe general characteristics and data of the anorectal manometry and endosonography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by a Cleveland Clinic Incontinence Score (CCIS) >4. Obesity was defined by a body mass index 30kg/m(2). Obese patients were case-matched with two age- and sex-matched non-obese patients. Key ResultsA total of 201 patients were included (67 obese matched with 134 non-obese). The CCIS, Knowles-Eccersley-Scott Symptom Constipation Score and quality of life score were comparable between obese and non-obese patients with FI. Factors significantly associated with obesity in FI patients were cholecystectomy (odds ratio [OR]=3.45 [1.19-10.32], P=.0230), irritable bowel syndrome - diarrhea (OR=2.94 [1.22-7.19], P=.0158), upper part of the anal canal resting pressure 22mmHg (OR=3.45 [1.45-8.76], P=.0045), maximum rectal tolerable volume 240mL (OR=3.14 [1.34-7.54], P=.0082), and abdominal pressure 28mmHg (OR=2.75 [1.13-7.33], P=.0248) by multivariate analysis. Conclusions & InferencesObese patients with FI had a comparable severity of FI to that of non-obese patients with FI. Regarding obesity in patients with FI, physicians should focus on stool consistency

Prise en charge des maladies inflammatoires chroniques intestinales: Mise à jour 2021

National audienceBackground: The treatment of inflammatory bowel diseases is constantly evolving through the emergence of novel molecules and treatment goals. Implementing those progresses in daily clinical practice is necessary. Methods: Thirty-one gastroenterologists practicing in France were invited to participate in a one-day consensus meeting to update previous algorithms on management of patients with Crohn's disease and ulcerative colitis for various situations. Consensus was defined as at least 66% of experts agreeing on a response. Results: All the algorithms were previously designed assuming that patients experienced a first flare of inflammatory bowel disease and are naïve of any treatment. The consensus meeting permitted to update the previous consensus algorithms through 13 clinical situations for first, second and third-line treatment of patients with Crohn's disease and ulcerative colitis. Conclusion: The changes incorporated to the algorithms provide useful guidelines to treat patients with inflammatory bowel diseases including new molecules such as vedolizumab, ustékinumab and tofacitinib and new treatment strategies. © 2021 John Libbey Eurotext. All rights reserved

Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn's disease

International audienceBACKGROUND & AIMS: Mucosal healing has been proposed as a goal for treatment because it is associated with improved clinical outcomes of patients with Crohn's disease (CD). However, little is known about the feasibility or probability of achieving mucosal healing in clinical practice. We evaluated the feasibility of treating patients to achieve mucosal healing based on endoscopic evaluation (treating to target). METHODS: We reviewed the endoscopic outcomes of 67 patients with CD who had lesions detected by endoscopy. Patients underwent 2 to 4 subsequent endoscopic evaluations at the University of California San Diego and were followed up from 2011 through 2012; data were collected on therapies and patient management. The cumulative incidences of mucosal healing and endoscopic improvement were estimated using the Kaplan-Meier method. Factors independently associated with mucosal healing were identified using a Cox proportional hazards model. RESULTS: After a median follow-up period of 62 weeks, 34 patients (50.7%) had mucosal healing and 41 patients (61.1%) had endoscopic improvement. The cumulative probabilities of mucosal healing were 12.7% and 45.0% at 24 and 52 weeks of treatment, respectively. Factors associated with mucosal healing were as follows: fewer than 26 weeks between endoscopic procedures (hazard ratio, 2.35; 95% confidence interval, 1.15-4.97; P = .035) and adjustment to medical therapy when mucosal healing was not observed (hazard ratio, 4.28; 95% confidence interval, 1.9-11.5; P = .0003). CONCLUSIONS: In an endoscopic study of patients with CD, we found that assessment of endoscopic disease activity and adjustments to medical therapy (treat to target) increase the likelihood of mucosal healing