Impact du dosage systématique des métabolites des thiopurines dans la prise en charge des maladies inflammatoires chroniques de l'intestin

Introduction : L'intérêt du monitorage des métabolites des thiopurines dans la prise en charge des patients atteints de Maladie de Crohn (MC) et de rectocolite hémorragique (RCH) est controversé. Le but de notre étude a été d'évaluer l'impact du dosage systématique des 6-thioguanosines (6-TGN) et des 6-méthylmercapto ribonucléotides (6-MMP), sur la prise en charge des malades traités par azathioprine ou 6-mercaptopurine, en comparaison à un groupe contrôle historique. Matériel et Méthodes : A partir de Juin 2010, tous les patients traités par thiopurines (groupe d'étude) ont eu un dosage systématique des métabolites des thiopurines 8 semaines après l'introduction du traitement. Le groupe contrôle était composé de malades traités les 3 années précédentes sans autre modification de la prise en charge générale des RCH et MC et dont les modifications thérapeutiques étaient effectuées en fonction de l'efficacité et de la tolérance clinico-biologique. Les données suivantes ont été recueillies au début du traitement, à 2 et à 6 mois : activité de la maladie, tolérance clinique et biologique (lymphocytes, volume globulaire moyen et ALAT). Résultats : Le groupe d'étude comprenait 61 patients (23 RCH et 38 MC) et le groupe contrôle 58 (21 RCH et 37 MC) et étaient comparables en termes d'ancienneté, de phénotype et de modalités de traitement. Le taux de rémission complète sans corticoïde et le taux de rémission partielle à 2 mois n'étaient pas significativement différents entre le groupe d'étude (39,3% et 49,2%) et le groupe contrôle (29,3% et 60,3%). Les taux médians respectifs de 6-TGN et de 6-MMP étaient de 253 +- 215 pmol/8.108 GR (zone thérapeutique optimale 230-600 pmol/8.108 GR) et de 1732 +- 2868 pmol/8.108 GR (zone de toxicité > 11450 pmol/8.108 GR). Il n'a pas été retrouvé de corrélation entre les taux de métabolites et la réponse clinique, ni avec les lymphocytes, le VGM et les ALAT. Vingt-cinq (40,9%) patients avaient des 6-TGN en-dessous du seuil théorique d'efficacité de 230 pmol/8.108 GR, dont 23 répondeurs. Seulement 2 malades avaient des taux de 6-MMP dans la zone toxique, sans anomalie de leur bilan hépatique. Vingt-cinq patients (42,6%) du groupe étude et 22 (37,9%) du groupe contrôle ont eu une modification thérapeutique suite à la 2e visite (ns). A 6 mois, la réponse clinique n'était pas statistiquement différente (p=0,11) entre les groupes étude (76,8%) et contrôle (69,8%). Il a été noté une tendance en faveur du groupe étude pour la diminution de la dose des corticoïdes à 2 mois (dose médiane de 0 mg vs 9,5 mg ; p =0,12) et pour le délai d'introduction des anti-TNF (161 +- 61 j vs 312 +- 296 j ; p = 0,09). L'association d'allopurinol à l'azathioprine chez 3 patients du groupe étude a permis d'atteindre un taux optimal de 6-TGN et de diminuer les 6-MMP à un taux non toxique. Conclusion : Comparé à une prise en charge classique, notre étude ne permet pas de conclure à un bénéfice du dosage systématique des métabolites des thiopurines au cours des maladies inflammatoires de l'intestin, notamment en termes de gain d'efficacité. Elle suggère toutefois que cette stratégie permet de décider des modifications thérapeutiques plus rapidement en cas de réponse incomplète et elle permet également d'optimiser le traitement chez des malades ayant un métabolisme particulier des thiopurines.POITIERS-SCD-Bib. électronique (861949901) / SudocSudocFranceF

Early enteral vs. oral nutrition after Whipple procedure: Study protocol for a multicentric randomized controlled trial (NUTRIWHI trial).

Malnutrition has been shown to be a risk factor for postoperative complications after pancreatoduodenectomy (PD). In addition, patients needing a PD, such as patients with pancreatic cancer or chronic pancreatitis, often are malnourished. The best route of postoperative nutrition after PD remains unknown. The aim of this randomized controlled trial is to evaluate if early postoperative enteral nutrition can decrease complications after PD compared to oral nutrition. This multicenter, open-label, randomized controlled trial will include 128 patients undergoing PD with a nutritional risk screening ≥3. Patients will be randomized 1:1 using variable block randomization stratified by center to receive either early enteral nutrition (intervention group) or oral nutrition (control group) after PD. Patients in the intervention group will receive enteral nutrition since the first night of the operation (250 ml/12 h), and enteral nutrition will be increased daily if tolerated until 1000 ml/12 h. The primary outcome will be the Comprehensive Complication Index (CCI) at 90 days after PD. This study with its multicentric and randomized design will permit to establish if early postoperative enteral nutrition after PD improves postoperative outcomes compared to oral nutrition in malnourished patients. https://clinicaltrials.gov/(NCT05042882) Registration date: September 2021

How are patients’ preferences for anti-TNF influenced by quality of life? A discrete choice experiment in Crohn’s disease patients

International audienc

Predictors of each quality of life dimension in Crohn’s disease patients initiating an anti-TNF treatment: differentiated effects of patient-, disease-, and treatment-related characteristics

International audienc

Indications de l’autogreffe de cellules hématopoïétiques dans la Maladie de Crohn : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire

International audienceCrohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up

Diagnostic Accuracy of a Noninvasive Test for Detection of Helicobacter pylori and Resistance to Clarithromycin in Stool by the Amplidiag H. pylori+ClariR Real-Time PCR Assay

International audienceThe noninvasive detection of Helicobacter pylori and its resistance to clarithromycin could revolutionize the management of H. pylori-infected patients by tailoring eradication treatment without any need for endoscopy when histology is not necessary. Several real-time PCR tests performed on stools have been proposed, but their performances were either poor or they were tested on too few patients to be properly evaluated. We conducted a prospective, multicenter study including 1,200 adult patients who were addressed for gastroduodenal endoscopy with gastric biopsies and who were naive for eradication treatment in order to evaluate the performance of the Amplidiag H. pyloriϩClariR assay recently developed by Mobidiag (Espoo, Finland). The results of the Amplidiag H. pyloriϩClariR assay performed on DNA from stools (automatic extraction with the EasyMag system [bioMérieux]) were compared with those of culture/Etest and quadruplex real-time PCRs performed on two gastric biopsy samples (from the antrum and corpus) to detect the H. pylori glmM gene and mutations in the 23S rRNA genes conferring clarithromycin resistance. The sensitivity and specificity of the detection of H. pylori were 96.3% (95% confidence interval [CI], 92 to 98%) and 98.7% (95% CI, 97 to 99%), respectively. The positive and negative predictive values were evaluated to be 92.2% (95% CI, 92 to 98%) and 99.3% (95% CI, 98 to 99%), respectively. In this cohort, 160 patients (14.7%) were found to be infected (positive by culture and/or PCR). The sensitivity and specificity for detecting resistance to clarithromycin were 100% (95% CI, 88 to 100%) and 98.4% (95% CI, 94 to 99%), respectively

Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID.

Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease. To assess the impact of radiotherapy on IBD course. A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow-up. Sixty-one patients (32 women, mean age 59 years), with 467 patient semesters of follow-up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S + 1 to S + 3 (P = 0.15 vs S-4 to S-1) and 16% (10-25) from S + 4 to S + 6 (P = 0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare. Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period

Prevalence of anti-TNF contraindications in Crohn’s disease: A cross-sectional survey from the GETAID

International audienceBACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn’s disease, assessing each patient’s potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians’ preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn’s disease. Physicians’ choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age