The use of azathioprine in Crohn's disease during pregnancy and in the post-operative setting: a worldwide survey of experts.

BACKGROUND: Although thiopurines are considered safe in humans, they are still pregnancy FDA category D drugs. Prevention of post-operative recurrence is a challenge in clinical practice in Crohn's disease. The European Crohn's and Colitis Organisation consensus states that thiopurines should be considered in high-risk patients. AIM: To perform a worldwide survey for evaluating the extent to which gastroenterologists who are experts in the field of IBD are utilising thiopurines during pregnancy and in the post-operative setting in Crohn's disease. METHODS: This was a Web-based cross-sectional, statement-based survey, which was conducted among experts who have published at least once in the field of thiopurines in IBD. RESULTS: Between 20 December 2009 and 9 April 2010, 175 questionnaires were received. The median number of IBD patients per physician per year was 400 (IQR 25-75th, 188-600) and the total number of IBD patients followed by all responders was 82,379. In a pregnant woman with a history of severe Crohn's disease in clinical remission after 1 year on azathioprine, 89% of experts usually continue azathioprine until delivery and 9% of physicians never administer azathioprine during pregnancy. After ileocecal resection for Crohn's disease, 39% of physicians initiate azathioprine only in high-risk patients, 28% of practitioners prescribe azathioprine according to endoscopic evaluation, 20% of gastroenterologists systematically initiate azathioprine and 13% have a different attitude. CONCLUSIONS: Almost 9 of 10 physicians continue azathioprine throughout pregnancy. About 7 of 10 physicians prescribe azathioprine in the post-operative setting according to the European Crohn's and Colitis Organisation recommendations, whereas one-fifth of practitioners systematically initiate azathioprine after surgery.

Additional benefit of procalcitonin to C-reactive protein to assess disease activity and severity in Crohn's disease.

BACKGROUND: Serum procalcitonin level may reflect non-infectious inflammation. AIM: To assess the correlation of serum procalcitonin level with clinical, biological, endoscopic and radiological markers of disease activity in inflammatory bowel diseases (IBD), and to evaluate the additional diagnostic benefit of measuring serum procalcitonin level to that of C-reactive protein (CRP) for disease activity appraisal. METHODS: We performed a prospective observational study. Spearman's rank correlation and receiver operating characteristic analysis were used to evaluate correlation and diagnostic accuracy respectively. RESULTS: In Crohn's disease (CD) (n = 30), serum procalcitonin level was strongly correlated with clinical, biological, endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level >0.14 µg/L demonstrated a high accuracy for detecting severe disease (Sensitivity = 100%; Specificity = 96%; AUROC = 0.963; P = 0.0001). The diagnostic accuracy of the 'serum procalcitonin level-CRP strategy' (CRP >5 mg/L and serum procalcitonin level >0.05 µg/L) was significantly superior to that of CRP alone for diagnosing severe CD (AUROC = 0.783 vs. 0.674; P = 0.01). In ulcerative colitis (UC) (n = 27), serum procalcitonin level was correlated with CRP and with endoscopic and radiological disease activity markers. CONCLUSIONS: In CD, the serum procalcitonin level was correlated with all disease activity markers and a cut-off of 0.14 µg/L could distinguish severe forms of the disease. The 'serum procalcitonin level-CRP strategy' was superior to CRP alone for diagnosing active or severe CD.

Inflammatory bowel disease and hepatitis B and C.

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey.

BACKGROUND: Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain. AIM: To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD). METHODS: A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond. RESULTS: A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy. CONCLUSIONS: The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD.

Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximab.

BACKGROUND: In Crohn's disease, anal ulcers and stricture can be disabling. AIM: To evaluate long-term outcome of non-fistulizing perianal Crohn's disease under infliximab. METHODS: The medical records of 99 patients with non-fistulizing perianal Crohn's disease at first infliximab infusion were reviewed. Complete responses (ulcer healing or stricture regression) after induction infliximab therapy and at the maximal follow-up were assessed. RESULTS: Ninety-four patients (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal fistulas at first infliximab infusion. After infliximab induction therapy, 40/94 (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with fistulas had a complete response. Eight patients were lost to follow-up. After a median follow-up of 175 weeks (range, 13-459), complete response rates for ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8% (20/31) respectively. Long-term response for cavitating ulcer was positively associated with concomitant immunosuppressant use (P = 0.017) and older age (P = 0.049). Among the 12 patients with complete regression of stricture, 6 patients also had anal dilatation. Complete response was associated with perianal pain relief and disappearance of soiling. Three patients with ulcers developed an anal abscess. CONCLUSIONS: Infliximab therapy may be effective in inducing and maintaining response for ulcers.

TNF antagonists in the treatment of inflammatory bowel disease: results of a survey of gastroenterologists in the French region of Lorraine.

BACKGROUND AND OBJECTIVE: We conducted a survey of nonacademic gastroenterologists to evaluate the use of tumor necrosis factor (TNF) antagonists in inflammatory bowel disease (IBD). METHODS: A total of 100 questionnaires were sent by mail to a representative sample of gastroenterologists practicing in the French region of Lorraine. RESULTS: Forty-six practitioners responded to the survey, of whom 95.5% prescribed scheduled infliximab treatment. After 6 months of infliximab in combination with azathioprine, 55% then prescribed infliximab as monotherapy. A complete pretherapeutic assessment was performed by only one fourth of the gastroenterologists. When the PPD skin test measured 7 mm, nearly half of the physicians introduced anti-TNF therapy without chemoprophylaxis (versus only 2.4% when the diameter was 11 mm). In the event of quiescent Crohn's disease (CD) after 1 year of anti-TNF treatment, 35.7% stopped the drug. In refractory CD, 72.7% prescribed infliximab as the first-line therapy (versus 27.3% who used adalimumab). In patients with urinary tract infection, 44.2% initiated antibiotics and delayed anti-TNF treatment, while 46.5% initiated anti-TNF therapy along with antibiotic therapy. CONCLUSION: This study is the first survey upon the use of TNF antagonists by nonacademic gastroenterologists, and the findings suggest that physicians using these drugs may require more information about the pretherapeutic assessment and management of the infectious risk.

Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experience.

BACKGROUND: Adalimumab is effective in inducing clinical remission in patients with Crohn's disease who lost response or became intolerant to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab as a second line therapy in luminal and fistulizing Crohn's disease. METHODS: We report our single-centre experience in 53 patients. We evaluated maintenance of clinical response defined as the absence of adverse events leading to drug withdrawal, no major abdominal surgery and no loss of clinical response in initial responders. Major abdominal surgery, steroid sparing, complete fistula closure and safety were also assessed. RESULTS: The probability of maintaining clinical response was 77.2%, 67.8% and 50.8% at 26, 52 and 130 weeks respectively. The probability of remaining major abdominal surgery-free was 82.3% at 26, 52 and 130 weeks. Complete fistula closure occurred in six of 10 patients, and eight of 10 patients were able to taper steroid therapy. Adverse events occurred in 31 patients (58.5%) leading to adalimumab withdrawal in nine patients (17%). CONCLUSION: Adalimumab therapy may be effective in the long term in both luminal and fistulizing Crohn's disease in infliximab-failure patients, half of patients maintaining clinical response and potentially avoiding major abdominal surgery in 80% of cases.

Interaction of ribavirin with azathioprine metabolism potentially induces myelosuppression.

BACKGROUND: The interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity, remains unexplored. AIM: To underline the interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity. METHODS: The medical records of eight patients who developed severe pancytopenia following concomitant use of azathioprine and ribavirin were retrospectively reviewed. RESULTS: Bone marrow suppression reached nadir after a mean interval of 4.6 +/- 1.6 weeks following HCV therapy initiation in seven patients. At the time of pancytopenia, the mean platelet count was 69.75 +/- 82.8 x 10(-3)/mm(3), mean haemoglobin level 7.75 +/- 1.3 g/dL and mean neutrophil count 0.45 +/- 0.26 x 10(-3)/mm(3). All patients had normal thiopurine methyltransferase genotype. In two patients, a prospective monitoring of azathioprine metabolites was available. Myelotoxicity was accompanied by elevated total methylated metabolite levels (16,500 and 15,000 pmol/8 x 10(8) erythrocytes) with a concomitant decrease in 6-tioguanine nucleotide levels; 1 month after azathioprine, pegylated interferon alfa and ribavirin were discontinued and full blood count returned to normal in both patients. No haematological toxicity occurred after the reintroduction of peginterferon plus ribarivin or azathioprine alone in eight patients. CONCLUSION: Collectively, the benefit/risk ratio favours avoidance of inosine monophosphate dehydrogenase inhibitors in purine analogue-treated patients with normal thiopurine methyltransferase activity, a situation frequently encountered in clinical practice.

[Digestive obstruction: an unusual complication of hereditary multiple exostoses]. / Obstruction digestive : une complication exceptionnelle d'une maladie exostosante.

Hereditary multiple exostoses is an autosomal dominant bone disorder characterized by multiple cartilaginous tumors growing outward from metaphyses of long bones. These tumors are usually located in long bones of the limbs. Exostosis also called osteochondroma can cause many complications, the most serious being malignant transformation as chondrosarcoma. We report a rare phenotype of this disease in a young male patient who presents digestive symptoms caused by a voluminous degenerated lumbar exostosis with anterior abdominal development.