Effects of discontinuing anti-tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure.

BACKGROUND & AIMS: We assessed the course of inflammatory bowel disease (IBD) among pregnant women who stopped taking anti-tumor necrosis factor (TNF) agents. We also analyzed levels of anti-TNF agents in cord blood samples. METHODS: We followed 31 pregnancies in 28 women with IBD between April 2006 and April 2011 who were treated with anti-TNF agents (18 received infliximab, and 13 received adalimumab) during pregnancy. We used enzyme-linked immunosorbent assays to measure levels of anti-TNF agents in cord blood collected from 18 newborns (12 whose mothers took infliximab, and 6 whose mothers took adalimumab). RESULTS: Among the patients taking infliximab, 12 (71%) discontinued treatment before gestational week 30; all patients remained in remission. All the patients taking adalimumab discontinued treatment before gestational week 30; two patients had relapses of IBD. There were 28 live births, 1 miscarriage among patients taking infliximab (at gestational week 6), and 2 miscarriages among patients taking adalimumab (at weeks 6 and 8); there were no congenital malformations. The mean cord blood level of infliximab was 6.4 ± 1.6 µg/mL; it was significantly lower among women who received the drug 10 weeks or less before delivery (2.8 ± 1.1 µg/mL) than those who received infliximab closer to delivery (10 ± 2.3 µg/mL; P = .02). Adalimumab was detected in 5 samples of cord blood (mean concentration, 1.7 ± 0.4 µg/mL); 1 cord blood sample from a woman who discontinued the treatment at gestational week 22 had an undetectable level of the drug. CONCLUSIONS: Discontinuation of anti-TNF therapy appears to be safe for pregnant women with quiescent IBD. However, these drugs are still detected in cord blood samples.

[Tubulo-interstitial nephritis in inflammatory bowel disease: extra-intestinal manifestation or drug toxicity?]. / Tubulo-interstitiële nefritis bij inflammatoire darmziekte: extra-intestinale manifestatie of geneesmiddeltoxiciteit?

Chronic inflammatory bowel disease (IBD) is seldom complicated by renal function disorder, but when this occurs the consequences are serious. In addition to the known effects of 5-aminosalicylates, there is also evidence that tubulo-interstitial nephritis (TIN) occurs as an extra-intestinal manifestation of IBD. A 27-year-old woman with colitis ulcerosa, developed end-stage renal insufficiency due to a mesalazine-induced TIN. She was treated by haemodialysis for two years before she underwent renal transplantation. Another patient, a 36-year-old man with Crohn's disease, developed extensive granulomatous nephritis with stable moderate renal function. After excluding other possible causes, we diagnosed an extra-intestinal manifestation of his Crohn's disease. There are no official guidelines on renal function monitoring in IBD patients, nor is there consensus in literature. We advise renal monitoring after three months of treatment with 5-aminosalicylates, followed by monitoring every year. Patients not receiving treatment should be monitored every year.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).

BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.

Autoimmune pancreatocholangitis: a series of ten patients.

BACKGROUND: During a 10-year period we observed 10 patients who suffered from an inflammatory-fibrosing disease mimicking pancreatic carcinoma and primary sclerosing cholangitis (PSC). METHODS: A review of the presenting features, the clinical course and the relevant literature. RESULTS: Ten male patients (mean age 55 years) presented with weight loss, jaundice and pruritus. Pancreatic cancer was suggested by imaging studies, which showed focal or generalized pancreatic enlargement and compression of the distal common bile duct. Cholangiography also demonstrated intrahepatic biliary stenoses consistent with sclerosing cholangitis. None had evidence of IBD. Exocrine pancreatic insufficiency was found in six cases and diabetes in four. Pancreatic histology (n=3) showed fibrosis and extensive inflammatory infiltrates. Immunosuppressive treatment was instituted in five patients. Clinical and biochemical remission occurred in three; in one other patient, previously documented intrahepatic biliary strictures had disappeared after 3 months. One patient had concomitant Sjögren's disease. The clinical features, pancreatic involvement, age at presentation, absence of IBD and response to steroids all plead against a diagnosis of "classical" PSC. The natural course of the disease was highly variable. Thirty-five comparable cases, with a largest series of three, have been reported in the literature. The disease has been associated with Sjögren's disease, retroperitoneal fibrosis and other fibrosing conditions, and may be a manifestation of a systemic fibro-inflammatory disorder. CONCLUSION: Autoimmune pancreatocholangitis is a distinct inflammatory disorder involving the pancreas and biliary tree. The disease may mimick pancreatic carcinoma and PSC and responds to immunosuppressives.

Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899].

BACKGROUND: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. METHODS: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs. RESULTS: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk. CONCLUSION: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding.