Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Estimating the prevalence of inflammatory bowel disease in Portugal using a pharmaco-epidemiological approach.

PURPOSE: To estimate inflammatory bowel disease (IBD) prevalence in Portugal from 2003 to 2007, and to obtain disease, sex and age specific estimates. METHODS: A pharmaco-epidemiological approach based on intestinal anti-inflammatory (IAI) drugs consumption was used. Proportion of patients taking IAI drugs and mean prescribed daily dose (PDD) were estimated from a sample of 513 IBD patients. Assumptions were made about unknown parameters and sensitivity analysis performed: drug compliance (80% in base case; range 70-85%) and proportion of sulphasalazine used in IBD (52%; range 40-80%). Sex and age specific estimates were based on a proposed methodological extension and results from a nationwide (n = 5893) cross-sectional study. RESULTS: IBD prevalence increased from 86 patients per 100 000 in 2003 to 146 in 2007. Regions more affected were Lisboa and Porto (173 and 163 per 100 000 in 2007, respectively). Prevalence increased from 42 and 43 per 100 000 in 2003 to 71 and 73 in 2007, respectively for ulcerative colitis (UC) and Crohn's disease (CD). In 2007, prevalence was higher in the 40-64 age stratum for UC (99 per 100 000) and in the 17-39 stratum for CD (121). Prevalence was consistently higher in females. CONCLUSIONS: Portugal is half way between countries with the highest and lowest IBD prevalence, but is steeply making the road to the highest-level group. Despite limitations of the proposed methods, assumptions were reasonable and estimates seem to be valid. Feasibility and comparability of this methodology makes it an interesting tool for future studies on IBD epidemiology.

Inflammatory bowel disease: a patient's and caregiver's perspective.

The purpose of this study was to conduct a survey examining the impact of inflammatory bowel disease (IBD) on patients' and their caregivers' daily activities. Questionnaires were distributed to patients registered in the APDI (Portuguese Association for IBD) database and their respective caregivers in 2007. Of 422 patient respondents, 251 had Crohn's disease (CD) and 171 had ulcerative colitis (UC), with the majority of patients being women (58.1%) and aged over 40 years (37.4%). The number of disease flares experienced by IBD patients was slightly higher for patients with CD than for patients with UC (2.64 vs. 2.34), and surgery was more often required in CD patients as compared to UC patients (42.4 vs. 7%). Sixty percent (60%) of patients reported having no problems with mobility, daily activities, or personal hygiene; however, over half of all patients experienced some pain and anxiety. Adult patients and children and adolescents respectively experienced time off work or school due to their disease but caregivers were not affected in this regard. The caregivers life (N=324) was affected by anxiety, with the major concern reported as the risk of the patient developing cancer. Both IBD patients and caregivers thought that the provision of information on new drugs and contact time with a doctor would have the biggest impact on improving care. The symptoms and complications of IBD have a considerable impact on the lives of patients and their caregivers, and several actions could be taken to improve their care.

One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.

OBJECTIVE: To assess the efficacy of lamivudine treatment on hepatitis B e antigen (HBeAg) and/or hepatitis B surface antigen (HBsAg) seroconversion, on other virological and serological markers of response including hepatitis B virus (HBV) DNA and serum aminotransferases, and the safety of lamivudine treatment in hepatitis B patients. PATIENTS: This phase III open-label study evaluated the virological and biochemical response to lamivudine in 70 Portuguese patients with HBeAg positive chronic hepatitis B. Patients were treated with lamivudine 100mg once daily for 12 months. METHODS: Antiviral activity was assessed by measuring alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels at all protocol visits, and hepatitis B serology and HBV DNA were performed at baseline and at month 12 visits. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: The primary endpoint was virological response at month 12, defined as loss of detectable HBeAg from serum with a reduction of HBV DNA to undetectable levels, and this was observed in 19/69 (27.5%) of patients. Almost half of the patients were HBV DNA negative by this time. Mean ALT values decreased steadily during treatment and by 12 months 61% of patients had values within the normal range. HBeAg seroconversion (HBeAg negative, HBeAb positive) was achieved in 27.9% of patients by 12 months, although all patients remained HBsAg positive. CONCLUSION: Lamivudine was well tolerated and the incidence of adverse events was similar to those reported in previous studies. Lamivudine treatment resulted in virological and biochemical improvements in HBeAg positive chronic hepatitis B patients, with HBeAg seroconversion in one-third of patients.