Use of Topical Tacrolimus and Topical Pimecrolimus in Four European Countries: A Multicentre Database Cohort Study.

BACKGROUND: Despite the concerns about a potential increased risk of skin cancer and lymphoma with the use of topical tacrolimus and pimecrolimus, no population-based studies have given an overview of the use of these drugs in Europe. OBJECTIVE: To assess the use of topical tacrolimus and pimecrolimus in children and adults in Europe. METHODS: Multicentre database cohort study comprising data from the Netherlands, Denmark, Sweden and the UK. We analysed users of topical tacrolimus and pimecrolimus starting from the date of first availability (between 2002 and 2003) or start establishment of the prescription database in Sweden (2006) through 2011. Use was assessed separately for children (≤ 18 years) and adults. RESULTS: 32,052 children and 104,902 adults were treated with topical tacrolimus, and 32,125 children and 58,280 adults were treated with topical pimecrolimus. The number of users increased rapidly after first availability, especially for topical tacrolimus. Topical tacrolimus was more frequently used in all countries except Denmark. For both drugs, there was a decrease in users after 2004 in the Netherlands and Denmark and after 2005 in the UK, especially among children. This decrease was largest in Denmark. The decrease in the number of users was temporary for topical tacrolimus, while use remained relatively low for topical pimecrolimus. CONCLUSIONS: The number of topical tacrolimus and pimecrolimus users increased rapidly after regulatory approval. A transient reduction in topical tacrolimus use and a persistent reduction in topical pimecrolimus use was seen after 2004 in the Netherlands and Denmark and after 2005 in the UK.

Palivizumab Exposure and the Risk of Atopic Dermatitis, Asthma and Allergic Rhinoconjunctivitis: A Cross-National, Population-Based Cohort Study.

BACKGROUND: Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus. It is prescribed to children at high risk for severe infection with respiratory syncytial virus. However, little is known about the risk of the immune-mediated diseases atopic dermatitis, asthma, and allergic rhinoconjunctivitis after palivizumab exposure. AIM: Our objective was to investigate whether exposure to palivizumab was associated with atopic dermatitis, asthma, or allergic rhinoconjunctivitis in childhood. METHODS: This was a cross-national population-based cohort study including data from 769,523 Danish children born 1 January 1999-31 December 2010 and 581,742 Swedish children born 1 July 2005-31 December 2010. Since palivizumab is only indicated for children at the highest risk, sub-cohorts of preterm children, children with bronchopulmonary dysplasia, and children with hemodynamic significant heart disease were defined. RESULTS: Of the 1,351,265 children included, 1192 (0.09%) were exposed to palivizumab. An increased risk of asthma after palivizumab exposure was observed in the total birth cohort (hazard ratio [HR] 1.49; 95% confidence interval [CI] 1.32-1.68) and in the sub-cohort of preterm children (HR 1.24; 95% CI 1.07-1.44). However, post hoc analyses using the propensity score to balance confounding factors found no increased risk of asthma in preterm children (HR 0.91; 95% CI 0.56-1.48). No increased risks of atopic dermatitis (HR 1.18; 95% CI 0.94-1.48) or allergic rhinoconjunctivitis (HR 1.14; 95% CI 0.92-1.42) were observed. CONCLUSION: Exposure to palivizumab neither increased the risk of atopic disease nor protected against asthma.

Influence of baseline low-density lipoprotein cholesterol values on statin therapy persistence.

PURPOSE: Persistence to statins is low, in part due to lack of perception of cardiovascular (CV) risk. High values of low-density lipoprotein cholesterol (LDL-C) might increase the motivation for patients to be persistent. We investigated whether the baseline LDL-C value influences the discontinuation of statin treatment in patients with and without previous CV events. METHODS: A cohort study was performed using information from the Swedish national registers concerning dispensed drugs, hospital contacts, cause of death, and socioeconomic status, and linked with data from clinical laboratories. Incident statin users 20 years of age or older and starting treatment between 2006 and 2007 were identified and followed for 1 year. Baseline LDL-C level was defined as the last available laboratory test result during 6 months before the index statin dispensing. Cox regression was used to study discontinuation and estimate the effect on persistence of the baseline LDL-C value adjusting for sex, age, income, comorbidity, previous CV events, type of prescriber, and country of birth. Subgroup analyses stratifying by previous CV events and by diagnosis of diabetes among subjects without previous CV events were performed. RESULTS: A total of 29,389 patients were identified; 35.4% had a previous CV event. A high baseline LDL-C value was associated with a lower discontinuation rate (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.72-0.91) in patients without previous CV events. When stratifying further by diabetes diagnosis, the association was confirmed only in patients without diabetes. No association between LDL-C and persistence was found in patients with previous CV events. CONCLUSIONS: High levels of LDL-C were positively associated with statin persistence in newly treated diabetes patients without previous CV events.

Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins.

OBJECTIVE: This work aims to study the effects of hormone therapy (HT) on the risk of cardiovascular outcomes and all-cause mortality in women treated with statins. METHODS: We included women aged 40 to 74 years and living in Sweden who filled a first statin prescription between 2006 and 2007. Women were categorized as HT users or as nonusers. Information on dispensed drugs, comorbidity, cardiovascular outcomes, and all-cause mortality was obtained from national health registers. RESULTS: A total of 40,958 statin users--2,862 (7%) HT users and 38,096 nonusers--were followed for a mean of 4.0 years. In total, 70% of the women used statins as primary prevention. Among HT users, there were five cardiovascular deaths per 10,000 person-years. The corresponding rate among nonusers was 18, which yielded a hazard ratio of 0.38 (95% CI, 0.12-1.19). The all-cause mortality rates were 33 and 87, respectively, and the hazard ratio was 0.53 (95% CI, 0.34-0.81). There were no associations with cardiovascular events. A similar pattern was found for both primary and secondary prevention. CONCLUSIONS: HT is associated with a reduced risk of all-cause mortality in women treated with statins. Although confounding factors, such as lifestyle and disease severity, might have influenced the results, HT does not seem to be detrimental to statin-treated women.

Family history of cardiovascular disease and influence on statin therapy persistence.

PURPOSE: Persistence to statins is low, presumably due to lack of perception of risk. Having a close relative suffering from cardiovascular disease (CVD) might increase persistence to statins. We investigated whether family history of CVD influences the discontinuation of statin treatment. METHODS: A population-based cohort study was performed. Swedish registers on dispensed drugs, hospitalization and cause of death were linked to the Multi-generation Register. Incident statin users 20-72 years of age were identified between 2006 and 2007 and followed until 30 June 2009. Family history of CVD was defined as the presence of relatives with a previous cardiovascular event. Cox regression was used to study discontinuation and estimate the effect of the family history of CVD, adjusting for gender, age, education, income, healthcare provider, prevention's type, birth's country and residence's county. Stratified analysis by type and severity of cardiovascular event was performed. RESULTS: A total of 86,002 patients were enrolled; 61.5 % had a family history of CVD. Discontinuation of statin therapy was not associated with family history of CVD (HR: 0.98; 95 % CI:0.96-1.01), except for patients with a family history of death from myocardial infarction (MI) (HR: 0.95 95 % CI:0.92-0.98). Young age, foreign background, low income, and statin for primary prevention and for secondary prevention when prescribed by a general practitioner were associated with higher risk of statin discontinuation. CONCLUSIONS: Having relatives suffering from CVD did not consistently influence the persistence to statin treatment. A family history of death from MI had a slight significant positive effect on statin persistence, though not clinically relevant.