Association between hospital-diagnosed atopic dermatitis and psychiatric disorders and medication use in childhood.

BACKGROUND: While adult atopic dermatitis (AD) is associated with anxiety and depression, and paediatric AD is linked to attention deficit hyperactivity disorder (ADHD), the relationship between AD in childhood and other psychiatric disorders is largely unknown. OBJECTIVES: To determine the relationship between AD and diagnosis and treatment of psychiatric disorders in children. METHODS: All Danish children born between 1 January 1995 and 31 December 2012 with a hospital diagnosis of AD (n = 14 283) were matched 1 : 10 with children without a hospital diagnosis of AD. Endpoints were psychotropic medication use, hospital diagnoses of depression, anxiety, ADHD, or self-harming behaviour, accidental/suicidal death, and consultation with a psychiatrist or psychologist. RESULTS: Significant associations were observed between hospital-diagnosed AD and antidepressant [adjusted hazard ratio (aHR) 1·19, 95% confidence interval (CI) 1·04-1·36], anxiolytic (aHR 1·72, 95% CI 1·57-1·90), and centrally acting sympathomimetic (aHR 1·29, 95% CI 1·18-1·42) medication use. Consultation with a psychiatrist (aHR 1·33, 95% CI 1·16-1·52) or psychologist (aHR 1·25, 95% CI 1·11-1·41) was also associated with AD. No association with a hospital diagnosis of depression (aHR 0·58, 95% CI 0·21-1·56), anxiety (aHR 1·47, 95% CI 0·98-2·22) or self-harming behaviour (aHR 0·88, 95% CI 0·27-2·88) was observed, but a diagnosis of ADHD (aHR 1·91, 95% CI 1·56-2·32) was significantly associated with AD. The absolute risks were generally low. CONCLUSIONS: The increased risk of treatment, but not of a hospital diagnosis of psychiatric disorders in children with hospital-diagnosed AD, suggests that psychiatric issues in children with AD could be of a transient, reversible or mild-moderate nature.

Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study.

BACKGROUND: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking. OBJECTIVES: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. METHODS: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg-1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg-1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score. RESULTS: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg-1 , 61-77 mg L-1 ; 4 mg kg-1 , 143-181 mg L-1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg-1 , 47%; 4 mg kg-1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively. CONCLUSIONS: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD.

Cardiovascular comorbidities are increased in U.S. patients with haemophilia A: a retrospective database analysis.

There is conflicting evidence in the literature on whether individuals with haemophilia in the USA have greater, reduced, or similar risks for cardiovascular disease as the general population. This study evaluated the prevalence of cardiovascular comorbidities among USA males with haemophilia A, relative to an unaffected general male population with similar characteristics. Males with haemophilia A and continuous insurance coverage were identified by ICD-9-CM code 286.0 (1 January 2007-31 December 2009) using the MarketScan Commercial and Medicare Research Databases. Individuals with haemophilia A were exact matched 1:3 with males without a diagnosis of haemophilia A. The prevalence of cardiovascular comorbidities identified by ICD-9-CM code was determined for matched cohorts. Of the study population, 2506 were grouped in the haemophilia A cohort and 7518 in the general cohort. Proportions of individuals with haemorrhagic stroke (2.0% vs. 0.5%, P < 0.001), ischemic stroke (4.7% vs. 2.7%, P < 0.001), coronary artery disease (10.7% vs. 5.8%, P < 0.001), myocardial infarction (0.8% vs. 0.3%, P = 0.003), hypertension (22.6% vs. 15.5%, P < 0.001), hyperlipidaemia (15.9% vs. 11.9%, P < 0.001), arterial thrombosis (12.1% vs. 5.9%, P < 0.001), and venous thrombosis (4.4% vs. 1.1%, P < 0.001) were significantly greater for the haemophilia A cohort. Results were consistent across most age groups, and comorbidities appeared at an earlier age in those with haemophilia A than in the general population. Among the USA haemophilia A population cardiovascular comorbidities are more prevalent and they appear earlier in life in comparison to the general male population, suggesting the need for earlier, enhanced screening for age-related comorbidities in the haemophilia community.