Strategies for measuring long-term control in atopic dermatitis trials: a systematic review

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardised methods for capturing long-term control of AD. Objective: To identify how long-term control has been captured in published randomised controlled trials (RCTs). Resultswill initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. Methods: Systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of ≥3 months, at least one outcome measure recorded at ≥3 time-points, full paper available, and published in English. Results: 101/ 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%); and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly for trials including flare data (21/52). Medication-use was recorded based on quantity, potency and frequency of application. Limitations: Included RCT data only Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes

The burden of childhood atopic dermatitis in the primary care setting: a report from the Meta-LARC Consortium

Background: Little is known about the burden of AD encountered in U.S. primary care practices and the frequency and type of skin care practices routinely used in children. Objectives: To estimate the prevalence of AD and allergic comorbidities in children 0-5 years attending primary care practices in the U.S. and to describe routine skin care practices used in this population. Design: A cross-sectional survey study of a convenience sample of children under the age of 5 attending primary care practices for any reason. Setting: Ten primary care practices in five U.S. states.Results: Amongst 652 children attending primary care practices, the estimated prevalence of ever having AD was 24 % (95% CI= 21-28) ranging from 15% among those under the age of one to 38% among those aged 4- 5 years. The prevalence of comorbid asthma was higher among AD participants compared to those with no AD, 12% and 4%, respectively (p less than 0.001). Moisturizers with high water:oil ratios were most commonly used (i.e., lotions) in the non-AD population, whereas moisturizers with low water:oil content (i.e. ointments) most common when AD was present. Conclusions: Our study found a large burden of AD in the primary care practice setting in the U.S. The majority of households reported skin care practices in children without AD that may be detrimental to the skin barrier such as frequent bathing and the routine use of moisturizers with high water: oil ratios. Clinical trials are needed to identify which skin care practices are optimal for reducing the significant risk of AD in the community

Priority research questions in atopic dermatitis : an International Eczema Council eDelphi consensus

Recent advances in understanding the complex pathogenesis of atopic dermatitis (AD, also known as eczema or atopic eczema), coupled with the development of new treatments, have led to increased interest from multiple stakeholders. There is a need to prioritize areas for research to inform a coordinated approach to advancing science and patient care

Phosphodiesterase Inhibition by Ro 20-1724 Reduces Hyper-IgE Synthesis by Atopic Dermatitis Cells In Vitro

Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10-4 M and 10-5 M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p <0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified “panning” method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ho 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phophodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously indescribed link between cAMP PDE levels and in vitro IgE synthesis