An ongoing longitudinal study is investigating whether early and continued treatment of atopic dermatitis with the topical immunomodulator pimecrolimus 1 percent cream (Elidel, Novartis) can prevent future development of asthma and other allergies. The multicenter trial was launched more than three years ago and randomized 1,091 children ages 3 months to 18 months old. An analysis of the demographic features of the study population highlights the value of the cohort for investigating a number of questions about AD and allergies.
Portland, Ore. - An interim analysis of the demographic characteristics of infants enrolled in the ongoing longitudinal trial investigating whether early and continued treatment of atopic dermatitis (AD) with a topical immunomodulator alters risk of future development of asthma and other allergies reaffirms that the recruited patient population is well- suited to answer that primary study question.
It highlights that the available cohort offers a rich data source for exploring a broad range of research questions regarding the clinical course of AD and allergy development.
Jon M. Hanifin, M.D., discusses the findings that he and his co-investigators extrapolated from the demographic analysis of the study's participants. The trial randomized 1,091 children ages 3 months to 18 months old with a diagnosis of AD according to American Academy of Dermatology Consensus Conference criteria, and who had at least one immediate family member with atopic disease.
The study began almost three years ago with a three-year, double-blind treatment phase during which enrolled children were randomized to treatment of active atopic dermatitis with pimecrolimus cream 1 percent (Elidel, Novartis) or vehicle.
In both arms, children could be treated with fluticasone propionate 0.05 percent cream (Cutivate, GlaxoSmithKline) as a rescue medication if needed after three days. Then, treatment was continued until the atopic dermatitis cleared and restarted as needed. At the end of three years, all children who had not developed asthma entered the open-label phase where they were treated over another three years for AD flares with pimecrolimus cream.
"Many AD studies are academic center-based and enroll the more severely affected patients who present to a tertiary center. The children enrolled in this large trial have a broader range of disease severity and are more representative of children affected with AD in the general population," says Dr. Hanifin, professor of dermatology, Oregon Health & Science University, Portland, Ore.
"While that may mean the rate of asthma development will be less than reported in populations with more severe AD, the children in this study are at increased risk for asthma because they all have an atopic family history. Therefore, we expect to be able to answer whether early intervention for AD makes a difference in asthma risk."
The children enrolled had a mean age of about 8 months, and the majority were younger than 1 year old (84 percent), male (62 percent) and white (69 percent). To be eligible for enrollment, patients were required to have an Investigator's Global Assessment (IGA) score for atopic dermatitis severity of at least "2" (0 = clear; 2 = mild; 5 = very severe). More than 90 percent of enrolled children had mild or moderate AD, according to the IGA ratings. Mean body surface area affected was about 18 percent, and the mean Eczema Area and Severity Index (EASI) score at baseline was 6.4 (maximum possible score, 72).
Fewer than 10 percent of the children were regularly exposed to cigarette smoke, but 42 percent had pets in the home. Other data collected on factors that may influence asthma development, including breastfeeding history, family history and allergy history, were analyzed.
Almost all children were using some pharmacological or nonpharmacological therapy to control their skin disease, with the most common modalities being emollients (54 percent) and a weak corticosteroid (31 percent).
Serum was tested for total IgE in 85 percent of children at baseline, and an elevated level was found in all.
When the children were stratified based on IGA score, mean total IgE was higher in patients with moderate versus mild AD severity, whether considering data from the total population or after they were subdivided by age (≤1 year, >1 year).
The finding of elevated IgE levels in all of these young children is consistent with the concept that allergen sensitization occurs through the disrupted skin barrier in persons with AD. In 2000, Dr. Hanifin and colleagues postulated that a disrupted skin barrier in children with AD could provide a portal for systemic entry of allergens that could incite the immunologic cascade leading to the development of asthma and other allergies.
Dr. Hanifin points out that in 2006, investigators published findings reporting that loss of function mutations in the gene for filaggrin, a protein critical for formation of the epithelial barrier, predisposed to AD and to development of asthma in those patients.
"That discovery has been a potent stimulus for further studies of barrier dysfunction in AD and asthma. Our trial - well under way and studying a wide range of variables in a large infant population - may provide guidance to future barrier and prevention focused research," he says.
Disclosure: The study is being supported by Novartis Pharmaceuticals. Dr. Hanifin has been a consultant and an investigator in clinical trials for Novartis.