A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up

Background: Because asthma is not a curable condition, the development of strategies for prevention of the disease has a high priority. Atopic dermatitis is a common precursor to the development of asthma, and 2 studies have suggested that the use of an H-1 receptor antagonist might reduce the development of asthma while the treatment is being administered, at least in subgroups with evidence of high IgE levels. However, no trial to date has conducted follow-up after the initial treatment has been stopped to establish whether the intervention has merely suppressed symptoms or truly prevented disease. Objective: We sought to establish whether the use of cetirizine compared with placebo for 18 months in infants with atopic dermatitis suppressed or truly delayed the onset of asthma, even after cessation of therapy. Methods: The Early Treatment of the Atopic Child study was a double-blinded, parallel-group, randomized trial of 0.25 mg/kg body weight cetirizine administered twice daily compared with placebo given to infants between I and 2 years of age with atopic dermatitis. After 18 months of treatment, follow-up continued for a further 18 months. This article reports the outcome over the full 3 years of follow-up and relates the outcomes to the allergic status on the basis of IgE antibody measurements at recruitment. Results: Although there was no difference in cumulative prevalence of asthma between active and placebo treatment in the intention-to-treat population (P = .7), those infants with evidence of sensitivity to house dust mite, grass pollen, or both who were treated with cetirizine were significantly less likely to have asthma compared with those treated with placebo over the 18 months of treatment (P = .005 and .002, respectively), and this effect was sustained for the grass pollen-sensitized infants over the full 36 months (P = .008). In the house dust mite-sensitized group there was a gradual narrowing of the difference between active and placebo treatment in terms of cumulative prevalence of asthma at the end of 36 months but no evidence of a rebound immediately after the treatment stopped (P = .04). In the placebo population there was a significantly higher risk of development of asthma in those sensitized at baseline to egg (relative risk, 1.4 [95% CI, 1.1-1.7]), house dust mite (relative risk, 1.6 [95% CI, 1.3-1.9%]), grass pollen (relative risk, 1.7 [95% CI, 1.4-2.1]), or cat (relative risk, 1.5 [95% CI, 1.2-1.9]). Early and persistent sensitization conferred a higher risk than transient or later sensitization. Conclusions: Cetirizine compared with placebo truly delays or, in some cases, prevents the development of asthma in a subgroup of infants with atopic dermatitis sensitized to grass pollen and, to a lesser extent, house dust mite. Further studies are required focusing specifically on sensitized groups to substantiate this finding. The study also highlights risk factors for asthma in infants with atopic dermatitis and indicates that early and persistent aeroallergen sensitization confers a higher risk than later development of sensitivity.