Study of the Atopic March: Development of Atopic Comorbidities

Abstract

Background: Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma or allergic rhinitis. The goal of this study was to determine whether early intervention with pimecrolimus limits the atopic march in infants with AD and to evaluate its efficacy and safety.

Methods: This was a 3-year double-blind study in which patients were randomized to pimecrolimus or vehicle and then open-label pimecrolimus for a planned further 3 years. Rescue topical corticosteroid was permitted if 3 days of study medication led to no improvement; investigators made decisions on rescue medication until week 14 and caregivers thereafter. Efficacy assessments included disease-free days, Eczema Area and Severity Index, and body surface area affected.

Results: Infants ages 3 to 18 months with recent-onset AD (≤3 months) were observed for a mean of 2.8 years (N = 1,091). No significant differences between pimecrolimus- and placebo-treated groups were found in the percentage of patients with AD who developed asthma (10.7%) or other allergic conditions (allergic rhinitis, 22.4%; food allergy, 15.9%; allergic conjunctivitis, 14.1%; one or more atopic comorbidities, 37.0%) by study end. Allergic rhinitis, food allergy, and having one or more atopic comorbidities (but not asthma or allergic conjunctivitis alone) developed significantly more often in infants with greater AD severity at baseline. Pimecrolimus was significantly more effective than vehicle for AD treatment at week 14. Adverse event incidences were similar.

Conclusions: This longitudinal observation of infants with AD provides evidence of the atopic march. Pimecrolimus was safe and effective in infants with mild to moderate AD.

Figure 1

Dose escalation scheme. All patients received emollient only during Treatment Step 1. During Treatment Step 2, patients were randomized 1:1 to twice-daily pimecrolimus 1% or vehicle-only cream. Patients received add-on once-daily TCS in Treatment Step 3a (medium strength) or Treatment Step 3b (potent). With severe disease exacerbations, an oral agent was used in Treatment Step 4. AD, atopic dermatitis; TCS, topical corticosteroid.

Figure 2

Patient disposition. *Safety population included all randomized patients who were dispensed study medication. ^†Intent-to-treat (ITT) population included all randomized patients who were dispensed study medication and had one or more postbaseline efficacy measurements. ‡Study was terminated early based on independent scientific advisory board recommendation of the double-blind phase results (i.e., the proportion of disease-free days in Treatment Step 2 [pimecrolimus or vehicle] or Step 1 [emollient] did not reach statistical significance).

Figure 3

Development of atopic comorbidities (A) in the intent-to-treat (ITT) population and (B) according to baseline Investigator Global Assessment (IGA). *p < 0.05. At the end of the double-blind (DB) phase, patients in the pimecrolimus 1% cream (Pim) group continued treatment and those in the control group changed to Pim. AC, allergic conjunctivitis; AR, allergic rhinitis.