Attenuating the atopic march: a dupilumab atopic dermatitis database meta-analysis
Published: September 6, 2022
Atopic march is typically associated with progressive allergic disease burden starting from infancy through adolescence, which generally begins with atopic dermatitis (AD), followed by food allergy and then allergic diseases of the airways, before the development of other broader or worsened allergic conditions. Allergic immune responses are characterized by the presence of several markers in the blood, including allergen-specific immunoglobulin (Ig)E. The risk of atopic march is higher in children who produce IgE antibodies in response to environmental triggers compared with those who do not. In addition, IgE sensitization, early onset AD, and more severe AD are all known predictors of later atopic diseases, such as asthma. Currently, there are no known disease-modifying interventions for the progressive allergic disease burden associated with atopic march, which are driven by allergic inflammatory signals. Therefore, treatments that can reduce the incidence of new and worsening allergic events and that can interfere with the progression of atopy are of interest. Previously, dupilumab, a monoclonal antibody that is designed to block IL-4R, has demonstrated effectiveness in the treatment of moderate-to-severe AD and other allergic conditions that are largely driven by type 2 inflammation.
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Geba et al report on the results of a meta-analysis assessing whether the rate of acquisition of new or worsening of existing allergic events was reduced with dupilumab versus placebo in patients with AD from a large AD clinical trial database. Allergy-associated events from 12 clinical trials were defined. All enrolled patients had moderate-to-severe AD at baseline not adequately controlled with topical medications. In the 12 clinical trials, dupilumab was used, with most patients receiving 300 mg weekly or every two weeks. The majority of trials studied dupilumab as a monotherapy, while 1 long-term study added dupilumab or a placebo to topical corticosteroids. Allergic-related treatment-emergent adverse events (TEAEs) were assessed to track the effectiveness of treatment on new or existing allergic events. A new/worsened event was considered as one step of atopic march. The treatment effect was assessed by incidence rate ratios reflecting relative differences in rate between for dupilumab versus placebo.
The duration of pooled AD studies was 4 to 52 weeks, corresponding to 1359 patient-years in total (2296 patients in dupilumab group; 1229 patients in placebo group). The median age at AD onset was 2 years; the average age at AD onset was 9 years. At the start of studies, the baseline allergic disease burden was similar between dupilumab and placebo treatment groups. During the treatment period, dupilumab reduced the rate of new or worsening allergies by 34% (95% confidence interval [CI]: 16%, 48%) and new allergies by 37% (95% CI: 17%, 52%) versus placebo. When IgE category shift (1-step increase) was included in the analyses, the rate for combined new or worsening allergies was further reduced by 54%. Treatment benefits did not reverse during the off-treatment follow-up period.
Across the large adolescent and adult AD clinical database, treatment with dupilumab was seen to reduce the acquisition of new or worsened allergy events compared with placebo. This analysis offers important evidence on the possibility that dupilumab may offer effective management of allergic burden in these individuals with AD over time. Larger trials of longer duration across an even broader spectrum of age and disease severity are required to confirm whether dupilumab can significantly and durably exert these effects, affecting the underlying atopic march.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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