Dupilumab May Slow Atopic March in Atopic Dermatitis: Meta-Analysis

Dupilumab lowered the rate of new or worsening allergic conditions by 34% compared with placebo in adolescents and adults with moderate to severe atopic dermatitis, according to a meta-analysis of 12 randomized trials published in the Journal of Allergy and Clinical Immunology.¹

The atopic march is the progressive acquisition of allergic conditions. It classically begins with atopic dermatitis and moves on to food allergy, allergic rhinitis, and asthma, and no intervention had previously been shown to change its course.¹,² Gregory P. Geba, MD, DrPH, and colleagues at Regeneron Pharmaceuticals examined whether interleukin-4 receptor blockade with dupilumab could slow this progression in a highly atopic, mostly adult population.¹

How Was the Dupilumab Atopic March Meta-Analysis Designed?

The investigators pooled 12 randomized, double-blind, placebo-controlled dupilumab trials in moderate to severe atopic dermatitis completed by June 2019, with treatment lasting 4 to 52 weeks. The data set included 3525 patients (2296 receiving dupilumab and 1229 receiving placebo), for a total of 1359 patient-years of exposure.¹

Patients had a median age of 35 years, but their median age at atopic dermatitis onset was 2 years. At baseline, patients had an average of 3.4 allergic conditions in addition to atopic dermatitis, and allergic burden was comparable between arms.¹

A board-certified allergist blinded to treatment assignment grouped allergy-related adverse events into 17 categories, excluding atopic dermatitis terms. Each new or worsened event in a category counted as 1 step of the atopic march. The investigators also tracked changes in IgE category from baseline and compared groups using incidence rate ratios (IRRs).¹

Did Dupilumab Reduce New and Worsening Allergies?

During treatment, dupilumab reduced the risk of new or worsening allergies by 34% versus placebo (IRR, 0.66; 95% CI, 0.52-0.84) and the risk of new allergies alone by 37% (IRR, 0.63; 95% CI, 0.48-0.83). Asthma, pruritus, and urticaria contributed most to the overall effect.¹

When 1-step increases in IgE category were added, the reduction in combined new or worsening events reached 54% (IRR, 0.46; 95% CI, 0.37-0.56). A more conservative 2-step IgE definition still showed a 39% reduction (IRR, 0.61; 95% CI, 0.49-0.76). The results held in a sensitivity analysis excluding all skin events.¹

Over the full study period, including off-treatment follow-up, the effect was smaller but persisted (new or worsening events: IRR, 0.72; 95% CI, 0.58-0.90). The authors reported no rebound in allergic events after dupilumab was stopped.¹

Which Patients with Atopic Dermatitis Benefited Most?

Based on the shifts in point estimates, the benefit were shown to be greater in patients younger than 18 years, those whose atopic dermatitis began before 2 years of age, those with more severe disease at baseline, and those with asthma at baseline. Patients with 2 or more other allergic conditions and those with a baseline IgE of 375 to 2000 IU/mL also appeared to benefit more.¹

The investigators acknowledged mean follow-up was short, at about 0.39 years. They called for larger, longer trials to confirm durability and to evaluate younger patients and those with milder atopic dermatitis. All authors were employees of Regeneron, which funded the analysis.¹

Editor's Note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. Geba GP, Li D, Xu M, et al. Attenuating the atopic march: meta-analysis of the dupilumab atopic dermatitis database for incident allergic events. J Allergy Clin Immunol. 2023;151(3):756-766. doi:10.1016/j.jaci.2022.08.026.

2. Hill DA, Spergel JM. The atopic march: critical evidence and clinical relevance. Ann Allergy Asthma Immunol. 2018;120(2):131-137. doi:10.1016/j.anai.2017.10.037.