Reduced Atopic March Risk in Pediatric Atopic Dermatitis Patients Prescribed Dupilumab vs Conventional Immunomodulatory Therapy: A Population-Based Cohort Study

This study sought to investigate dupilumab’s effect on the atopic march vs other immunomodulatory (conventional) therapies in pediatric patients with atopic dermatitis (AD).Pediatric patients aged 18 years or younger carrying an AD diagnosis by International Statistical Classification of Diseases, Tenth Revision code twice at least 30 days apart were identified using the TriNetX US Collaborative Network database between 2011 and 2024. Patients prescribed other type 2 immunity-targeting biologics, those with a pre-index diagnosis of asthma or allergic rhinitis (AR), and patients prescribed dupilumab or the other conventional therapies before their first AD diagnosis were excluded.This study used a retrospective cohort design to compare a dupilumab cohort comprising patients prescribed dupilumab with a conventional therapy cohort comprising patients given systemic corticosteroids or other immunomodulators (methotrexate, azathioprine, and cyclosporine). The index date was the first prescription date of either dupilumab or one of the conventional therapies. Cohorts were 1:1 propensity score matched with respect to current age, age at index prescription, sex, race, comorbidities, laboratory measurements, and prior medications. Current and index ages were matched to address period effects. A total of 4384 patients (2192 in each group) met the above inclusion and exclusion criteria and propensity score matching. The primary outcome was atopic march progression defined by incident diagnosis of asthma or AR by a clinician. Secondary outcomes included analyses of asthma and AR symptoms (coughing, wheezing, sneezing, congestion) and prescribed treatments (inhaled corticosteroids, short-acting beta-agonist, nasal spray). Participants were tracked for up to 3 years or until desired outcomes were observed, death, or their last database entry. Statistical analysis was performed using R statistical software and included Kaplan-Meier estimator, log-rank test, and the Cox regression model.In the dupilumab cohort, the mean current age was 8.6 years and mean age at index prescription was 6.9 years. In the conventional therapy cohort, the mean current age was 9.2 years and mean age at index prescription was 7.6 years. Other demographic data were similar between the cohorts: ∼49% female, ∼44% white, ∼23% Black or African American, and ∼7% Asian. Over 3 years, the dupilumab cohort had a significantly lower cumulative incidence of atopic march progression (20.09%) compared with the conventional therapy cohort (27.22%) (P < .001). The dupilumab cohort demonstrated a significantly reduced 3-year cumulative incidence for asthma (9.43% vs 14.64%; P = .001) and AR (13.57% vs 20.52%; P = .003) compared with the conventional therapy cohort. The dupilumab cohort had a significantly lower hazard ratio (HR) of atopic march progression (HR 0.679, 95% CI 0.554–0.831), asthma diagnosis (HR 0.600, 95% CI 0.446–0.808), and AR diagnosis (HR 0.692, 95% CI 0.542–0.882) as well as decreased risks for asthma-associated symptoms (HR 0.403, 95% CI 0.238-0.681), prescription for inhaled controller medication (HR 0.738, 95% CI 0.552–0.988), and inhaled rescue therapies (HR 0.581, 95% CI 0.445–0.759). Additionally, patients in the dupilumab cohort also demonstrated lower HRs for AR-associated symptoms (HR 0.459, 95% CI 0.314–0.671), intranasal corticosteroid prescriptions (HR 0.417, 95% CI 0.265–0.657), and injectable corticosteroid use (HR 0.396, 95% CI 0.293–0.535) compared with the conventional therapy cohort. Age-specific subgroup analyses demonstrated significantly lower risks in the dupilumab cohort for atopic march progression and AR across age groups (preschoolers, school-aged children, and adolescents) but lower risk for asthma in preschoolers only.Pediatric patients with AD prescribed dupilumab had significantly lower risk of developing atopic diseases, primarily asthma and AR, compared with those receiving other systemic therapies. These results suggest a disease-modifying effect of dupilumab in mitigating the atopic march progression.The results of this retrospective review support other research demonstrating a reduction in the atopic march progression in pediatric patients treated with dupilumab. A greater effect was seen in younger-aged patients, suggesting a potential window period of prevention. The strengths of the study include a large database and analysis of multiple potential confounding variables supported by sensitivity analyses, whereas its limitations include its observational design, challenges in diagnosing atopic comorbidities at an early age, lack of objective data to support atopic diagnoses, and lack of information regarding medication dosage and duration. The authors acknowledge the possibility that dupilumab merely alleviates symptoms of asthma and AR, masking or delaying their diagnosis rather than preventing their development. Further research needs to be conducted involving prospective studies with longer follow-up and defining the mechanism of prevention of the atopic march.