Dupilumab Shows Durable 2-Year Efficacy in Pediatric AD

Dupilumab, a fully human monoclonal antibody targeting interleukin (IL)-4 and IL-13 signaling, has transformed the management of moderate to severe atopic dermatitis (AD). While clinical trials have demonstrated its efficacy and safety in pediatric populations, real-world data, particularly over extended treatment periods, remain limited.¹ Traini et al recently presented a 2-year retrospective, single-center observational study from the Fondazione Policlinico Universitario A. Gemelli-IRCCS in Rome, offering valuable long-term insights into dupilumab therapy in children and adolescents, including those with syndromic comorbidities.²

Study Design and Population

The study included 42 pediatric patients (ages 6-18 years) with moderate to severe AD unresponsive to topical therapy. Inclusion followed Italian Medicines Agency (AIFA) criteria: EASI ≥ 24, or involvement of sensitive areas combined with pruritus NRS ≥ 7 and cDLQI ≥ 10. The cohort had a mean age of 15.3 years (SD ± 3.7), with 19% under 11 years. AD onset before age 1 occurred in 62% of participants, reflecting early and persistent disease courses. Over half (54.8%) had atopic comorbidities, most commonly asthma and allergic rhinitis, and 6 had rare genetic syndromes, including Down syndrome, Costello syndrome, and chromosomal deletions.

Dupilumab dosing followed EMA-approved regimens, adjusted for weight and age. During the summer months (June to August), all patients underwent a physician-directed dosing interval extension (e.g., from every 2 weeks to 3-5 weeks), leveraging the seasonal amelioration of AD symptoms. Clinical assessments were performed at baseline, week 4, week 16, and 6, 12, and 24 months, with EASI, pruritus (P-NRS), and sleep (S-NRS) scores tracked longitudinally.

Key Outcomes

Efficacy:
By week 4, mean EASI decreased from 21.2 to 10.3 (p < 0.001); by week 16, it had decreased to 6.1. Two patients (4.7%) discontinued treatment for lack of response. At 16 weeks, 95% achieved EASI-50, 65% achieved EASI-75, and 7.3% achieved EASI-90. Sustained improvement was observed through 24 months: mean EASI 1.6 (−91.5% from baseline, p < 0.0001). Pruritus and sleep parameters paralleled these gains—mean P-NRS fell from 8.75 to 1.6, and S-NRS from 5.5 to 0.8 at 24 months.

Seasonal dosing modulation:
All patients maintained disease control (EASI < 3) during the summer dosing extension. However, at autumn reassessment, 50% (21/42) experienced mild flares (EASI ≥ 3), necessitating return to standard dosing. Baseline characteristics—including age, sex, and initial disease severity—did not predict which patients sustained control on the extended schedule, suggesting that environmental and immunologic factors rather than fixed demographics influence dose sensitivity.

Subgroup findings:
Children with genetic syndromes tolerated dupilumab well and achieved meaningful clinical improvement. No severe adverse events (AEs) were reported. Two nonresponders included a child with coexistent alopecia areata, consistent with previous reports of variable dupilumab efficacy in that condition.

Safety Profile

Dupilumab was well tolerated across the cohort. The only adverse event was mild, self-limited conjunctivitis in 9.5% of patients, managed conservatively without discontinuation. No systemic AEs, injection-site reactions, or BMI changes were observed. This safety profile aligns with pivotal pediatric trial data and other real-world experiences, reinforcing dupilumab’s favorable tolerability in long-term pediatric use.

Clinical and Practical Implications

This study strengthens the evidence base supporting dupilumab as a safe, durable systemic option for pediatric AD, including complex or syndromic cases. Clinically, it suggests several takeaways:

1. Durable efficacy: Sustained disease control and pruritus relief were maintained over 24 months, with progressive improvement in quality-of-life metrics.
2. Safety consistency: The AE profile mirrored that observed in controlled studies, without new long-term safety signals.
3. Seasonal dose flexibility: Real-world feasibility of summer interval extension highlights a potential strategy for tailoring biologic therapy based on environmental triggers, though prospective validation is required.

Limitations and Future Directions

The study’s retrospective, single-center design and modest sample size limit generalizability. Seasonal dose adjustment was observational rather than randomized, and confounding from environmental factors cannot be excluded. Nevertheless, the inclusion of patients with rare genetic comorbidities provides unique insight into a population often excluded from trials.

Future multicenter, prospective studies with larger pediatric cohorts are warranted to confirm these findings, identify predictors of sustained response, and define optimal frameworks for biologic dose modulation. Integration of real-world pharmacokinetic and biomarker data may also clarify whether seasonal adjustment strategies can safely minimize treatment burden while maintaining disease control.

References

1. Koskeridis F, Evangelou E, Ntzani EE, Kostikas K, Tsabouri S. Treatment with dupilumab in patients with atopic dermatitis: Systematic review and meta-analysis. J Cutan Med Surg. 2022;26(6):613-621. doi:10.1177/12034754221130969
2. Traini D, Guerriero C, et al. Long-term dupilumab efficacy and safety in pediatric patients: A real-world experience over 2 years. Dermatol Ther. 2025. doi: 10.1155/dth/4857510.