Efficacy of Dupilumab in Children with Atopic Dermatitis | Insights from AAD 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic skin lesions.¹ It is the most common chronic inflammatory skin disease in children.¹ Dupilumab (Regeneron Pharmaceuticals and Sanofi Genzyme) is a monoclonal antibody and interleukin-4 (IL-4) receptor alpha inhibitor that downregulates the type 2 inflammatory pathway through the inhibition of IL-4 and IL-13 signalling.² It has been approved for the treatment of severe AD in children older than 6 months.^3,4

An on-going open-label extension phase III trial (ClinicalTrials.gov identifier: NCT02612454) is investigating the safety of dupilumab in patients aged 6 months to 17 years with moderate-to-severe atopic dermatitis (AD) who completed the parent study Liberty AD PRESCHOOL (ClinicalTrials.gov identifier: NCT03346434).^5,6 The interim results of this trial have shown that long-term treatment is well tolerated with an acceptable safety profile. Dr Amy Paller provided an overview of this study.

The parent study (Liberty AD PRESCHOOL) investigated weight-based dupilumab in children aged 6 months to 5 years, demonstrating an acceptable safety profile.⁶ At week 16, this trial reported that 27.7% of patients receiving dupilumab achieved an Investigator’s Global Assessment score of 0–1 (p<0.001) compared with 3.9% of patients in the placebo arm and 53.0% achieved ≥75% improvement in Eczema Area and Severity Index compared with 10.7% (p<0.001), respectively. Drug-related treatment-emergent adverse events (TEAE) of any grade were reported in 10.8% patients receiving dupilumab (n=83) compared with 6.4% of patients in the control arm of placebo plus topical corticosteroid (n=78).^6,7 Dr Paller remarked, “Dupilumab not only came out on top by far, but also proved to be as safe in that study … as it had been in the previous trials in children, adolescents and adults.” 

The open-label extension investigating the safety of dupilumab in children aged 6 months to 17 years up to 52 weeks reported 8.3% of patients with drug-related treatment-emergent adverse events of any grade (N=180).⁶ The most common adverse events in the open-label extension included nasopharyngitis (12.8%), upper respiratory tract infection (11.7%) and cough (8.3%).⁶

Speaking about questions that remain unanswered in the use of dupilumab in children, Dr Paller said, “This is, first of all, an age group where live immunizations are given. […] This medication targets the type 2 immune system and we don’t know that that system has anything to do with response or the safety in managing vaccinations that are live. There’s been no study of live vaccines.” Currently, both the US Food and Drug Administration product information and the European Medicines Agency summary of product characteristics recommend against the use of live vaccines in patients on dupilumab therapy.^3,4

Dr Paller went on to discuss how these findings may be used to inform future treatment decisions, commenting, “The other question that that raises is whether there is any effect on the immune system as it’s developing early enough that we can change the course of the atopic dermatitis and even possibly cure it in these moderate to severely affected young children.” Another question that these findings raise is “whether we can prevent, with the early use of this medication, the development of other forms of atopy, asthma, eosinophilic esophagitis or even later allergic rhinitis.”

The full video interview with Dr Paller is available on touchIMMUNOLOGY here.

The abstract discussed in this interview is the following:

Treatment-Emergent Adverse Events in Patients Aged 6 Months to 5 Years With Moderate-to-Severe Atopic Dermatitis Treated With Dupilumab in an Open-Label Extension Clinical Trial.

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References:

1. Huang E, Ong PY. Severe atopic dermatitis in children. Curr Allergy Asthma Rep. 2018;18:35.
2. Le Floc’h A, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020;75:1188–204.
3. European Medicines Agency. Dupixent: Summary of product characteristics. 2023. Available at: www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf (Date last accessed: 16 August 2023).
4. US Food and Drug Adminsitration. DUPIXENT® (dupilumab) prescribing information.2022. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2022/761055s042lbl.pdf (Date last accessed; 16 August 2023).
5. ClinicalTrials.gov. Study to Assess the Long-term Safety of Dupilumab Administered in Participants ≥6 Months to <18 Years of Age With Atopic Dermatitis (AD). ClinicalTrials.gov Identifier: NCT02612454. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT02612454 (Date last accessed: 16 August 2023).
6. Paller AS, Siegfried EC, Sidbury R, et al. 437 Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial. Br J Dermatol. 2023;188(Suppl. 3):ljad162.057. doi:10.1093/bjd/ljad162.057