Dupilumab Now Covered for Atopic Dermatitis in Children Older Than 6 Years

Indications for Dupilumab and Evaluation of Therapy Success

Dupilumab (a recombinant human monoclonal antibody of the IgG4 class that inhibits the signaling pathways of interleukins IL-4 and IL-13) is covered for adult patients with severe atopic dermatitis (AD) who have failed (shown insufficient efficacy) at least one conventional systemic immunosuppressive therapy (excluding corticosteroids). It is also indicated for patients who cannot be treated with systemic therapy due to intolerance or contraindications.

Furthermore, it is covered for adolescent patients from the age of 12 and, since October 2021, also for children aged 6 to 11 years with severe AD who have not achieved disease control with maximal local therapy, phototherapy, or balneotherapy.

It is administered subcutaneously in centers specialized in biological treatment of AD and can be combined with topical corticosteroids and calcineurin inhibitors (cyclosporine). The success of the therapy is evaluated after 16 and 24 weeks from its start and thereafter at least every 24 weeks. Therapy will be terminated in the following cases:

• failure to achieve at least EASI-50 (a 50% improvement in the Eczema Area and Severity Index score) by week 16
• failure to achieve at least EASI-75 by week 24
• occurrence of serious adverse reactions
• insufficient adherence to therapy
• decline in efficacy below EASI-50 at two consecutive evaluations

For already treated adolescent patients, dupilumab therapy continues after reaching 18 years of age without the condition of prior conventional systemic therapy.

Study Results in Children Aged 6-11 Years

A total of 367 participants (average age 8.5 years; 50.1% girls) were included in a multicenter, randomized, double-blind, placebo-controlled study. Severe atopic dermatitis was defined by an IGA (Investigator Global Assessment) score of 4, EASI ≥ 21 (baseline mean value 37.9), and a minimum body surface area (BSA) involvement of ≥ 15% (baseline mean value 57.6%). They were stratified by body weight into two groups: < 30 kg and ≥ 30 kg.

Dupilumab dosing was as follows:

• initial dose of 200 mg followed by 100 mg every 2 weeks up to week 14 (for patients with body weight < 30 kg)
• initial dose of 400 mg followed by 200 mg every 2 weeks up to week 14 (for patients with body weight ≥ 30 kg)
• initial dose of 600 mg followed by 300 mg every 4 weeks up to week 12 regardless of body weight

The proportion of patients achieving an IGA score of 0 or 1 (“clear” or “almost clear” skin) with an improvement of at least 2 points was higher in the dupilumab group (32.8% with application every 4 weeks and 39.0% with application every 2 weeks) compared to the placebo group (11.4% and 9.7%). Additionally, the proportion of patients with at least a 75% improvement in the EASI score by week 16 compared to baseline was 69.7% and 74.6% in the dupilumab group versus 26.8% and 25.8% in the placebo group. A higher proportion of patients randomized to dupilumab treatment achieved maximum pruritus score improvement on the NRS scale compared to placebo by week 4. Significant improvements in the impact of AD on sleep and health-related quality of life measured by overall POEM, SCORAD, and CDLQI scores were also observed by week 16.

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Sources:

1. Paller A. S., Siegfried E. C., Thaçi D. et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol 2020; 83 (5): 1282-1293, doi: 10.1016/j.jaad.2020.06.054.
2. SPC Dupixent. Available at: www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_cs.pdf
3. Dupixent. Sanofi and Regeneron Pharmaceuticals, 2021 Oct. Available at: www.dupixent.com/atopicdermatitis