The effectiveness and cost-effectiveness of treatment with systemic cyclosporine or dupilumab in children with moderate-to-severe atopic dermatitis is different for patients with low NMF (corresponding with filaggrine-gene mutation) versus children…
ID
Bron
Verkorte titel
Aandoening
Atopic dermatitis
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- Relative reduction in EASI (Eczema Area and Severity Index, EASI) at t = 6 months
- Proportion of patients that achieved EASI75 (relative reduction of 75% from baseline EASI) without the use of rescue medication, at t = 6 months
Achtergrond van het onderzoek
If topical therapy fails, the next step for treatment of moderate-to-severe atopic dermatitis (AD) in children is systemic therapy. Systemic cyclosporine A (CsA), is the first choice according to the national guidelines. Unfortunately, about 22.5-36% patients are refractory to CsA. In addition, treatment of AD in children with systemic CsA is expensive (€7.000/year). Prognostic tools for effective use of CsA are lacking, resulting in over- and under treatment. AD is a heterogeneous disease with various biological origins and clinical appearances. Dupilumab (Dupixent) is a newly registered biological for the treatment of pediatric atopic dermatitis with promising results, but also lacking in prognostic tools. It is likely that different therapies or treatment intensities are not equally effective for all AD endotypes. The strongest genetic risk factor for AD is a null mutation in the filaggrin gene (FLG). Stratification of patients based on the FLG null endotype could enable more targeted treatment. In current clinical practice FLG-null mutations are not determined for AD, since genotyping is costly, slow and requires a high level of expertise. The Natural Moisturizing Factor (NMF) biomarker, measured by Raman spectroscopy, is an accurate surrogate marker for the presence of FLG-null mutations. The goal of this study is to investigate whether stratification of children with atopic dermatitis on the NMF biomarkers results in an improvement of effectiveness and efficiency in the use of systemic treatment (ciclosporin and dupilumab) in moderate-to-severe atopic dermatitis.
Doel van het onderzoek
The effectiveness and cost-effectiveness of treatment with systemic cyclosporine or dupilumab in children with moderate-to-severe atopic dermatitis is different for patients with low NMF (corresponding with filaggrine-gene mutation) versus children with normal NMF (corresponding with filaggrine wildtype).
Onderzoeksopzet
t = 0, 1, 2, 3 and 6 months
Onderzoeksproduct en/of interventie
Systemic cyclosporine A or dupilumab for 6 months
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Children and adolescents, aged between 2 and 18, with moderate to severe atopic dermatitis (diagnosed according to the UK working party criteria)
- Patients and parents/guardians able to participate in the study and willing to give written informed consent
- EASI (Eczema Area Severity Index) ≥ 6 at screening and baseline (corresponding with moderate-to-severe disease)
- IGA (Investigators Global Assessment) ≥ 3 at screening and baseline (corresponding with moderate-to-severe disease)
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- children under the age of 2 years (due to the prescribe conditions of CsA) and patients older than 18 years
- contraindication for CsA or dupilumab
- use of topical corticosteroids (TCS) or topical calcineurine inhibitors (TCI) 2 weeks before randomization (during the washout period)
- use of systemic anti-inflammatory medication 4 weeks before randomization
- patient (or one of the parents/guardians) not willing to be randomized
- children with a history of any known primary immunodeficiency disorder
- children with a history of cancer
- EASI < 6 at screening or at baseline
- IGA <3 at screening or at baseline
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7967 |
| Ander register | METC Erasmus MC Rotterdam : MEC-2019-0568 |