Research in context
Evidence before this study
Findings of previous phase 1 and 2a studies showed preliminary efficacy and a favourable safety profile of dupilumab in patients with atopic dermatitis, asthma, and chronic sinusitis with nasal polyposis. To obtain information about the unmet need for systemic treatment of atopic dermatitis, we searched PubMed and Embase on Feb 27, 2015, for randomised, controlled, blinded clinical trials of systemic immunosuppressant treatments and oral glucocorticoids for treatment of moderate-to-severe atopic dermatitis published in English language. Additionally, we searched the reference lists of recent treatment guidelines and a recent systematic review of systemic treatments in patients with atopic dermatitis. We used the following search terms: “atopic dermatitis”, “eczema”, “cyclosporine”, “ciclosporin”, “methotrexate”, “azathioprine”, “mycophenolate”, “interferon-γ”, “intravenous immunoglobulin”, “prednisone”, “prednisolone”, “dexamethasone”, “beclomethasone”, and “methylprednisolone”. Overall, we identified 22 randomised, controlled, blinded studies. Systemic immunosuppressant treatments were effective in moderate-to-severe atopic dermatitis, but were associated with toxic effects, especially with long-term treatment, and systemic corticosteroids were associated with rebound effects. As noted in current guidelines, with the exception of ciclosporin, which is approved in some countries, most systemic immunosuppressant treatments are not approved for moderate-to-severe atopic dermatitis, except in cases of refractory disease, indicating a substantial unmet need.
Added value of this study
Our results showed the clinical efficacy of dupilumab at five different dose regimens in patients with moderate-to-severe atopic dermatitis, with the most consistent benefits recorded with dose regimens of 300 mg once a week and 300 mg every 2 weeks. Consistent with findings of previous phase 1 and 2a studies, dupilumab had a favourable safety profile with no dose-limiting toxic effects. Our findings confirmed the efficacy reported in the previous early-phase studies. Our study used the longest duration of treatment reported up to now for this drug; was the first study of dupilumab in atopic dermatitis assessing several dose regimens given less frequently than weekly, including less-frequent doses lower than 300 mg, which provided data to optimise treatment regimens; and was the largest study of dupilumab so far and, therefore, provides important safety information.
Implications of all the available evidence
There is an unmet need for a safe and effective systemic treatment for patients with moderate-to-severe atopic dermatitis (especially those with an inadequate response or who cannot tolerate current treatment) because approved treatments are often ineffective or associated with adverse effects and, therefore, are unsuitable for the long-term management of atopic dermatitis. Our findings showed a positive benefit–risk ratio for dupilumab, which specifically targets the Th2-mediated inflammation driving atopic dermatitis. Phase 3 confirmatory studies are underway investigating dupilumab as monotherapy, and in combination with topical corticosteroids; these studies are larger and of longer duration than the present study, and will further evaluate the efficacy and safety of dupilumab at doses of 300 mg once a week and every 2 weeks, the two dose regimens selected from the present study, in patients with moderate-to-severe atopic dermatitis.