Dupilumab versus Placebo in Atopic Dermatitis

Posted by • December 15th, 2016

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For patients with moderate-to-severe atopic dermatitis, topical therapies have limited efficacy, and systemic treatments are associated with substantial toxic effects. Thus, there is an unmet need for effective and safe long-term medications for these patients. Simpson et al. reported the results of two phase 3 trials of dupilumab monotherapy (SOLO 1 and SOLO 2) in adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment or for whom topical treatment was medically inadvisable. In these placebo-controlled trials, dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, was effective in controlling the signs and symptoms of atopic dermatitis. A new Original Article explains.

Clinical Pearl

What are some of the features of atopic dermatitis?

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that is characterized by the up-regulation of type 2 immune responses (including those involving type 2 helper T cells), an impaired skin barrier, and increased Staphylococcus aureus colonization. In patients with moderate-to-severe atopic dermatitis, skin lesions can encompass a large body-surface area and are frequently accompanied by intense, persistent pruritus, which leads to sleep deprivation, symptoms of anxiety or depression, and a poor quality of life.

Clinical Pearl

• Why might dupilumab be an effective therapy for atopic dermatitis?

Dupilumab is a fully human monoclonal antibody that binds specifically to the shared alpha chain subunit of the interleukin-4 and interleukin-13 receptors, thereby inhibiting the signaling of interleukin-4 and interleukin-13, which are type 2 inflammatory cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis and asthma. In support of this premise, early-phase trials of dupilumab showed efficacy in patients with atopic dermatitis, those with asthma, and those with chronic sinusitis with nasal polyposis — all of which are conditions that have type 2 immunologic signatures.

Morning Report Questions

Q: Does dupilumab ameliorate the signs and symptoms of atopic dermatitis as compared to placebo?

A: In the SOLO trials, patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, weekly subcutaneous injections of dupilumab (300 mg) or placebo or the same dose of dupilumab every other week alternating with placebo. In SOLO 1 and SOLO 2, both dose regimens of dupilumab resulted in better results than placebo over 16 weeks of treatment across multiple outcome measures that reflected objective signs of atopic dermatitis, subjective symptoms (e.g., pruritus), important aspects of mental health (i.e., anxiety and depression), and quality of life. The mean efficacy results were similar for both dupilumab regimens. SOLO 1 and SOLO 2 were designed to provide replication of results, and patient populations and results were highly consistent in the two trials.

Q: What were some of the adverse events noted during the 16-week treatment period in the SOLO trials?

A: The most common adverse events in the two trials were exacerbations of atopic dermatitis, injection-site reactions, and nasopharyngitis. The incidence of nasopharyngitis was generally balanced across dupilumab and placebo groups. Exacerbations of atopic dermatitis and most types of skin infections were more common in the placebo groups. Injection-site reactions and conjunctivitis were more frequent in patients receiving dupilumab than in those receiving placebo.

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