Is Dupilumab Effective in AD Therapy for Patients for Whom Cyclosporine A Fails or Cannot Be Given?

Limitations of Cyclosporine A in Systemic AD Treatment

For patients suffering from AD with insufficient response to topical therapy or its intolerance, guidelines recommend the administration of systemic immunosuppressants. These, however, have variable efficacy and tolerability and show various adverse effects and undesirable drug interactions. The immunosuppressant cyclosporine A is approved in many European countries for the treatment of patients with severe AD who need systemic therapy. AD may require systemic therapy for a duration longer than one year; however, the long-term use of cyclosporine A is limited by the risk of adverse effects (hypertension, nephrotoxicity, headache, limb paresthesia, or fatigue) and contraindications based on the patient's health condition. Given the chronic nature of atopic dermatitis and the possible need for long-term pharmacotherapy, it is important to seek new drugs with a better benefit-risk ratio.

Indications and Uses of Dupilumab

Dupilumab is a fully human monoclonal antibody that selectively inhibits the signaling of interleukins 4 and 13. It is approved in the USA and the European Union for the treatment of adult patients with moderate to severe AD who are candidates for systemic therapy. Earlier studies have demonstrated the efficacy of dupilumab in the treatment of moderate to severe AD and have noted treatment-related adverse reactions, such as conjunctivitis and injection site reactions. Compared to placebo, there was no increased occurrence of infections or serious adverse effects. Dupilumab is also being evaluated in the treatment of other conditions such as asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis.

LIBERTY AD CAFÉ Trial

The double-blind, randomized, placebo-controlled phase III trial evaluated the efficacy and safety of dupilumab treatment with concomitant therapy of topical corticosteroids in adult patients with AD, in whom previous treatment with cyclosporine A was insufficient, intolerable, or medically inadvisable.

The study lasted 16 weeks and included 325 adult patients who were randomized 1 : 1 : 1. The first group received subcutaneous injections of 300 mg dupilumab once weekly, the second group 300 mg dupilumab once every 14 days, and the third group received a placebo. All participants also applied medium-potency topical corticosteroids from week −2 to week 16, with dosages reduced if lesions cleared or stopped due to adverse reactions to these agents.

Results

A total of 318 participants completed the study. A significantly higher proportion of patients in both dupilumab-treated groups achieved ≥ 75% improvement on the Eczema Area and Severity Index (EASI) scale compared to placebo (first group 59.1%, second group 62.6%, third group 29.6%; p < 0.001 compared to placebo for both comparisons). The first and second groups showed significant improvements in other clinical outcomes and AD symptoms, including pruritus, pain, sleep disturbances, anxiety, depression, and quality of life.

All groups exhibited comparable occurrences of adverse events (first group 69.1%, second group 72.0%, third group 69.4%) and serious adverse events (first group 1.8%, second group 1.9%, third group 1.9%). In the dupilumab-treated groups, there was a higher incidence of conjunctivitis compared to placebo, while the placebo group more frequently encountered skin infections. 

Conclusion

Dupilumab, in conjunction with concurrent topical corticosteroid therapy, significantly improved the symptoms of atopic dermatitis and quality of life in patients for whom cyclosporine A was either insufficient or not feasible. The study did not reveal new findings regarding the safety profile of dupilumab.

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Source: de Bruin-Weller M., Thaçi D., Smith C. H. et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol 2018; 178 (5): 1083−1101, doi: 10.1111/bjd.16156.