Dupilumab is a novel monoclonal antibody recently approved in the USA for the treatment of adult patients with moderate-to-severe atopic dermatitis. A phase III clinical study comparing dupilumab injection with placebo demonstrates promising clinical results for patients with dermatitis.
Atopic dermatitis is chronic inflammatory skin disease, characterized by red, itchy lesions. Dermatitis occurs as results of abnormal immune function at the skin barrier, resulting in infiltration of T lymphocytes to the dermis and a reaction that causes inflammation, redness and lesions. Current treatments aimed at reducing inflammation are limited and include recommendations for general skin care and use of moisturizing agents. Topical corticosteroids are applied as a next step if general skin care isn’t effective. Corticosteroids are natural inflammatory reducers and are effective treatment for patients with dermatitis, however, due to their adverse events profile, the medical guidelines recommend limiting treatments with high-potency topical corticosteroids to short periods and for acute cases of atopic dermatitis. Therefore, patients with moderate-to-severe dermatitis have especially limited treatment options and there is a need for novel safe and effective therapies.
Dupilumab is a human monoclonal antibody that binds to interleukin-4 and interleukin-13 receptors expressed on cell surface. By blocking interleukin receptors, it inhibits binding of inflammatory cytokines thereby blocking cytokine-mediated signaling and reducing inflammation in numerous allergic reactions ranging from asthma to atopic dermatitis.
In a placebo-controlled 1 year randomized, double blinded clinical study reported in The Lancet, dupilumab treatment was associated with substantial improvement in patients with moderate-to-severe dermatitis at 16 and 52 weeks compared to placebo group. All treatment groups also received moderated potency corticosteroids.
A total of 740 patients were enrolled in the study during 2014-2015 at 161 clinical sites. In addition to topical corticosteroids, 319 patients were randomly assigned to receive a 300 mg dupilumab injection once a week, 106 patients to receive a 300 mg dupilumab injection once every two weeks, and 315 to receive placebo. Placebo was provided in identical syringes and the study was blinded to all participants (patients, medical personnel, investigators). Patients suffering from moderate-to-severe dermatitis for 3 years and more, with documented inadequate response to topical corticosteroids, an Investigator’s Global Assessment (IGA) score of 3 or higher and an Eczema Area and Severity Index (EASI) of 16 or higher at baseline were eligible for enrolment.
During the study patients were assessed for two endpoints (targets achieved during treatment) after 16 weeks of treatment: reduction in dermatitis area to clear or almost clear skin, indicated by a 0 or 1 IGA score on a 0-4 scale and proportion of patients that achieved 75% improvement in EASI (score for assessing dermatitis levels) compared to baseline.
Both dose regimens with dupilumab plus topical treatment improved dermatitis lesions as assessed by the endpoint measurements described above. The improvement was sustained over 52 weeks of treatment. Additionally, patients receiving dupilumab reported improvement in anxiety and depression and overall quality of life scores. At week 16, 39% of patients who received dupilumab once a week, or every two weeks achieved clear or almost clear skin (IGA score of 0 or 1), compared to 12% in the placebo group (p<0.0001). Over 60% of patients demonstrated 75% improvement in EASI scale compared to 23% of patients in the placebo group (p<0.0001). Week 52 results were similar.
The most common adverse events in patients treated with dupilumab were injection site reactions and conjunctivitis. Overall, the study results demonstrate a significant benefit of adding dupilumab to medium or low-potency topical corticosteroids to control dermatitis symptoms.
In March 2017, Dupilumab, brand name DUPIXENT, was approved by the FDA for adult patients with moderate-to-severe atopic dermatitis. The FDA granted the approval of Dupixent to Regeneron Pharmaceuticals, Inc.
Written By: Bella Groisman, PhD