Dupilumab, brand name Dupixent, is a human IgG4 monoclonal antibody that was initially approved by the FDA in March of 2017. The initial approval was for the treatment of atopic dermatitis for patients with moderate-to-severe disease that is not adequately controlled with topical prescription therapies. Since its initial approval, it has been approved to be used in patients aged 6-11 years with atopic dermatitis as well as for the treatment of moderate-to-severe asthma for patients 12 years or older with an eosinophilic phenotype or who require an oral corticosteroid in their treatment.
Atopic dermatitis is a chronic skin condition that is characterized by a disturbed skin barrier and immune-mediated responses to environmental antigens. Th2 cytokines, interleukin-4 and interleukin-14, have been believed to play a role in the disease of atopic dermatitis but the clinical effect of blocking these interleukins had not been tested until the introduction of dupilumab. Dupilumab blocks signaling from both interleukins and shows positive response in atopic dermatitis patients. In addition, blockage of these Th2 interleukins showed efficacy in patients with moderate-to-severe asthma identifying that the blockage could aid in other Th2 related disease states. In a pivotal study for the approval of dupilumab in atopic dermatitis, the treatment was studied in two, 4-week monotherapy trials, a 12-week monotherapy trial, and a 4-week combination trial with topical glucocorticoids. Across all four studies, a positive correlation was found highlighting the significance of Th2 cytokines in the pathophysiology of atopic dermatitis. The blockade of these interleukins provided a reduction in skin lesions, as well as a decrease in pruritus which is a major complaint in patients with atopic dermatitis. Within the study groups, it was noted that the patients receiving placebo had higher rates of skin infection, indicating dupilumab aids in improving the skin barrier function.
As previously mentioned, Th2 cytokines play a role in the pathogenesis of asthma. Asthma presents in different phenotypes, meaning that the pathological process that produces asthma can slightly vary among patients. The inflammatory processes with these specific cytokines are present in about half of patients who are living with asthma. Despite several types of treatments on the market, 10-20% of patients with this diagnosis are not adequately controlled. The Th2 cytokines that are present in patients with atopic dermatitis are also present in patients with asthma but are signaled through different receptors. In one study, dupilumab was able to reduce asthma-exacerbation events by 87% compared to placebo.3. Dupilumab shows positive objective and subjective endpoints when it was added to previous mainstay therapies such as inhaled glucocorticoids and long-acting beta agonists. Compared to other monoclonal antibodies studied in asthma patients, such as lebrikizumab and tralokinumab, dupilumab also targets interleukin-4 and provides a reduction in asthma symptoms, beta-agonist drug use, and an increase in quality of life. These other treatments only improved lung function. Dupilumab is still in the pipeline to expand its indications to different age groups within its currently approved indications as well as a brand-new indication for the treatment of patients with peanut or grass allergies.
1. Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139. doi:10.1056/NEJMoa1314768
2. Barry K, Gorelik D. Dupilumab (Dupixent) for Asthma. Am Fam Physician. 2020;101(4):244-245.
3. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455-2466. doi:10.1056/NEJMoa1304048