A review of dupilumab in the treatment of atopic diseases

Abstract

Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.

Mechanisms of Dupilumab

“…Dupilumab is an IgG4 human monoclonal antibody (mAb) that binds IL‐4Ra . Dupilumab inhibits IL‐4R signalling induced by both IL‐4 and IL‐13, and down‐regulates TH2 inflammation in a variety of allergic disorders, including atopic dermatitis, asthma and possibly other allergic diseases .…”

“…Dupilumab has been approved by the food and drug administration (FDA) in the united states for the treatment of moderate‐to‐severe atopic dermatitis in uncontrolled patients . In a 16 week, randomized, placebo‐controlled phase III study, the efficacy of Dupilumab in treating severe AD was investigated.…”

Advances and novel developments in mechanisms of allergic inflammation

“…The number of potentially disease‐triggering Th2‐biased Treg cells was further significantly decreased by IL‐4 and IL‐13 antagonist IL‐4 mutein (IL‐4M) treatment even 2 weeks later 24 . As shown in Table 1, dupilumab, a fully humanized IgG4 monoclonal antibody targeting the IL‐4Rα subunit, 25,26 inhibits IL‐4 signalling by binding to IL‐4Rα, and/or inhibit the recruitment of γc to IL‐4Rα chain and/or inhibits the recruitment of the IL‐4Rα to IL‐13Rα1, and therefore downregulates Th2 inflammation in allergic disorders 27 . The suppression of allergic tissue inflammation by dupilumab, such as seen in eczema, would suggest inhibition of IL‐4R type II receptor signalling 28 .…”

Resolution of inflammation: from basic concepts to clinical application

“…In multiple sclerosis, the CD52 inhibitor alemtuzumab has been tested for clinical therapy [65]. Furthermore, blockers of IL-4, IL-5, or IL-13 signalling such as benralizumab, mepolizumab, or dupilumab [66][67][68][69][70] have been used in patients with allergic asthma. In addition, monoclonal antibodies targeting IL-12/IL-23 p40 (e.g., ustekinumab in psoriasis and Crohn's disease [71][72][73]) or IL-23 p19 (e.g., risankizumab, guselkumab, tildrakizumab in psoriasis [74,75]) have reached clinical therapy in a variety of inflammatory disorders.…”