Interleukin-4/interleukin-13 versus interleukin-5: a comparison of molecular targets in biologic therapy for the treatment of severe asthma

Abstract

Purpose of review: Asthma is a chronic, inflammatory disorder of the airways caused by a complex interplay of various biologic mechanisms. Several monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways have been developed for the treatment of severe eosinophilic asthma. As individuals can display biomarkers and clinical features characteristic of several asthma phenotypes, selection of anoptimal biologic can be difficult.

Recent findings: Dupilumab, a monoclonal antibody that binds to the α subunit of the IL-4 receptor (IL-4Rα) and has been approved for the treatment of adults with severe atopic dermatitis, has been shown in recent phase 3 trials to also have significant clinical benefits in the asthmatic population irrespective of baseline eosinophil counts.

Summary: As monoclonal antibodies targeting either IL-4 or IL-13 cytokines individually have failed to demonstrate significant clinical benefits, biologics that target cytokine receptors may be more efficacious compared to those that target cytokines. Furthermore, inhibition of the IL-4/IL-13 signaling cascades may disrupt a broader Th2 inflammatory response compared to a more selective impairment of eosinophil proliferation and activity via blockage of the IL-5 pathway. Future research with independently funded, head-to-head trials of approved biologics is needed to elucidate a favorable therapeutic option.