Dupilumab in the management of moderate-to-severe asthma: the data so far

Abstract

Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs). It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future.

Keywords: asthma; dupilumab; interleukin-13; interleukin-4; monoclonal antibodies; treatment.

Figure 1

Inflammatory and structural changes in asthmatic airways promoted by IL-4 and IL-13. Abbreviations: ASM, airway smooth muscle cells; ILC2, type 2 innate lymphoid cells; iNOS, inducible nitric oxide synthase; LTs, leukotrienes.

Figure 2

Activation of a heterodimeric receptor complex comprised of the IL-13 receptor α1 subunit (IL-13Rα1) and the IL-4 receptor α subunit (IL-4α) by IL-13 and IL-4. Abbreviations: IL, interleukin; JAK, Janus kinase; STAT, signal transducer and activator of transcription; Tyk, tyrosine kinase.