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.

Important roles of CD32 in promoting suppression of IL-4 induced immune responses by a novel anti-IL-4Rα therapeutic antibody

“…Asthma affects an estimated 241 million children and adults worldwide, of which approximately 5-10% is severe asthma. 1,2 Interleukin-4 (IL-4) and interleukin-13 (IL-13) are major T-helper type 2 (Th2) cytokines that play important roles in the pathogenesis of atopic and eosinophilic asthma. IL-4 plays a key role in regulating naïve T cells to develop into Th2-like cells capable of producing cytokines such as IL-4, IL-13, and IL-5.…”

Combined administration of anti‐IL‐13 and anti‐IL‐17A at individually sub‐therapeutic doses limits asthma‐like symptoms in a mouse model of Th2/Th17 high asthma

“…Finally, IL‐13 is considered a key effector molecule that can induce many of the pathological changes observed in the asthmatic airway, including smooth muscle hypertrophy, goblet cell hyperplasia, airway remodelling, and increased airway hyperresponsiveness . Based on the expected primacy of these Th2 cytokines in the pathogenesis of allergic asthma, blockade of IL‐4, IL‐5, and IL‐13 (or their receptors) is actively being investigated for their therapeutic efficacy in the treatment of allergic asthma …”

Indirect Comparison of Dupilumab and Mepolizumab Treatments for Uncontrolled Eosinophilic Asthma

“…The plausibility of these results can be explained by looking into the molecular biological mechanisms of dupilumab. Type 2 T helper Th2 cytokines, such as IL-4 and IL-13, have a large pathogenic impact on the eosinophilic and allergic in ammatory process in approximately 50% of patients with uncontrolled or severe asthma 18 . The ndings of the present study strongly support the use of dupilumab as an effective option for patients with uncontrolled eosinophilic asthma.…”

“…Several phase 2 or 3 studies have revealed that new therapeutic mAbs, including anti-IL-13, anti-IL-4/13, and anti-IL-5 mAbs, significantly improve pulmonary function and the incidence of asthma exacerbation compared with the placebo in uncontrolled eosinophilic asthma [5][6][7][8] . Moreover, the frequencies of drug-related adverse events were similar between these therapeutic agents and the placebo.…”