Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis

Abstract

Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma.Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4.Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events.Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

“…Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL-4Rα chain, which has been officially approved for several type 2 inflammatory diseases, including moderate to severe atopic dermatitis (AD) [90][91][92], moderate-to-severe eosinophilic or oral steroid-dependent asthma [93,94], inadequately controlled CRSwNP [95,96] and aspirin-exacerbated respiratory disease [97,98]. Since the first proof-of-concept study of dupilumab was reported in 2016, 25 clinical trials have been conducted on CRSwNP worldwide, which have demonstrated broad efficacy in CRSwNP management [99].…”

Biologic therapies for severe asthma with persistent type 2 inflammation

“…Robust clinical trial evidence has demonstrated that for appropriately selected patients, the addition of a biologic asthma therapy to a patient's existing moderate-dose ICS and LABA regimen results in significant reductions in exacerbations and use of oral corticosteroids, and improved asthma symptom control and quality of life, though there are only modest improvements in lung function. [29][30][31][32][33] Table 1 provides a comparison of biologic therapies for severe asthma, including efficacy data.…”

Advances in the Relationship between Respiratory Viruses and Asthma

“…An IL-4Rα targeted biologic agent, blocking the effects of IL-4 and IL-13, contributes to the reduction in different markers from T2 inflammation, including FENO, IgE, periostin, and eotaxin-3, among others. Dupilumab could also improve antiviral immune response in patients with severe T2 asthma on account of IL-4 and IL-13 by damaging the production of viral-induced IFN that expresses TLR3 [4,101].…”