1-Minute Summary: Dupilumab Improves Clinical Outcomes in Patients with Asthma and Perennial Allergic Rhinitis

Expert Name
Dr William W. Busse
Expert Affiliation
University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Expert Google Scholar or Orcid Url
https://orcid.org/0000-0003-2591-4696
Journal
Annals of Allergy, Asthma and Immunology
DOI
10.1016/j.anai.2020.05.026

Busse WW, et al. Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis [published online ahead of print, 2020 May 28]. Ann Allergy Asthma Immunol. 2020;S1081-1206(20)30389-6.

In this post-hoc analysis of the phase 3 LIBERTY ASTHMA QUEST trial, the effect of dupilumab on comorbid perennial allergic rhinitis (PAR) was investigated. PAR is often associated with sensitisation to indoor allergens and significantly contributes to disease burden in asthma patients [1-2]. Symptoms of PAR typically persist despite available treatment [3]. The immunopathologic and functional features of PAR and asthma show similarities, including manifestations of type 2 inflammation [4,5]. Key drivers of type 2 inflammatory processes are interleukin (IL)-4 and IL-13, both of which play a role in asthma and PAR [4-10]. The shared receptor for IL-4 and IL-13 is blocked by dupilumab, inhibiting signalling by both cytokines [11]. In the current phase 3 trial dupilumab reduced symptoms in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline [12]. The aim of the current study was to assess whether dupilumab is also efficaceous in patients with comorbid PAR.

Figure. Effect of dupilumab on annualised severe exacerbation rates in patients with comorbid PAR (A), baseline blood eosinophils ≥150 cells/μL (B). *P<0.05, **P<0.01, vs matched placebo. CI, confidence interval; FeNO, fractional exhaled nitric oxide levels; ITT, intent to treat; q2w, every two weeks.

Of 1,902 total patients from the phase 3 trial, 814 (42.8%) had comorbid PAR and were included in the post-hoc analysis. Dupilumab 200 and 300 mg q2w versus placebo reduced severe asthma exacerbation rates by 32.2% (P=0.04) and 34.6% (P=0.01) (see Figure), and improved forced expiratory volume in 1 second (FEV1) at Week 12 by 0.14 L (P=0.002) and 0.18 L (P<0.001); higher efficacy was observed in patients with elevated baseline blood eosinophils (≥300 cells/μL) and fractional exhaled nitric oxide (FeNO). Dupilumab improved asthma control as measured with ACQ-5 and health-related quality of life (QoL), as measured by RQLQ(s)+12 scores. Type 2 inflammatory biomarkers were reduced, including perennial allergen-specific immunoglobulin E, FeNO, and CCL17. Dupilumab was generally well tolerated.

With its inhibitory effects on the type 2 inflammatory processes underlying both asthma and PAR, dupilumab may have a role in managing both of these comorbid conditions simultaneously.

References

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  9. Swain SL, et al. IL-4 directs the development of Th2- like helper effectors. J Immunol 1990;145:3796-3806.
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  11. Gandhi NA, et al. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 2017;13:425-437.
  12. Castro M, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 2018;378:2486-2496.

 

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