Type 2 asthma managed by dupilumab, despite atopic comorbidities

The phase 3 Liberty Asthma VOYAGE trial reported that dupilumab reduced severe asthma exacerbation rates and also improved overall lung function in children with moderate-to-severe asthma, independent of the presence of atopic comorbidities, including chronic rhinosinusitis, nasal polyps, or eosinophilic oesophagitis.

A new post hoc analysis of the Evaluation of Dupilumab in Children with Uncontrolled Asthma trial (Liberty Asthma VOYAGE, NCT02948959) which was presented by Prof. Theresa Guilbert (University of Cincinnati, OH, USA) took a look at the effect of dupilumab, a monoclonal antibody that blocks 2 primary drivers of type 2 inflammation (IL-4 and IL-13), on comorbid atopic disorders and type 2 inflammation in that cohort. The main Liberty Asthma VOYAGE trail evaluated the efficacy of dupilumab 100/200 mg every 2 weeks compared with placebo in children aged 6 to 11 years with uncontrolled persistent asthma, and reported positive effects on severe asthma exacerbations in December 2021 [2].

For the current post hoc analysis, 408 participants treated with dupilumab or placebo were stratified by their burden of comorbid disease, into groups without any comorbid disease (dupilumab n=33; placebo n=28), with 1 comorbid phenotype (dupilumab n=91; placebo n=41), or with >1 ongoing comorbid disease (dupilumab n=149; placebo n=66). Participants were evaluated over the course of a 52-week treatment period. Comorbid diseases were self-reported at baseline and included atopic dermatitis, allergic conjunctivitis, allergic rhinitis, chronic rhinosinusitis (chronic rhinitis or chronic sinusitis), nasal polyposis, eosinophilic oesophagitis, food allergy, and hives. Participants were assessed via the annualised rate of severe asthma exacerbations and lung function, measured by change from baseline in percent predicted prebronchodilator forced expiratory volume in 1 second (FEV₁pp).

The results indicated that severe asthma exacerbations were reduced among patients treated with dupilumab, compared with those treated with placebo, despite whether they presented with no comorbid disease (relative risk [RR] 0.284; 95% CI 0.072–1.117; D-71.6%; P=0.07), 1 ongoing comorbid disease (RR 0.980; 95% CI 0.438–2.194; D-2%; P=0.96), or >1 comorbid disease (RR 0.315; 95% CI 0.207–0.479; D -68.5%; P<0.0001).

At 12 weeks, lung function improved most in patients with >1 atopic comorbidity treated with dupilumab; pre-bronchodilator FEV₁pp after 12 weeks was significantly improved by dupilumab treatment (1 comorbid disease: least square mean difference [LSMD] 5.37; 95% CI -0.18 to 10.93; P=0.058; >1 comorbid disease: LSMD 5.34; 95% CI 1.58–9.11; P=0.006), although no difference in changes from baseline in pre-bronchodilator FEV₁pp were observed among patients with no atopic comorbidities (LSMD -0.96; 95% CI -9.04 to 7.11; P=0.812).

However, even for patients without any comorbid type 2 phenotype, after 52 weeks, dupilumab was associated with improvement in the change from baseline in pre-bronchodilator FEV₁pp for all patients compared with placebo: no comorbidities (LSMD 7.86; 95% CI 0.21–15.51; P=0.044), 1 comorbid disease (LSMD 5.87; 95% CI -0.64 to 12.38; P=0.077), or >1 comorbid disease (LSMD 7.26; 95% CI 3.17–11.36; P<0.001).

Prof. Guilbert concluded that dupilumab reduced severe exacerbation rates and by the end of treatment, had improved the percent predicted pre-bronchodilator FEV₁ in children aged 6 to 11 years with uncontrolled, moderate to severe asthma, in patients with or without atopic comorbidities.

1. Guilbert TW, et al. Efficacy of dupilumab in pediatric patients with uncontrolled, moderate-to-severe asthma with and without ongoing atopic comorbid disease: LIBERTY ASTHMA VOYAGE Study. Session A2, ATS International Conference 2022, San Francisco, CA, USA, 13–18 May.


2. Bacharier LB, et al. N Engl J Med. 2021 Dec 9;385(24):2230–2240.

 

 

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Posted on 18 May, 2022