Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils

Guy Brusselle,Matthew Germinaro,Sivan Weiss,James Zangrilli

doi:10.1016/j.pupt.2017.01.011

Abstract

IntroductionAsthma with adult onset and elevated blood eosinophils is a difficult-to-treat subgroup. This post hoc analysis evaluated reslizumab, an anti-interleukin-5 monoclonal antibody, in patients with late-onset eosinophilic asthma. MethodsData from two 52-week placebo-controlled trials of reslizumab IV 3 mg/kg every 4 weeks in patients aged 12–75 years with inadequately controlled asthma, ≥1 asthma exacerbation within 12 months, and screening blood eosinophils ≥400/μL (NCT01287039/NCT01285323) were stratified by age of asthma onset (<40 or ≥40 years). Annual clinical asthma exacerbation rates, change in lung function, and patient-reported outcomes were analyzed. Results273 patients with late-onset asthma (placebo, n = 130; reslizumab, n = 143) and 658 with early-onset asthma (placebo, n = 336; reslizumab, n = 322) were included. Baseline demographics were similar between groups. The interaction between age at onset of asthma and effect of reslizumab on asthma exacerbations was statistically significant (p = 0.0083). Compared with placebo, reslizumab produced a 75% relative reduction in asthma exacerbations in patients with late-onset asthma (rate ratio [RR] 0.25; 95% confidence interval [CI], 0.16, 0.40), substantially larger than the reduction in earlier onset patients (RR 0.58; 95% CI, 0.44, 0.76). Similar findings were observed for other measures of asthma, including forced expiratory volume in 1 s (FEV1). The adverse event profile of reslizumab was similar in patients with early- or late-onset asthma. ConclusionsCompared with placebo, reslizumab produced larger reductions in asthma exacerbations and larger improvements in lung function in patients with late versus early-onset asthma.

Highlights

Asthma with adult onset and elevated blood eosinophils is a difficult-to-treat subgroup
The defining age for late onset (LO) of asthma varies in the literature, with early onset typically used to describe symptoms developing during childhood and LO asthma defined as asthma with onset in adulthood [11,12]
The aim of this post hoc analysis of the pooled data from two replicate, phase 3 studies of reslizumab (3 mg/kg IV every 4 weeks (Q4W)) in uncontrolled eosinophilic asthma was to assess the comparative efficacy of reslizumab in patients with LO asthma versus early-onset asthma

Summary

Introduction

Asthma with adult onset and elevated blood eosinophils is a difficult-to-treat subgroup. This post hoc analysis evaluated reslizumab, an anti-interleukin-5 monoclonal antibody, in patients with late-onset eosinophilic asthma. Conclusions: Compared with placebo, reslizumab produced larger reductions in asthma exacerbations and larger improvements in lung function in patients with late versus early-onset asthma. Asthma developing for the first time in adulthood (late onset [LO]) represents a difficult-to-treat subgroup of the severe asthma population, and is associated with a distinctive biology and phenotypic characteristics compared with asthma that develops in childhood [early onset]) [1e3]. Treatment with reslizumab improved pulmonary function, patient-reported asthma control, symptoms and quality of life measures [4]

Methods

Results

Conclusion