RATIONALE: IL-17 signaling has been implicated in development and persistence of 
asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be 
beneficial in asthma treatment.
OBJECTIVES: To determine efficacy and safety of brodalumab, a human anti-IL-17 
receptor A monoclonal antibody, in subjects with inadequately controlled 
moderate to severe asthma taking regular inhaled corticosteroids.
METHODS: Three hundred two subjects were randomized to brodalumab (140, 210, or 
280 mg) or placebo. Primary endpoint was change in Asthma Control Questionnaire 
(ACQ) score from baseline to Week 12. Secondary endpoints included FEV1, symptom 
scores, and symptom-free days. Prespecified subgroup analyses were conducted to 
identify potential responsive subpopulations. Analyses included randomized 
subjects receiving one or more doses of investigational product using 
last-observation-carried-forward imputation.
MEASUREMENTS AND MAIN RESULTS: Demographics and baseline characteristics were 
generally balanced among groups (n = 302; n = 226 brodalumab). For the overall 
study population, no treatment differences were observed. Nine prespecified 
subgroups were examined without corrections for multiple testing. In only the 
high-reversibility subgroup (post-bronchodilator FEV1 improvement ≥ 20%; n = 
112) was an ACQ change with nominal significance noted; ACQ responses were 
nominally significant in the 210-mg group (estimated treatment difference, 0.53) 
but not significant in the higher 280-mg group (estimated treatment difference, 
0.38). Adverse events, generally balanced among groups, were most commonly 
asthma, upper respiratory tract infection, and injection site reaction.
CONCLUSIONS: Inhibition of IL-17 receptor A did not produce a treatment effect 
in subjects with asthma. The results of the high-reversibility subgroup analysis 
are of uncertain significance, requiring further study of brodalumab in this 
asthma subpopulation. Clinical trial registered with www.clinicaltrials.gov 
(NCT01199289).