The anti-IL-17A antibody secukinumab does not attenuate ozone-induced airway neutrophilia in healthy volunteers

Abstract

To the Editor: Within the lung the T-helper cell interleukin (IL)-17 (also referred to as IL-17A) is recognised as one of the principal cytokines that links the activation of T-lymphocytes to the chronic accumulation of neutrophils. It has been proposed that IL-17A is a relevant pharmacological target in inflammatory lung diseases with sustained mobilisation of neutrophils [1]. Secukinumab (AIN457; Novartis Healthcare Pvt. Ltd, Basel, Switzerland) is a recombinant high-affinity fully human monoclonal IL-17A antibody of the immunoglobulin (Ig)G1κ isotype, which binds to human IL-17A and neutralises the bioactivity of this cytokine [2]. Ozone exposure in healthy volunteers induces an acute and reproducible neutrophilic airway inflammation, which can be utilised as a pharmacological model to test anti-inflammatory drugs in early development [3–5]. We performed a single centre, phase II, double-blind, placebo-controlled, parallel-group study with an open label reference arm, investigating the ability of secukinumab to attenuate airway neutrophilia in induced sputum 24 h and 48 h following ozone exposure in healthy volunteers. Subjects underwent a 3 h ozone challenge, and induced sputum samples were collected 24 h and 48 h after the challenge. Subjects with an inflammatory response to ozone (as reflected by an increase in the total number of sputum neutrophils by at least 50% compared with the screening visit) were then randomised to receive either secukinumab (10 mg·kg−1 bodyweight) or placebo, in a double blind fashion administered as an infusion over 120 mins or to an open-label single-dose oral corticosteroid treatment (OCS, 50 mg) in the ratio of 2:1:1 (secukinumab:placebo:OCS). The secukinumab/placebo treatment period consisted of a single dosing visit on day 8 followed by an ozone challenge 1 week later on day 15 and subsequent …