Risankizumab in severe asthma: A Phase IIa, placebo-controlled study

Abstract

Interleukin (IL)-23 is implicated in many chronic inflammatory diseases, but its role in asthma is unclear.

We undertook a Phase II, randomized, double-blind, placebo-controlled, 24-week, parallel-group, multi-center study to assess the efficacy and safety of risankizumab, an IL23p19 monoclonal antibody, administered subcutaneously (90 mg every 4 weeks) in adults with severe asthma. The primary outcome was time-to-first asthma worsening defined as deterioration from baseline for ≥2 consecutive days (≥30% fall in morning peak expiratory flow or increase of ≥50% and at least 4 puffs in daily rescue medication), an increase in the five-question Asthma Control Questionnaire (ACQ5) ≥0.75 or a severe asthma exacerbation. Secondary endpoints included annualized rate of asthma worsening and severe exacerbations, ACQ5 and forced expiratory volume in 1 second (FEV1). Exploratory biomarkers including sputum cytology were evaluated.

105 patients received risankizumab and 109 received placebo. Clinical characteristics were similar between groups. Time-to-first asthma worsening significantly favored placebo (median 40 versus 86 days [hazard ratio 1.46; p=0.026]). Annualized asthma worsening was increased in risankizumab versus placebo (rate ratio 1.49 [0.22]; p=0.007) but was not different for severe exacerbation (rate ratio 1.13 [0.24]; p=0.56). The mean [SE] difference for ACQ5 was 0.15 [0.12] (p=0.20); pre- and post-bronchodilator FEV1 were -0.04L [0.05L] (p=0.44) and -0.07L [0.05L] (p=0.14), respectively. There were no significant changes in sputum cell differentials.

In conclusion, Risankizumab was not beneficial in severe asthma with time-to-first and rate of asthma worsening favoring placebo versus risankizumab.