Risankizumab in Severe Asthma: A Phase IIa, Placebo-Controlled Study

Christopher E Brightling, Parameswaran Nair, David J. Cousins, Renaud Louis, Dave Singh

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Background: Interleukin (IL)-23 is implicated in T2- and T17-mediated airway inflammation, supporting a role in asthma. Methods: We undertook a Phase II, randomized, double-blind, placebo-controlled, 24-week, parallel-group, multicenter trial to assess the efficacy and safety of risankizumab, an IL23p19 monoclonal antibody, administered subcutaneously (90 mg 4 weekly) 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 and
exploratory biomarkers included annualized rate of asthma worsening and severe exacerbations, ACQ5 and forced expiratory volume in 1 second (FEV1), sputum cytology and gene expression.
Results: 105 patients received risankizumab and 109 received placebo. Clinical characteristics were similar between groups. Time-to-first asthma worsening favored placebo (median 40 versus
36 86 days [hazard ratio 1.46 (95% confidence interval [CI]: 1.05–2.04); p=0.026]). The rate ratio of the annualized asthma worsening in risankizumab versus placebo was 1.49 (95% CI: 1.12–1.99)
and the hazard ratio for severe exacerbation was 1.13 (95% CI: 0.75–1.70). Sputum transcriptomic pathway analysis identified that genes involved in natural killer and cytotoxic T-cell activation and Th1 and Th17 transcription factors were downregulated by risankizumab. No safety concerns were identified for risankizumab versus placebo.
Conclusions: Risankizumab was not beneficial in severe asthma, with time-to-first and rate of asthma worsening favoring placebo versus risankizumab.
Original languageEnglish
JournalThe New England Journal of Medicine
Publication statusAccepted/In press - 30 Aug 2021


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