Risankizumab treatment may not benefit severe asthma patients finds NEJM study

Interleukin-23 has been implicated in airway inflammation that is mediated by type 2 and types 17 cytokines. Whether targeting interleukin-23 in the treatment of asthma improves disease control and reduces airway inflammation is unclear.

A group of researchers conducted a phase 2a, multicenter, randomized, double-blind, placebo-controlled, 24-week, parallel-group trial to assess the efficacy and safety of risankizumab, an anti–interleukin-23p19 monoclonal antibody, in adults with severe asthma. Patients were assigned to receive 90 mg of risankizumab or placebo, administered subcutaneously once every 4 weeks. The primary endpoint was the time to first asthma worsening. Asthma worsening was defined as deterioration from baseline on 2 or more consecutive days; deterioration was considered to be a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in the number of puffs of rescue medication in a 24-hour period (equating to at least four additional puffs), a severe asthma exacerbation, or an increase of 0.75 or more points on the 5-item Asthma Control Questionnaire (ACQ-5; scores range from 0 to 6, with higher scores indicating less control). Secondary endpoints were the annualized rate of asthma worsening, the annualized rate of severe exacerbations, the ACQ-5 score, and the forced expiratory volume in 1 second. Exploratory endpoints were assessed with the use of sputum cytologic analysis and gene expression analysis, and safety was assessed.

The results of the study are as follows:

• A total of 105 patients received risankizumab and 109 received placebo.
• The clinical characteristics of the patients were similar in the two groups.
• The time to first asthma worsening was shorter with risankizumab than with placebo
• The rate ratio for annualized asthma worsening with risankizumab as compared with placebo was 1.49 and the rate ratio for severe exacerbations was 1.13 Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of the type 1 helper T and type 17 helper T transcription factors were down-regulated by risankizumab.
• No safety concerns were associated with risankizumab therapy.

Thus, the researchers concluded that Risankizumab treatment was not beneficial in severe asthma. The time to first asthma worsening was shorter and the annualized rate of asthma worsening was higher with risankizumab than with placebo.

Reference:

Risankizumab in Severe Asthma — A Phase 2a, Placebo-Controlled Trial by Christopher E. Brightling et al. published in the New England Journal of Medicine.

DOI: 10.1056/NEJMoa2030880