Risankizumab is not beneficial for the treatment of severe asthma, according to findings of a phase 2a study ClinicalTrials.gov Identifier: NCT02443298) published in the New England Journal of Medicine.
While interleukin-23 has been implicated in airway inflammation that is mediated by type 2 and type 17 cytokines, it is unclear whether targeting interleukin-23 actually improves disease control and reduces airway inflammation in asthma. Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23 that was developed to treat adults with severe persistent asthma.
Researchers conducted a multicenter, randomized, double-blind, parallel-group trial to assess the efficacy and safety of risankizumab in adults with severe asthma. Over 24 weeks, 105 patients were administered 90 mg of risankizumab subcutaneously every 4 weeks while 109 patients received placebo.
The researchers found that the time to the first asthma worsening was shorter with risankizumab than with placebo (median, 40 days vs. 86 days; P =.03). 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. Lung function, 5-item Asthma Control Questionnaire scores, and the severe asthma exacerbation rates were similar in the 2 groups. Risankizumab therapy did not affect sputum cell counts, but it did attenuate the sputum interleukin-23 gene set and gene pathways associated with activation of cytotoxic T cells and natural killer cells and the Th17 transcription factor, RORC, and the Th1 transcription factor, TBX21.
These findings support that risankizumab exerted a biologic effect on airway immunity, which may have contributed to the poor clinical outcome. In addition, no safety issues were associated with risankizumab therapy.
The researchers concluded that, “Risankizumab treatment was not beneficial in severe asthma.” They added, “The time to the first asthma worsening was shorter and the annualized rate of asthma worsening was higher with risankizumab than with placebo.”
Disclosure: This research was supported by AbbVie and Boehringer Ingelheim. Please see the original reference for a full list of disclosures.
Brightling CE, Nair P, Cousins DJ, Louis R, Singh D. Risankizumab in severe asthma — a phase 2a, placebo-controlled trial. N Engl J Med. 2021;385:1669-79. doi:10.1056/NEJMoa2030880