Risankizumab in Severe Asthma - A Phase 2a, Placebo-Controlled Trial.

Area of Science:

• Immunology
• Pulmonology
• Clinical Trials

Background:

• Interleukin-23 (IL-23) is implicated in airway inflammation via type 2 and type 17 cytokines.
• The efficacy of IL-23 targeting in severe asthma management remains uncertain.

Purpose of the Study:

• To assess the efficacy and safety of risankizumab, an anti-IL-23p19 monoclonal antibody, in adults with severe asthma.
• To evaluate the impact of risankizumab on disease control and airway inflammation.

Main Methods:

• A phase 2a, randomized, double-blind, placebo-controlled trial involving 214 adults with severe asthma.
• Patients received subcutaneous risankizumab (90 mg) or placebo every 4 weeks for 24 weeks.
• Primary endpoint: time to first asthma worsening; secondary endpoints included exacerbation rates and Asthma Control Questionnaire (ACQ-5) scores.

Main Results:

• The time to first asthma worsening was shorter with risankizumab (median 40 days) compared to placebo (median 86 days).
• The annualized rate of asthma worsening was higher with risankizumab (rate ratio 1.49) versus placebo.
• Risankizumab down-regulated genes associated with natural killer cells, cytotoxic T cells, and type 1/17 helper T cell activation; no safety concerns were noted.

Conclusions:

• Risankizumab treatment did not demonstrate benefit in severe asthma.
• The study indicated a potential for increased asthma worsening with risankizumab compared to placebo.
• Further research may be needed to clarify the role of IL-23 inhibition in severe asthma.