Rescue anakinra treatment for moderate asthma attacks

Asthma is a common and expensive chronic medical problem that incurs approximately $81.9 billion annually in health care costs, the bulk of which are attributable to emergency care visits and hospitalizations for asthma exacerbations. Most acute asthma exacerbations are triggered by respiratory viral infections and treated with systemic steroids as the standard of care to suppress inflammation. However, steroids do not target neutrophilic inflammation and mucus plugging, common problematic features of exacerbations. In addition, short courses of systemic steroids have multiple long-term adverse effects, exert broad immune suppression, and most importantly, failed to reduce hospitalizations due to viral exacerbations. To address the gap in steroid-sparing treatment options that can work quickly and effectively in asthma exacerbations, this pilot proposal will incorporate early intervention with the IL-1 receptor antagonist (IL-1RA), anakinra, as part of a home-based asthma action plan at the start of a moderate exacerbation with the goal of preventing severe exacerbations requiring systemic steroids. Anakinra is a recombinant IL-1RA with a fast onset of action and short half-life that is currently FDA-approved for the treatment of rheumatoid arthritis. Using a model of dust mite allergen inhalation in humans, we have shown that airway IL-1β associates with acute bronchoconstriction, eosinophil recruitment, and T2 cytokine production. We successfully and safely used anakinra pre-treatment to mitigate neutrophilic airway inflammation after environmental endotoxin challenge in healthy volunteers. We have also shown that IL-1RA treatment reduces rhinovirus-induced neutrophil chemoattractant release from airway epithelium and modulates mucin secretion without attenuating antiviral responses. We hypothesize that anakinra’s anti-inflammatory activity and fast onset of action without broad immunosuppressive effects make it an attractive candidate to test if using this steroid-sparing treatment during a moderate asthma exacerbation can prevent severe exacerbations. Our team has conducted hybrid decentralized observational studies and clinical trials in patients at high-risk for asthma exacerbations that have incorporated telehealth and digital health technologies and home-based sampling for inflammatory mediators. Leveraging this prior experience, the Anakinra Rescue Treatment for Moderate Asthma Attacks (ARTMA) pilot study will support the development of a multi-site hybrid decentralized double-blinded, randomized phase II clinical trial. The phase II trial will test if home-based administration of anakinra at the onset of a moderate exacerbation can prevent severe exacerbations requiring systemic corticosteroids and emergency care visits. We will determine the feasibility of recruitment, enrollment, and retention for a trial that requires self-administered injections (Aim 1); adherence to critical protocol operational tasks and rates of moderate exacerbations (Aim 2); and preliminary safety and efficacy of anakinra treatment during a moderate asthma exacerbation (Aim 3). This paradigm-shifting approach to asthma care has high potential to reduce morbidity and mortality and healthcare costs. Project Number: 1R34HL179910-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Michelle Hernandez | Institution: UNIV OF NORTH CAROLINA CHAPEL HILL, CHAPEL HILL, NC | Award Amount: $233,250 | Activity Code: R34 | Study Section: NHLBI Single-Site and Pilot Clinical Trials Study Section[SSPT (JA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R34HL17991001