In patients with moderate to severe asthma, the use of itepekimab monotherapy is associated with a lower incidence of events indicative of loss of asthma control, as well as with improved lung function. A phase 2, multicenter, randomized, placebo-controlled, parallel-group, proof-of-concept trial (ClinicalTrials.gov identifier: NCT03387852) was conducted at 70 sites. Results of the analysis were published in the New England Journal of Medicine.
The investigators sought to explore the efficacy and safety of the monoclonal antibody itepekimab, which targets interleukin-33 (IL-33), both as monotherapy and combined with dupilumab in patients with asthma. Researchers randomly assigned adult patients with moderate to severe asthma who were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to 1 of 4 treatment regimens: (1) subcutaneous (SC) itepekimab 300 mg; (2) SC combination therapy with itepekimab 300 mg plus dupilumab 300 mg; (3) SC dupilumab 300 mg; or (4) SC placebo every
2 weeks for at least 4 weeks. Following randomization, LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered during weeks 6 through 9.
The primary study endpoint was an event indicative of loss of asthma control, which was evaluated in the itepekimab arm and in the combination arm and then compared with the placebo arm. Additional outcomes included lung function (as measured by peak expiratory volume in 1 second [FEV1]), quality of life (QoL), asthma control, safety, and type 2 biomarkers. The trial included a 4-week screening period, which was followed by a 12-week intervention period (incorporating the withdrawal of background medication) and a 20-week postintervention follow-up period.
A total of 296 participants were enrolled in the study and underwent randomization; 73 received itepekimab, 74 received itepekimab plus dupilumab, 75 received dupilumab, and 74 received placebo. Eligible patients were between 18 and 70 years of age, had physician-diagnosed asthma for at least 12 months based on Global Initiative for Asthma (GINA) 2017 guidelines, and had been receiving medium- to high-dose inhaled glucocorticoids combined with a LABA for at least 3 months.
The study found that at 12 weeks, an event indicative of loss of asthma control was reported among 22% of those in the itepekimab group, 27% of those in the combination therapy group, and 19% of those in the dupilumab group, compared with 41% of individuals in the placebo group. Values in the 3 treatment arms compared with the placebo arm were as follows: itepekimab group (odds ratio [OR], 0.42; 95% CI, 0.20-0.88; P =.02); combination group (OR, 0.52; 95% CI, 0.26-1.06; P =.07; dupilumab group (OR, 0.33; 95% CI, 0.15-0.70; P value not applicable).
When compared with placebo, FEV1 prior to bronchodilator use increased with itepekimab and dupilumab monotherapy, but not with combination therapy. When compared with placebo, itepekimab therapy was associated with a greater reduction in mean blood eosinophil counts, as well as with improved control of asthma and QoL. Rates of adverse events were similar across the 4 treatment arms.
The investigators concluded that IL-33 blockade with itepekimab demonstrates a role for the agent in the pathogenesis of exacerbations and airflow limitations among patients with asthma.
Disclosure: Some study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N Engl J Med. 2021;385(18):1656-1668. doi:10.1056/NEJMoa2024257