This article is part of Pulmonology Advisor‘s coverage of the ACAAI 2018 meeting, taking place in Seattle, Washington. Our staff will report on medical research related to allergy, asthma, and more conducted by experts in the field. Check back regularly for more news from ACAAI 2018.
SEATTLE — Asthma control, as measured by the 5-item Asthma Control Questionnaire (ACQ-5), was significantly improved by dupilumab, regardless of exacerbation history, according to research presented at the 2018 Annual Scientific Meeting of the American College of Allergy, Asthma, and Immunology, held November 15th through November 19th in Seattle.
Treatment with the fully human anti-interleukin-4 receptor monoclonal antibody dupilumab inhibits anti-interleukin-4 and 13 signaling pathways, which are key drivers of inflammation. Dupilumab is currently approved for treatment of moderate to severe atopic dermatitis, and researchers in this phase 3 study (Liberty Asthma Quest; ClinicalTrials.gov Identifier: NCT02414854) investigated the effects of dupilumab vs matched placebo in patients with moderate to severe uncontrolled asthma.
To do this, they conducted a post hoc analysis using ACQ-5 scores in the patient subgroups who had at least 1, 2, or 3 severe asthma exacerbations in the prior year. The primary endpoints in the study were change from baseline in pre-bronchodilator FEV1 at week 12 and annualized rate of severe exacerbations during the 52-week treatment period. Change from baseline in ACQ-5 during the 52 weeks in the specific patient groups were also assessed.
Compared with placebo, treatment with dupilumab 200 mg and 300 mg significantly reduced annualized severe exacerbation rates by 48% and 46% (P for both <.001) in the overall group. Also, pre-bronchodilator FEV1 at week 12 was improved by 0.32 L and 0.34 L with dupilumab 200 mg and 300 mg, respectively (difference vs placebo 0.14 L and 0.13 L; P for both <.001) in the overall population.
Better asthma control, as indicated by lower mean scores on the ACQ-5, were seen in both dupilumab groups vs placebo in patients with severe exacerbation events. At week 2, scores were significantly reduced by −0.34 (95% CI, −0.46 to −0.22), −0.36 (95% CI, −0.53 to −0.19), and −0.48 (95% CI, −0.76 to −0.21) in the dupilumab 200 mg group vs matched placebo in patients with ≥1, ≥2, and ≥3 exacerbation events, respectively (P for all <.001). For dupilumab 300 mg, the scores were significantly reduced by −0.31 (95% CI, −0.42 to −0.19), −0.27 (95% CI, −0.44 to −0.11), and −0.47 (95% CI, −0.73 to −0.21), respectively.
These improvements in ACQ-5 scores were sustained at week 52 despite exacerbation history (P <.05 dupilumab vs placebo).
Regarding safety, the occurrence of treatment-emergent adverse events (TEAEs) was similar across the dupilumab and placebo groups (81% vs 83%). Viral upper respiratory tract infections, injection site reactions, upper respiratory tract infections, and bronchitis were the most common TEAEs reported.
Change from baseline in ACQ-5 “exceeded the minimal clinically important difference of 0.5 as early as week 2,” the investigators reported. “Dupilumab significantly improved asthma control, as measured by the ACQ-5, regardless of prior severe exacerbation history and was generally well tolerated.”
Disclosures: Several researchers received consulting fees from, were employed by, conducted contracted research, were advisory committee members, and/or were speakers/teachers for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Chiesi, Genentech, GlaxoSmithKline, Menarini, Novartis, Regeneron, Sanofi, Teva, and/or Uriach.
Visit Pulmonology Advisor‘s conference section for continuous coverage from ACAAI 2018
Corren J, Castro M, Maspero J, et al. Dupilumab improves asthma control in patients with uncontrolled, moderate-to-severe asthma, regardless of exacerbation history. Presented at: the Annual Scientific Meeting of the American College of Allergy, Asthma, and Immunology; November 15-19, 2018; Seattle, WA. Poster P216.