Asthma exacerbations were reduced with dupilumab in patients with type 2 (T2) inflammation, with and without evidence of allergic asthma, with no seasonal difference in reductions, according to post-hoc analysis findings published in the Annals of Allergy, Asthma & Immunology.
Although prior exacerbation history is a strong predictor of future exacerbations in asthma, exposure to allergens or viruses trigger asthma exacerbations seasonally. Dupilumab (a fully human monoclonal antibody) blocks the shared receptor interleukin (IL)-4 and IL-13 components, inhibiting their signaling. Therefore, investigators sought to assess the efficacy of dupilumab in reducing exacerbations across seasons in patients with T2 inflammatory asthma, including those with and without allergic asthma.
The investigators conducted a post-hoc analysis using data from the 52-week QUEST study (ClinicalTrials.gov Identifier: NCT02414854) and from the TRAVERSE study (ClinicalTrials.gov Identifier: NCT02134028), the open-label QUEST extension.
In QUEST, a phase 3, randomized, placebo-controlled trial, patients were randomly assigned to receive add-on subcutaneous therapy with 200 mg of dupilumab (loading dose, 400 mg), 300mg of dupilumab (loading dose, 600 mg), or matched placebo. Exacerbations were significantly reduced and pre-bronchodilator forced expiratory volume in 1 second (FEV1) improved in patients with uncontrolled, moderate-to-severe asthma with add-on dupilumab every 2 weeks vs placebo.
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Dupilumab reduced asthma exacerbations, with no difference in the reduction between seasons, in patients with type 2 inflammation, with and without evidence of allergic asthma.
In TRAVERSE, the long-term safety and efficacy of dupilumab was evaluated in patients with moderate-to-severe asthma, including patients from QUEST previously receiving placebo who subsequently initiated dupilumab therapy. All patients received dupilumab 300 mg every 2 weeks for 48 or 96 weeks.
For the post-hoc analysis, the investigators defined seasons as follows: in the Northern hemisphere, spring was March through May, summer was June through August, autumn was September through November, and winter was December through February; in the Southern hemisphere, spring was September through November, summer was December through February, autumn was March through May, and winter was June through August.
In QUEST, baseline demographics were similar between cohorts studied as were disease characteristics (51%-55% of patients on high-dose inhaled corticosteroids; 84%-85% experienced ongoing atopic medical conditions), and the mean severe exacerbation rates were 2.09 with dupilumab and 2.25 with placebo in the previous year. The majority of patients (74.2%) were in the Northern hemisphere, although patient characteristics were generally balanced between treatment arms for patients in the Northern and Southern hemispheres.
During QUEST, the investigators found the proportion of patients with type 2 inflammatory asthma receiving dupilumab vs placebo and experiencing at least 1 severe asthma exacerbation was 10.0% vs 20.8% in spring; 7.3% vs 18.2% summer; 12.6% vs 22.2% autumn; 12.0% vs 26.4% winter, respectively (P <.001 for placebo vs dupilumab in all seasons). In subgroups with and without evidence of allergic asthma and across seasons, reductions in the proportion of patients experiencing severe exacerbations were similar to the overall T2 population.
During TRAVERSE, the investigators noted that for up to 96 weeks and across both hemispheres, reductions in severe exacerbations observed during QUEST were sustained.
Post hoc study limitations include defining allergic asthma as including only perennial allergens; selection bias in the TRAVERSE study population; and the preponderance of patients from the Northern hemisphere.
“Dupilumab reduced asthma exacerbations, with no difference in the reduction between seasons, in patients with type 2 inflammation, with and without evidence of allergic asthma,” the investigators concluded. The study authors added, “The low rates of exacerbation observed with dupilumab treatment during QUEST were sustained during years 1 and 2 of TRAVERSE.”
Disclosure: This research was supported by Sanofi and Regeneron Pharmaceuticals Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
