New research was presented at ATS 2021, the American Thoracic Society International Conference, held May 15-18 in San Francisco. The features below highlight some of the studies focused on asthma that emerged from the conference.
High-Intensity Interval Training Reduces Daily Corticosteroid Need
For patients with asthma, high-intensity interval training was associated with a 24% reduction in daily inhaled corticosteroid use after 6 months without compromising asthma control. In a randomized controlled trial presented by Anders Pitzner-Fabricius, PhD-candidate, physically inactive adults with persistent asthma were randomized 2:1 to either a regimen of high-intensity interval training three times per week for 6 months or to usual lifestyle (control). Both groups were followed up without intervention for an additional 6 months. The change in mean inhaled corticosteroid use was reduced at 6 months in the high-intensity interval training arm by -234 micrograms (95% CI, -391 to -77), and even further at 12 months, even without intervention for the second 6-month period (-314 micrograms; 95% CI, -477 to -151). Additionally, 71.4% of those with high adherence reduced their inhaled corticosteroid use by at least 25%, compared with 48.8% of the control group, when stratified by adherence to high-intensity interval training. In adults with asthma, high-intensity interval exercise training has the potential to improve asthma control, reduce inhaled corticosteroid use, and has potential long-term positive lifestyle impacts, Pitzer-Fabricius noted.
Nearly Three-Fold Greater Response to Tezepelumab than Placebo
Patients with severe, uncontrolled asthma showed overall 2.8-fold higher odds of improved clinical responses to tezepelumab than placebo, including exacerbation reduction, improved lung function, better asthma control, and clinician assessment. An on-treatment analysis of responses to tezepelumab using data from the completed phase III, double-blind, placebo-controlled NAVIGATOR trial was presented by Njira Lucia Lugogo, MD. Participants aged 12-80 were randomized to subcutaneous injections of 210 mg tezepelumab or placebo every 4 weeks for 52 weeks. Participants continued their medium- or high-dose corticosteroid inhalers and at least one additional asthma-control medication. At 52 weeks, the primary endpoint of annual asthma exacerbation rate was met. The proportion of responders was higher in the tezepelumab group than in the placebo group for exacerbation reduction (85.4% vs 67.5%; OR, 2.82); Asthma Control Questionnaire (ACQ)-6 total score (86.9% vs 76.6%; OR, 2.05); improvement from baseline pre-bronchodilator FEV1 (60.3% vs 49.9%; OR, 1.52); and Clinical Global Impression of Change score (81.5% vs 67.7%; OR, 2.21). In the tezepelumab group, the proportion of complete responders was also greater (48.2% vs 25.3%; OR, 2.78). “Overall, these results add an important patient-level perspective to the primary study results,” Dr. Lugogo concluded. Across each measure, tezepelumab recipients were more likely to have a response; the greatest difference observed was for exacerbation reduction. In addition, 48% of patients receiving tezepelumab had a complete response and achieved significant and clinically relevant improvements in all four response measures.
Dupilumab Efficacious for Type 2 Asthma, Despite Atopic Comorbidities
Dupilumab reduced severe asthma exacerbation rates and improved overall lung function in children with moderate to severe asthma, independent of the presence of atopic comorbidities—including chronic rhinosinusitis, nasal polyps, or eosinophilic esophagitis—according to results from a post hoc analysis of the phase III Evaluation of Dupilumab in Children with Uncontrolled Asthma (Liberty Asthma VOYAGE) trial. Theresa W. Guilbert, MD, MS, presented the results of the analysis, which examined the effect of dupilumab on type 2 inflammation and comorbid atopic disorders. Dupilumab reduced severe exacerbation rates and by the end of treatment had improved the percent predicted pre-bronchodilator FEV1 in children aged 6-11 with uncontrolled, moderate to severe asthma, in patients with or without atopic comorbidities. The main Liberty Asthma VOYAGE trail evaluated the effectiveness of dupilumab 100/200 mg every 2 weeks compared with placebo in children aged 6-11 with uncontrolled persistent asthma. Positive effects were noted on severe asthma exacerbations. In the current post hoc analysis, 408 participants were ranked by their burden of comorbid disease into groups without any comorbid disease, with one comorbid phenotype, or with more than one ongoing comorbid disease, and evaluated during a 52-week treatment period. Comorbid diseases self-reported at baseline included atopic dermatitis, allergic rhinitis, allergic conjunctivitis, food allergy, hives, chronic rhinosinusitis, nasal polyposis, and eosinophilic esophagitis. Participants were evaluated via the annualized rate of severe asthma exacerbations and lung function, measured by change from baseline in percent predicted prebronchodilator FEV1 (FEV1pp). Compared with patients treated with placebo, those treated with dupilumab experienced reduced severe asthma exacerbations despite the presence or lack of comorbid disease. Lung function improved most in patients with more than one atopic comorbidity treated with dupilumab at 12 weeks; pre-bronchodilator FEV1pp after 12 weeks was greatly improved by dupilumab treatment. Among patients with no atopic comorbidities, there was no difference in changes from baseline in pre-bronchodilator FEV1pp.
Albuterol-Budesonide Beats Albuterol Alone for Asthma Exacerbation
In patients with uncontrolled moderate to severe asthma, the risk for asthmatic exacerbation was reduced considerably with use of a fixed-dose inhaler with a combination of albuterol and budesonide as needed, compared with the use of an inhaler with albuterol alone as needed, in a dose-dependent manner, according to results of the phase III, double-blind, randomized, event-driven MANDALA trial. Presented by Alberto Papi, MD, MANDALA enrolled patients with moderate to severe asthma who had severe exacerbation in the prior 12 months. Participants were assigned to combination with a high dose of budesonide (albuterol 180 µg/budesonide 160 µg), a lower-dose arm (albuterol 180 µg/budesonide 800 µg), or albuterol 180 µg alone through blinded, pressurized, metered-dose inhalers. All patients continued maintenance inhaled corticosteroids for their asthma, either with or without other medications. The primary endpoint—time to first severe asthma exacerbation—was reduced 27% among patients assigned to the higher fixed-dose combination compared with albuterol 180 µg alone (HR, 0.73; 95% CI, 0.61-0.88). Similarly, a 17% reduction was seen with the lower-dose combination arm (HR, 0.83; 95% CI, 0.7-0.99), but the data did suggest a dose response. In an additional intention-to-treat analysis, risk was reduced by 26% with the higher-dose combination (HR 0.74; 95% CI, 0.62–0.89) and 16% with the lower-dose combination (HR 0.84; 95% CI, 0.71-1.0). Incidence rates for any adverse event were nearly 46.2% in the higher-dose combination group, 47.1% in the lower-dose combination group, and 46.4% in the albuterol-only group. Serious adverse events were observed in 5.2%, 3.8%, and 4.5%, respectively. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection. “Given the efficacy of adding budesonide to albuterol as a rescue medication and the duration of the treatment, we believe that this is going to be a potential change in the paradigm of the use of rescue medication,” Dr. Papi concluded.
