Updates on the Treatment of Asthma

Asthma affects more than 25 million individuals in the United States, and remains a significant source of morbidity, mortality, and healthcare-related costs. Although many patients with asthma can achieve disease control with standard therapies, others have severe asthma that remains inadequately controlled despite adherence to conventional treatments, resulting in ongoing disease burden, poor quality of life, and a decline in lung function. Researchers continue to study the safety and efficacy of novel agents for the treatment of asthma, as well as patient- and disease-related factors that can affect clinical outcomes.

This article provides an overview of results from key studies on asthma that were scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology’s annual meeting, which was canceled because of the COVID-19 crisis.

Baseline FeNO Identifies Patients with Asthma at Risk for Exacerbation

Type 2 inflammation driven by inflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13 plays a critical role in approximately 50% of patients with moderate-to-severe asthma. Biomarkers such as fractional exhaled nitric oxide (FeNO) are associated with type 2 inflammation, and can be useful for inflammatory phenotyping and helpful for guiding treatment decisions.

The phase 3 Liberty Asthma QUEST trial randomized 1902 patients with uncontrolled asthma in a 2:2:1:1 ratio to add-on subcutaneous dupilumab (Dupixent) at a dose of 200 or 300 mg every 2 weeks or matched-volume placebo for 52 weeks. In an ad-hoc analysis, William Busse, MD, and colleagues assessed the prognostic value of baseline FeNO levels of 620 patients who were randomized to the placebo arm of the study.1

Patients enrolled in the Liberty Asthma QUEST trial had moderate-to-severe asthma, which was uncontrolled with inhaled glucocorticoids plus ≤2 controller medications and a history of ≥1 exacerbations in the past year. In addition, participants had a prebronchodilator forced expiratory volume in 1 second (FEV1) ≤80% of the predicted normal value and a score on the 5-item Asthma Control Questionnaire of ≥1.5. There was no minimum requirement for baseline type 2 biomarkers. The annualized rate of severe asthma exacerbation during the 52-week treatment period was assessed in relation to baseline FeNO levels and further cross-classified by baseline blood eosinophil counts (<150, 150 to <300, and ≥300 cells/μL).

After adjusting for baseline blood eosinophil counts and other clinical characteristics, the researchers found that patients with baseline FeNO levels ≥50 parts per billion (ppb) had an exacerbation rate 1.54 times that of patients with baseline FeNO levels <25 ppb (95% confidence interval [CI], 1.11-2.14). After controlling for potential differences in other clinical characteristics, patients with baseline FeNO levels ≥50 ppb and blood eosinophil counts ≥300 cells/μL were found to have an exacerbation rate 3.19 times that of patients with baseline FeNO levels <25 ppb and blood eosinophil counts <150 cells/μL (95% CI, 1.62-6.28).

In patients with uncontrolled, moderate-to-severe asthma, higher baseline FeNO levels were associated with higher rates of severe asthma exacerbation over the 52-week study period, independent of standard clinical characteristics. For patients with high baseline FeNO levels and blood eosinophil counts of ≥300 cells/μL, the risk for exacerbation was particularly high.

“These results suggest that FeNO, independently and in combination with blood eosinophils, identifies patients at increased risk of subsequent exacerbations,” Dr Busse and colleagues concluded.

Baseline Clinical Characteristics Associated with Enhanced Benralizumab EFFICACYin Asthma

Benralizumab (Fasenra) is an anti-­eosinophilic monoclonal antibody that has been shown to improve disease control in patients with severe, uncontrolled asthma and eosinophilia. Certain clinical characteristics significantly associated with enhanced response to benralizumab in patients with severe, uncontrolled asthma and high blood eosinophil counts (≥300 cells/μL) have previously been reported. In a post-hoc analysis, Bradley Chipps, MD, and colleagues evaluated the effect of these baseline factors on clinical response to benralizumab in patients with moderate blood eosinophil counts (150-299 cells/μL).2

The researchers analyzed pooled data from the phase 3 SIROCCO and CALIMA clinical trials, 2 similar randomized placebo-controlled studies that evaluated the safety and efficacy of benralizumab in patients with severe, uncontrolled asthma and eosinophilia. They evaluated baseline factors including oral corticosteroid use, history of nasal polyposis, prebronchodilator forced vital capacity <65% predicted, history of ≥3 exacerbations during the year before enrollment, and age of asthma diagnosis of ≥18 years. The pooled data of patients receiving benralizumab every 4 weeks, every 8 weeks, and those receiving placebo were compared.

Among 278 enrolled patients with severe, uncontrolled asthma and baseline blood eosinophilia counts of 150 to 299 cells/μL, a number of baseline factors, including ≥3 previous exacerbations, oral corticosteroid use, and history of nasal polyposis, were associated with enhanced exacerbation rate reduction (rate ratio [95% CI])—0.57 (0.34, 0.97), 0.49 (0.24, 1.04), and 0.34 (0.11, 1.02), respectively—compared with the total subpopulation—0.59 (0.40, 0.88). Baseline patient characteristics of ≥3 previous exacerbations, oral corticosteroid use, prebronchodilator forced vital capacity <65% predicted, and asthma diagnosis at age ≥18 years were associated with enhanced improvement in prebronchodilator FEV1 (difference vs placebo [95% CI])—0.116 (–0.016, 0.249), 0.130 (–0.078, 0.337), 0.214 (0.048, 0.380), and 0.142 (0.048, 0.235), respectively—compared with the total subpopulation—0.101 (0.016, 0.186).

Dr Chipps and colleagues concluded that identification of certain baseline clinical characteristics of patients with severe, uncontrolled asthma and moderate eosinophilia may help to predict responsiveness to treatment with benralizumab and lead to fewer exacerbations and greater lung function improvements in this patient population.

Effect of Tezepelumab on Asthma Exacerbations According to BMI

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine that plays a critical role in airway inflammation and asthma pathogenesis. The phase 2b PATHWAY clinical trial demonstrated that tezepelumab reduced asthma exacerbation rates compared with placebo in adults with severe, uncontrolled asthma, irrespective of baseline characteristics. In a post-hoc analysis of data from the PATHWAY study, Chris Ambrose, MD, MBA, and colleagues sought to evaluate the efficacy of tezepelumab in decreasing asthma exacerbations according to baseline body mass index (BMI).3

A total of 550 patients aged 18 to 75 years with severe, uncontrolled asthma were randomized to receive subcutaneous tezepelumab 70 mg every 4 weeks (low dose), 210 mg every 4 weeks (medium dose), 280 mg every 2 weeks (high dose), or placebo, for 52 weeks. Patients were evaluated by baseline BMI subgroups of <25 kg/m2, 25 to <30 kg/m2, and ≥30 kg/m2. The annualized asthma exacerbation rate (AAER) was estimated in each subgroup based on baseline BMI.

For patients receiving placebo, the AAERs over the 52-week study period were similar in all BMI subgroups, with 0.70 to 0.76 exacerbations per person-year. Patients receiving tezepelumab experienced a reduction in exacerbation rate across all BMI subgroups. The AAER for pooled tezepelumab groups was reduced by 79% in patients with BMI <25 kg/m2, 70% in patients with BMI 25 to <30 kg/m2, and 50% in patients with BMI ≥30 kg/m2, compared with placebo. Patients in the medium-dose tezepelumab treatment group were found to have a reduction in exacerbations across all BMI subgroups, compared with patients receiving placebo. In the medium-dose treatment group, AAER was reduced by 83% in patients with BMI <25 kg/m2, 62% in patients with BMI 25 to <30 kg/m2, and 68% in patients with BMI ≥30 kg/m2, compared with placebo.

The analysis demonstrated that tezepelumab reduced the rate of asthma exacerbations in patients with severe, uncontrolled asthma in all baseline BMI subgroups. Dr Ambrose and colleagues concluded that these results build on findings of previous studies demonstrating the effectiveness of tezepelumab in patients with asthma, independent of baseline clinical characteristics.

“The results of this study provide further evidence that tezepelumab can meaningfully reduce exacerbations in a broad population of patients with severe asthma,” the researchers concluded.

Systemic Corticosteroid Use Can Double Lifetime Healthcare Costs for Adults with Asthma

The use of systemic corticosteroids (SCS) is associated with increased risk for acute and chronic complications. These adverse events can result in higher healthcare costs for patients with asthma. In this study, researchers sought to estimate the effect of SCS use on lifetime healthcare costs for patients in the United States with persistent asthma.4

Nicole M. Zimmerman, MS, and colleagues identified adult patients with asthma in the IBM MarketScan databases between January 2003 and July 2016. Patients met the Healthcare Effectiveness Data and Information Set (HEDIS) criteria for persistent asthma. Eligible patients were enrolled for 1 year before and 3 years after their first prescription for SCS. A control group of patients with asthma who were not treated with SCS were enrolled for 1 year before and 3 years after the date of their asthma diagnosis. Patients treated with SCS were segmented based on SCS use into low-frequency (1-3 claims for SCS) and high-frequency (≥4 claims for SCS) groups. To evaluate the incurred healthcare costs, 5-, 10-, 15-, 20-, and 25-year covariate-adjusted cumulative total healthcare costs were extrapolated for all patients from a mixed model, with a random intercept including covariates for the steroid group at year 1, steroid group-by-year interaction, and for other patient characteristics.

Patients in the high-frequency SCS group (N = 5112) experienced the greatest change in healthcare cost, followed by patients in the low-frequency SCS group (N = 40,315). The non-SCS control group incurred the lowest costs over time (N = 34,570). The estimated lifetime per-patient mean healthcare costs by year 25 were approximately $2.2 million for high-frequency SCS users, $1.9 million for low-frequency SCS users, and $1.1 million for non-SCS patient controls.

The use of SCS in the treatment of patients with persistent asthma was associated with up to double the healthcare expenditure over the course of a patient’s lifetime. The researchers concluded that, “strategies to reduce the use of SCS, when appropriate, may be an effective means of minimizing patients’ healthcare cost burden.”

Severe Asthma Associated with High Burden of Exacerbation and Antibiotic Use

Patients with severe asthma are at increased risk for exacerbations related to their condition. However, provider-verified characteristics of exacerbations in patients in the United States with severe asthma have not previously been described. In this study, researchers identify the characteristics of exacerbations in severe asthma in a national sample of patients treated by asthma specialists.

The CHRONICLE trial is an ongoing, multicenter, observational study of adult patients with severe asthma treated by allergists/immunologists or pulmonologists in the United States. Patients enrolled in the trial are receiving biologic therapy, and have not achieved control on high-dose (HD ICS+) inhaled corticosteroids with additional controllers or are receiving maintenance SCS. Healthcare providers of patients with severe asthma are required to report characteristics of all documented exacerbations occurring in the 12 months before enrollment. Warner Carr, MD, and colleagues reported on the results for patients enrolled between February 2018 and February 2019.5

Among 796 patients enrolled across 89 sites, 46% of patients had experienced exacerbations in the previous 12 months, with 18% of patients reporting 1 exacerbation, 13% reporting 2 exacerbations, and 15% reporting ≥3 exacerbations. A total of 875 exacerbations were reported, with a mean duration of 13 days. Primary suspected triggers were reported in 35% of exacerbations, and the most frequently reported triggers were allergen (8%), bacterial (7%), unknown respiratory infection (6%), and viral infection (4%).

Of the 875 reported exacerbations, 89% required treatment with SCS, 93% resulted in administration of oral medication, 16% were treated with injections, and 45% were treated with antibiotics. A healthcare provider visit was required in 37% of exacerbations, an emergency department visit was required in 17%, and hospitalization was required in 12%. A total of 109 asthma hospitalizations occurred in 70 patients, with a mean duration of 5.4 days. Of the asthma hospitalizations, 15% required care in an intensive care unit, and 1% required intubation.

The researchers concluded that exacerbations were found to be common among patients with severe asthma treated by US allergists/immunologists and pulmonologists and were associated with high burden. Most provider-documented exacerbations required SCS therapy. Less severe exacerbations were infrequently reported by patients. Of note, nearly half of reported exacerbations were treated with antibiotics, leading to a possible opportunity to optimize the antibiotic stewardship.

Reduced HRQoL and Productivity in Patients with Severe Asthma

Patients with severe asthma experience significantly reduced health-related quality of life (HRQoL) and productivity. However, there are no contemporary estimates of HRQoL and productivity from a national, real-world sample of adults in the United States with severe asthma. Weily Soong, MD, and colleagues reported results of surveys assessing HRQoL and productivity among patients with severe asthma enrolled in the ongoing CHRONICLE observational trial.6

Patients enrolled in the study completed surveys measuring quality of life and impairments in work and activities. The St. George’s Respiratory Questionnaire (SGRQ) references the previous 3 months, evaluating impairment on a scale of 0 to 100, with a score of 100 representing maximum impairment. The Work Productivity and Activity Impairment-Asthma survey (WPAI) references the previous 7 days and is reported as the percentage of impairment. Responses to these surveys were summarized by treatment category for patients enrolled in the trial February 2018 to from February 2019.

Among 796 patients enrolled across 89 sites, 481 (60%) completed both surveys. The demographics and other characteristics of patients who completed the surveys and those who did not were generally similar. A total of 370 patients were receiving biologic therapy, 91 patients were receiving on (HD ICS+ and 64 patients were receiving maintenance systemic corticosteroids (mSCS). The mean total SGRQ score was 39 for patients receiving biologic therapy, 45 for patients on HD ICS+, and 58 for patients receiving mSCS. Good or very good overall health was reported by 54% of patients on biologic therapy, 55% of patients on HD ICS+, and 19% of patients on mSCS. Mean activity impairment reported on the WPAI survey was 31% for patients on biologic therapy, 38% for patients on HD ICS+, and 55% for patients on mSCS. Among patients who were employed, the reported mean overall work impairment in each treatment group was 19%, 26%, and 38%, respectively.

According to Dr Soong and colleagues, patients in the United States with severe asthma reported a reduction in HRQoL and work- and activity-related productivity. Impairment was highest among patients receiving mSCS and lowest among those receiving biologic therapy. The researchers noted that “rates of patient-reported good health were similar among biologic and HD ICS+ patients despite HRQoL and productivity differences, suggesting patient-reported health may mask meaningful impairment.”

Asthma Is More Prevalent and More Severe in Women

Although asthma is known to be more prevalent in women than men, less is known about how disease severity in women compares with that in men. Olga Ryan, DrPH, MPH, MBA, and colleagues performed a post-hoc analysis to evaluate gender differences in asthma exacerbation severity.7

The researchers performed the analysis of pooled data from the phase 3 SIROCCO and CALIMA trials, which evaluated the safety and efficacy of benralizumab in patients with severe, uncontrolled asthma and eosinophilia. Enrolled participants were already receiving HD ICS and long-acting beta agonist therapy.

Participants received benralizumab 30 mg subcutaneously every 4 weeks, every 8 weeks, or placebo. Researchers evaluated mean immunoglobulin E (IgE) concentrations, blood eosinophil counts, history of atopy, and baseline exacerbation rates in men and women.

In this analysis of 996 women and 568 men with severe asthma, women were found to have lower mean IgE concentrations compared with men (514 vs 771 IU/mL). Baseline blood eosinophil counts were similar between women and men (470 and 480 cells/μL, respectively). Fewer women than men had atopic asthma (57.9% vs 66.9%). Asthma reversibility was 26.4% for women and 25.0% for men.

Women and men reported similar baseline exacerbation rates, with 2.9 for women and 2.8 for men. However, a greater percentage of women than men were found to have ≥3 exacerbations in the year before study enrollment (41.5% vs 36.1%). More women than men experienced asthma exacerbations leading to emergency department visits; 8.4% versus 7.0% for 1 exacerbation, and 6.1% versus 1.9% for 2 exacerbations. Similarly, a greater percentage of women than men had exacerbations leading to hospitalization; 14.9% versus 10.9% for 1 exacerbation, and 7.5% versus 6.2% for 2 exacerbations. In addition, more women than men required mechanical ventilation (4.0% vs 2.8%). Differences in comorbidities were also observed. Women and men were found to experience similar reductions in exacerbations with benralizumab treatment.

According to Dr Ryan and colleagues, the analysis of pooled data from the SIROCCO and CALIMA studies revealed that women and men with severe asthma and eosinophilia had similar baseline blood eosinophil counts and experienced similar clinical benefit from treatment with benralizumab. However, they noted, “women had more severe disease, were less likely to have atopic asthma, and had lesser IgE concentrations.”


  1. Busse W, Pavord I, Wenzel S, et al. Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled moderate-to-severe asthma receiving placebo in the Liberty Asthma Quest study. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 063.
  2. Chipps B, Corren J, Israel E, et al. Influence of key clinical baseline characteristics on benralizumab response for patients with severe, uncontrolled asthma and moderate blood eosinophilia. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 068.
  3. Ambrose C, Colice G, Salapa K, et al. Effect of tezepelumab on exacerbations in patients with severe uncontrolled asthma, according to baseline body mass index: results from the phase 2b Pathway study. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 075.
  4. Zimmerman N, Chung Y, Kreindler J, et al. Lifetime health care costs associated with systemic corticosteroid use in adults with persistent asthma. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 231.
  5. Carr W, Lugogo N, Moore W, et al. High burden of exacerbations of severe asthma: results from a real-world study of patients treated by subspecialist in the United States. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 339.
  6. Soong W, Chipps B, Trevor J, et al. Health-related quality of life and productivity among a real-world cohort of severe asthma patients in the United States. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 654.
  7. Ryan O, Katial R, Hirsch I, et al. Asthma exacerbation severity is greater for women than for men. J Allergy Clin Immunol. 2020;145(Issue 2; Suppl). Abstract 664.

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