Spotlighting Emerging Insights in the Management of Asthma

With updates on the management of asthma presented last year addressing treatment recommendations, including for use of mepolizumab, dupilumab, and long-acting- (LABAs) and short-acting-beta-agonists (SABAs), findings of abstracts presented at this year’s CHEST Annual Meeting 2021 evaluated the efficacy and safety of these therapeutic options.

How ICS/LABA/LAMA Affects Treatment Outcomes in Inadequately Controlled Asthma

Kicking off the session, “Asthma Management: New Insights,” panelist Nicola Hanania, MD, MS, FCCP, director, Airways Clinical Research Center, Baylor College of Medicine, presented findings of a study which investigated single-inhaler fluticasone furoate (FF) plus umeclidinium (UMEC) plus vilanterol (VI) vs FF/VI alone in patients with inadequately controlled asthma.

As 30% to 50% of patients with moderate to severe asthma remain inadequately controlled with inhaled corticosteroid (ICS) plus LABA, the addition of UMEC, a long-acting muscarinic antagonist (LAMA), was examined in the CAPTAIN phase 3A, randomized, 24-52 week, parallel-group study.

Assessing the primary outcome of improvement from baseline to week 24 in trough forced expiratory volume in 1 second (FEV₁), findings showed significant improvement in trough FEV₁ following the addition of UMEC to FF/VI or when increasing the FF dose. 

Moreover, the magnitude of improvement in trough FEV₁ was indicated to be greater for those treated with FF/UMEC/VI compared with increasing the dose of FF, but those treated with the higher FF dose reported numerical reductions in the annualized rate of moderate/severe asthma exacerbations—a trend that was only found in older patients treated with FF/UMEC/VI. All findings were independent of age. 

“A take home message is that patients with asthma who are inadequately controlled, when UMEC is integrated with ICS/LABA, there seems to be improvement in lung function no matter what age group you’re dealing with,” said Hanania, who is also the editor-in-chief of Respiratory Medicine.

How SABAs Impact Asthma Exacerbations, Adverse Health Outcomes in Patients

Although SABAs served as the first-line treatment of asthma for 50 years, the Global Initiative for Asthma (GINA) no longer recommends SABA-only treatment as step 1 amid associations with poor control and treatment outcomes.

Notably, SABA use without concomitant ICS has been found to increase the risk of asthma exacerbations requiring systemic corticosteroids (SCS), in which 2 or more SCS bursts per year can lead to the development of acute and chronic illnesses.

With all adults and adolescents now recommended to receive ICS treatments to reduce the risk of serious exacerbations, panelist Njira Lugogo, MD, clinical associate professor, Pulmonary Diseases, University of Michigan Health, presented next on study findings that sought to quantify the impact of SABA-only use on annual SCS exposures and adverse health outcomes in patients with asthma.

Assessing data of US patients aged 12 years and older derived from IBM MarketScan research databases (2010-2017), SABA claims between 2011 and 2016 were observed and categorized according to the number of fills:

• Low (well-controlled), 1 SABA fill with 1 or more controller fills per year (n = 290,467)
• Medium (not well-controlled), 2 to 3 SABA fills with or without any controller fills per year (n = 261,117)
• High (very poorly controlled), 4 or more SABA fills with or without any controller fills per year (n = 176,348)
  

As claims grew, findings showed notable increases in SCS exposures, with 34.4% of patients with high SABA fills exposed to 500 mg SCS vs 18.6% of patients with low SABA fills. Those with high annual SABA fills were also found to present with SCS exposure of 1000 mg at rates higher than that found overall (13.9% vs 8.8%).

“With increasing SABA claims from low to medium to high, the proportion of patients with adverse health conditions increased,” added Lugogo. These conditions included hypertension, anxiety/depression, obesity, and type 2 diabetes. “This rescue paradigm may serve to reduce SCS load and, thereby, mitigate development of adverse health conditions associated with steroid exposures.”

Assessing Biologics in Treatment of Asthma

Shifting to a different study, Lugogo presented findings of a retrospective analysis investigating the use of mepolizumab, an FDA-approved anti–interleukin (IL)-5 treatment in asthma, on exacerbations, oral corticosteroid (OCS) use, and cost in high-cost patients with severe asthma after 12 months.

In a prior study, mepolizumab was associated with a 50% reduction in oral steroid doses, but while some patients had a complete reduction in oral steroid dose, others reported no reduction at all.

Noting that patients with severe asthma use a majority of health care resources and account for most of the spending, Lugogo said that improving the health outcomes of this group could have a disproportionately large effect on decreasing costs within the health care system.

Including 281 patients with asthma characterized by high-cost (total health care expenditures ≥ 80th percentile; n = 148), severe disease (n = 75), or both (n = 58), participants were assessed for the primary outcomes of change in the mean rate of asthma exacerbations, change in OCS use, and change in asthma exacerbation-related health care costs after 12 months of mepolizumab use.

Compared with baseline, mepolizumab use was associated with significant reductions of 40% in the mean rate of any exacerbation among participants (P < .001), 50% in the mean rate of exacerbations resulting in hospitalization (P < .001), 29% in the mean number of OCS pharmacy claims 12-months before and after use (P < .001), and 35% in the mean number of OCS bursts 12-months before and after use (P < .01).

Notably, 61.3% of patients reduced their OCS dose by at least half in the follow-up period.

“These results suggest that patients with severe asthma, who use the majority of resources and account for most of the health care system spending, as defined by high cost, demonstrated clinically significant benefit from mepolizumab in a real-world setting,” concluded Lugogo.

Following the positive cost- and efficacy-related impact shown with mepolizumab, findings investigating another FDA-approved biologic, dupilumab, examined the long-term effect of the indication on lung function of patients with type 2 asthma and those dependent on OCS.

In findings of the LIBERTY ASTHMA TRAVERSE study, dupilumab, an anti IL-5 and IL-13 biologic, was associated with significantly improved pre-bronchodilator forced vital capacity (FVC), forced expiratory flow at 25 and 75% (FEF_25-75%), and FEV₁ from the QUEST baseline to up to 3 years.

Findings of the VENTURE study that focused on OCS-dependent patients of the LIBERTY ASTHMA TRAVERSE study cohort additionally showed significant improvement in pre-bronchodilator FEV₁, FVC, and FEF_25-75% from parent study baseline through 96 weeks.