OBJECTIVES : Despite the availability of medium-to-high-dose inhaled corticosteroid-and-long-acting beta agonist (ICS-LABA) combination therapies, some adult patients with asthma remain uncontrolled and still experience symptoms. To gain an understanding of the clinical burden for this patient group, we conducted a systematic literature review to identify and summarize the current observational literature.

METHODS : Systematic searches were conducted in MEDLINE, Embase, and the National Health Service’s Economic Evaluation Databases to identify observational studies published in English from 1/1/2009-3/20/2019. Methods followed PRISMA guidelines. Studies conducted in asthma patients aged 18+ years using ICS-LABA at GINA steps 4 or 5, that reported clinical endpoints, including lung function, asthma control, and exacerbations were eligible for inclusion.

RESULTS : The systematic review identified 67 studies reporting on aspects of the clinical burden in patients with asthma at GINA step 4 or 5 that met the criteria for inclusion. Baseline lung function reported across studies indicated reduced respiratory function; mean forced expiratory volume in one second (FEV₁) volume ranged from 1.69L to 2.89L, while FEV₁% predicted (pre-bronchodilation) ranged from 60% to 80%, indicating mild obstruction. Mean baseline ACT scores ranged from 9.7 to 14.3, while ACQ scores, indicated lack of control for each tool variation (ACQ-7: 2.0 to 3.4; ACQ-5: 0.99 to 3.8; ACQ-6: 1.9 to 2.6). Underscoring the lack of disease control, between 14.5% and 97.0% of patients experienced ≥1 moderate to severe exacerbation in the prior year across the included studies. Despite the range in results, most studies used similar criteria for defining exacerbation events. The mean annual rate of any exacerbation per patient ranged widely from 0.4 to 6.0, while the mean annual rate of severe exacerbations ranged from 1.6 to 3.6 per patient.

CONCLUSIONS : Study results suggest that these patients have diminished lung function, poor disease control, and a proportion of this population experience exacerbations. Funding: GSK (HO-18-17246)