Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment

Objective: This study sought to characterize the epidemiologic, clinical, humanistic, and economic burden of patients with asthma uncontrolled by GINA Steps 4 or 5 treatment (severe, uncontrolled asthma [SUA]). Methods: A systematic literature review adhering to PRISMA guidelines was performed. Relevant publications were searched for in MEDLINE and EMBASE from January 2004 to September 2016 and in a conference proceedings database from January 2012 to October 2016. Studies were screened using the Population, Intervention, Comparator, Outcomes, Study Design, and Time (PICOS-T) framework. Studies of SUA with observational (prospective and retrospective), randomized, or nonrandomized study designs; adult patient populations; sample sizes >= 20 patients; epidemiologic or clinical outcomes, patient-reported outcomes (PROs), or economic outcomes were included. For our analysis, SUA was defined as inadequate control of asthma, despite the use of medium- to high-dosage inhaled corticosteroids and at least one additional treatment. Results: A total of 195 articles reporting unique study populations were included. Prevalence of SUA was as great as 87.4% for patients with severe asthma, although values varied depending on the criteria used to define asthma control. Compared with patients with severe asthma who were controlled, patients with SUA experienced more symptoms, night-time awakenings, rescue medication use, and worse PROs. SUA-associated costs were 3-times greater than costs for patients with severe, controlled disease. Conclusion: Despite the availability of approved asthma treatments, this literature analysis confirms that SUA poses a substantial epidemiologic, clinical, humanistic, and economic burden. Published data are limited for certain aspects of SUA, highlighting a need for further research.