The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis

ABSTRACT

Objective: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. Methods: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6–12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004–2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. Results: Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0–≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0–2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. Conclusions: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.

KEYWORDS:

• Adverse event
• claims database
• diabetes
• myocardial infarction
• oral glucocorticoids
• osteoporosis cataracts
• pharmacology
• peptic ulcer
• stroke

Acknowledgements

The authors wish to thank Alex Lowe, PhD, from Fishawack Indicia Ltd, UK who provided editorial support with developing this manuscript (in the form of writing assistance, including development of the initial outline and draft based on author input, assembling tables and figures, collating authors comments, grammatical editing and referencing), funded by GSK.

Declaration of interest

JD was an employee of GSK during the conduct of the study and is currently a doctoral student at UNC Eshelman School of Pharmacy, University of North Carolina; XL was an employee of GSK during the conduct of the study and holds stock/shares in GSK; RB was a contingency worker, on assignment at GSK at the time of the study and is currently a contingency worker at UCB Biosciences and Lundbeck, Denmark; RS is a former employee of GSK, holds stock/shares in GSK and is a current employee of UCB Biosciences. EB is an employee of GSK and holds stock/shares in GSK.

Authors were in full editorial control of publication target journal, content and conclusions and accepted full responsibility for final approval of a manuscript describing this GSK-sponsored research. As agreed by authors before the preparation of the manuscript began, authors were provided with open and transparent access to data supporting publications including access to data tables, final study reports, case report forms and raw data as needed. The sponsor did not place any restrictions on access to the data or on the statements made in the manuscript.

Author contributions

JD, XL, RB, and RS, contributed to the study concept and design, data acquisition and analysis and interpretation. EB contributed to the study concept and design, and analysis and interpretation. All authors were involved in the preparation and review of the manuscript and approved the final version to be submitted.

Funding

The study was funded by GSK (HO-13-13614). This study was approved by CPRD's Independent Scientific Advisory Committee (ISAC), approval number 14_137R.