Jonas Daugherty1,2, Xiwu Lin3, Richard Baxter4, Robert Suruki5,6, Eric Bradford7. 1. a Department of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy , University of North Carolina , Chapel Hill , NC , USA. 2. b Value Outcomes and Epidemiology , PAREXEL International , Research Triangle Park , NC , USA. 3. c Value Evidence and Outcomes , GSK , Collegeville , PA , USA. 4. d GSK , Stevenage , UK. 5. e Worldwide Epidemiology , GSK , Research Triangle Park , NC , USA. 6. f Epidemiology UCB Biosciences , Research Triangle Park , NC , USA. 7. g Respiratory Therapeutic Area , GSK , Research Triangle Park , NC , USA.
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.
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.
Authors: Jonathan Steinfeld; Eric S Bradford; Judith Brown; Stephen Mallett; Steven W Yancey; Praveen Akuthota; Maria C Cid; Gerald J Gleich; David Jayne; Paneez Khoury; Carol A Langford; Peter A Merkel; Frank Moosig; Ulrich Specks; Peter F Weller; Michael E Wechsler Journal: J Allergy Clin Immunol Date: 2018-12-19 Impact factor: 10.793
Authors: David B Price; Frank Trudo; Jaco Voorham; Xiao Xu; Marjan Kerkhof; Joanna Ling Zhi Jie; Trung N Tran Journal: J Asthma Allergy Date: 2018-08-29