title: Dose-Response Relationship Between Long-Term Systemic Corticosteroid Use and Related Complications in Patients with Severe Asthma.
abstract: BACKGROUND
  Systemic corticosteroids are a leading cause of drug-related complications, yet little has been done to quantify the dose-response relationship between systemic corticosteroid exposure and complications in patients with severe asthma.
  
  
  OBJECTIVE
  To (a) evaluate the risk of developing systemic corticosteroid-related complications by corticosteroid exposure in severe asthma and (b) quantify the associated health care resource utilization and costs.
  
  
  METHODS
  This is a retrospective study using administrative claims data from a large commercial database between 2003 and 2014. Multivariate generalized estimating equation models were used to compare corticosteroid-related complications in patients continuously exposed to at least 5 mg of prednisone or equivalent for ≥ 6 months with a 1:1 ratio of propensity score-matched patients with asthma who did not use corticosteroids.
  
  
  RESULTS
  A total of 12,697 corticosteroid users and as many matched nonusers were identified. The odds of developing associated complications increased significantly in a dose-dependent manner with systemic corticosteroid exposure: odds ratios were 2.50, 2.95, and 3.32 (P values <0.05) for low (defined as < 5 mg/day), medium (≥ 5-10 mg/day), and high (>10 mg/day) exposure, respectively, relative to no exposure. Health care resource utilization increased significantly with levels of systemic corticosteroid exposure. Hence, incidence rate ratios for inpatient visits with low, medium, and high exposure relative to none were estimated to be 1.86, 2.40, and 3.37, respectively (P < 0.05).
  
  
  CONCLUSIONS
  A significant dose-response relationship was found between the long-term use of systemic corticosteroids and the risk of developing systemic corticosteroid-related complications in patients with severe asthma, resulting in increased burden and costs on the health care system that intensified with systemic corticosteroid exposure.
  
  
  BACKGROUND
  Funding for this study was provided by GlaxoSmithKline, Study number H0-15-15930, to Analysis Group for the conduct of this study. Lefebvre, Duh, and Gozalo are employees of Analysis Group, a contract research organization that has received research grants from GlaxoSmithKline. Robitaille was employed by Analysis Group at the time of this study. Yancey, Forshag, Lin, and Albers are employees of GlaxoSmithKline and own company stock. Dalal and Ortega were employed by GlaxoSmithKline at the time of this study. Lefebvre had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Additionally, all listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Study concept and design were contributed by Dalal, Duh, Albers, Yancey, Ortega, Forshag, and Lefebvre. Data acquisition was by Dalal, Gozalo, Robitaille, Forshag, and Lefebvre and was analyzed and interpreted by Dalal, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, and Lefebvre. The manuscript was drafted and approved by Dalal, Duh, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, Lin, and Lefebvre.
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Anand A
authors.initials: AA
authors.lastname: Dalal
authors.affiliation: 2 Analysis Group, Boston, Massachusetts.
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
authors.affiliation: 3 Groupe d'analyse, Ltée, Montréal, Québec, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gozalo
authors.affiliation: 3 Groupe d'analyse, Ltée, Montréal, Québec, Canada.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Robitaille
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Frank
authors.initials: F
authors.lastname: Albers
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Steve
authors.initials: S
authors.lastname: Yancey
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Hector
authors.initials: H
authors.lastname: Ortega
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Mark
authors.initials: M
authors.lastname: Forshag
authors.affiliation: 1 GlaxoSmithKline, Durham, North Carolina.
authors.forename: Xiwu
authors.initials: X
authors.lastname: Lin
authors.affiliation: 3 Groupe d'analyse, Ltée, Montréal, Québec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lefebvre
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents