title: Serious adverse effects associated with glucocorticoid therapy in patients with giant cell arteritis (GCA): A nested case-control analysis.
abstract: Giant cell arteritis (GCA) is an inflammatory vasculitis preferentially affecting large and medium-sized arteries. High-dose oral glucocorticoids (GCs) are the mainstay of GCA therapy. Using data from the UK Clinical Practice Research Datalink (CPRD), we examined the risk of oral GC-related serious adverse events (SAEs) in a UK population of patients with giant cell arteritis (GCA).
  
  
  
  We conducted a series of nested case-control analyses in GCA patients to examine the effect of increasing dose of prednisolone on the risk of developing diabetes, glaucoma, osteoporosis, fractures, serious infection requiring hospitalization, and death. We used conditional logistic regression to calculate the unadjusted and multivariate odds ratios (ORs) with 95% CIs for the associations between prednisolone use and the risks of all outcomes of interest. We stratified the analyses by increasing cumulative prednisolone use and average daily dose.
  
  
  
  In the multivariate analyses, we observed a trend of increasing risk of diabetes and osteoporosis with increasing cumulative dose of oral prednisolone (ptrend< 0.05). GCA patients in the highest daily dose category (30mg/d) had an increased risk of diabetes (adjusted OR, 95% CI) (4.7, 2.8-7.8), osteoporosis (1.9, 1.2-2.9), fractures (2.6, 1.6-4.3), glaucoma (3.5, 2.0-6.1), serious infection (3.3, 2.2-5.2), and death (2.1, 1.3-3.5) compared to those with lower average daily prednisolone doses (5mg/d).
  
  
  
  Compared to lower average daily prednisolone doses, high average daily doses were associated with an increased risk of serious adverse effects.
authors.affiliation: Basel Pharmacoepidemiology Unit, Hospital Pharmacy, University of Basel, Basel, Switzerland.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Wilson
authors.affiliation: Genentech, Inc, South San Francisco, CA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Sarsour
authors.affiliation: Roche Products Ltd, Welwyn Garden City, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Collinson
authors.affiliation: Roche Products Ltd, Welwyn Garden City, United Kingdom.
authors.forename: Katie
authors.initials: K
authors.lastname: Tuckwell
authors.affiliation: Genentech, Inc, South San Francisco, CA.
authors.forename: David
authors.initials: D
authors.lastname: Musselman
authors.affiliation: Genentech, Inc, South San Francisco, CA.
authors.forename: Micki
authors.initials: M
authors.lastname: Klearman
authors.affiliation: Genentech, Inc, South San Francisco, CA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Napalkov
authors.affiliation: Boston Collaborative Drug Surveillance Program (BCDSP), Boston University School of Public Health, Lexington, MA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Jick
authors.affiliation: Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston, MA.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.affiliation: Basel Pharmacoepidemiology Unit, Hospital Pharmacy, University of Basel, Basel, Switzerland; Boston Collaborative Drug Surveillance Program (BCDSP), Boston University School of Public Health, Lexington, MA; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland. Electronic address: Christoph.Meier@usb.ch.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Meier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D013700:Giant Cell Arteritis / Q000188:drug therapy*; D005901:Glaucoma / Q000139:chemically induced* / Q000453:epidemiology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced* / Q000453:epidemiology; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone
keywords: Giant cell arteritis; Glucocorticoids; Health services research; Outcomes research; Serious adverse events