title: In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis.
abstract: BACKGROUND
  Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.
  
  
  METHODS
  Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).
  
  
  RESULTS
  GR number was positively correlated with improvement in DAS. IL-2-EC₅₀ and GILZ-EC₅₀ values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC₅₀ values and higher GR number and KD.
  
  
  CONCLUSIONS
  Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.
authors.forename: Rogier A M
authors.initials: RA
authors.lastname: Quax
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.forename: Pascal H P
authors.initials: PH
authors.lastname: de Jong
authors.forename: Ramona
authors.initials: R
authors.lastname: van Heerebeek
authors.forename: Angelique E
authors.initials: AE
authors.lastname: Weel
authors.forename: Anne M
authors.initials: AM
authors.lastname: Huisman
authors.forename: Derkjen
authors.initials: D
authors.lastname: van Zeben
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D011241:Prednisone; D008775:Methylprednisolone