title: Effect of prednisone on type I interferon signature in rheumatoid arthritis: consequences for response prediction to rituximab.
abstract: BACKGROUND
  Elevated type I interferon (IFN) response gene (IRG) expression has proven clinical relevance in predicting rituximab non-response in rheumatoid arthritis (RA). Interference between glucocorticoids (GCs) and type I IFN signaling has been demonstrated in vitro. Since GC use and dose are highly variable among patients before rituximab treatment, the aim of this study was to determine the effect of GC use on IRG expression in relation to rituximab response prediction in RA.
  
  
  METHODS
  In two independent cohorts of 32 and 182 biologic-free RA patients and a third cohort of 40 rituximab-starting RA patients, peripheral blood expression of selected IRGs was determined by microarray or quantitative real-time polymerase chain reaction (qPCR), and an IFN-score was calculated. The baseline IFN-score was tested for its predictive value towards rituximab response in relation to GC use using receiver operating characteristics (ROC) analysis in the rituximab cohort. Patients with a decrease in disease activity score (∆DAS28) >1.2 after 6 months of rituximab were considered responders.
  
  
  RESULTS
  We consistently observed suppression of IFN-score in prednisone users (PREDN(+)) compared to non-users (PREDN(-)). In the rituximab cohort, analysis on PREDN(-) patients (n = 13) alone revealed improved prediction of rituximab non-response based on baseline IFN-score, with an area under the curve (AUC) of 0.975 compared to 0.848 in all patients (n = 40). Using a group-specific IFN-score cut-off for all patients and PREDN(-) patients alone, sensitivity increased from 41% to 88%, respectively, combined with 100% specificity.
  
  
  CONCLUSIONS
  Because of prednisone-related suppression of IFN-score, higher accuracy of rituximab response prediction was achieved in PREDN(-) patients. These results suggest that the IFN-score-based rituximab response prediction model could be improved upon implementation of prednisone use.
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7075, 1007, MB, Amsterdam, The Netherlands. td.dejong@vumc.nl.
authors.forename: Tamarah D
authors.initials: TD
authors.lastname: de Jong
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7075, 1007, MB, Amsterdam, The Netherlands. s.vosslamber@vumc.nl.
authors.forename: Saskia
authors.initials: S
authors.lastname: Vosslamber
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7075, 1007, MB, Amsterdam, The Netherlands. m.blits@vumc.nl.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Blits
authors.affiliation: Jan van Breemen Institute | Reade, Amsterdam, The Netherlands. g.wolbink@reade.nl.
authors.forename: Gertjan
authors.initials: G
authors.lastname: Wolbink
authors.affiliation: Jan van Breemen Institute | Reade, Amsterdam, The Netherlands. m.nurmohamed@reade.nl.
authors.forename: Mike T
authors.initials: MT
authors.lastname: Nurmohamed
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. j.vanderlaken@vumc.nl.
authors.forename: Conny J
authors.initials: CJ
authors.lastname: van der Laken
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. g.jansen@vumc.nl.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Jansen
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. ae.voskuyl@vumc.nl.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7075, 1007, MB, Amsterdam, The Netherlands. c.verweij@vumc.nl.|Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. c.verweij@vumc.nl.
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use*; D000069283:Rituximab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007370:Interferon Type I; D000069283:Rituximab; D011241:Prednisone