title: A multi-parameter response prediction model for rituximab in rheumatoid arthritis.
abstract: To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters.
  
  
  
  In two independent cohorts of 93 (cohort I) and 133 (cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28)≥1.8 after 6 months of therapy were considered responders.
  
  
  
  The mean IFN score was higher in non-responders compared to responders in both cohorts, but this difference was most pronounced in patients who did not use prednisone, as described before. Univariate analysis in cohort I showed that baseline DAS28, IFN score, DMARD use and negativity for IgM-RF and/or ACPA were associated with rituximab non-response. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. In cohort II, this model revealed a comparable AUC in PREDN-negative patients (0.78), but AUC in PREDN-positive patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone.
  
  
  
  Combination of predictive parameters provided a promising model for the prediction of non-response to rituximab, with possibilities for optimization via definition of the exact interfering effect of prednisone on IFN score.
  
  
  
  NCT01126541, registered 18 May 2010.
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands. Electronic address: td.dejong@vumc.nl.
authors.forename: Tamarah D
authors.initials: TD
authors.lastname: de Jong
authors.affiliation: Inserm UMRS_938, DHU i2B, rheumatology department, Saint-Antoine hospital, université Paris 06, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands; Amsterdam rheumatology and immunology center, location Reade, P.O. box 58271, 1040HG Amsterdam, The Netherlands.
authors.forename: Rabia
authors.initials: R
authors.lastname: Agca
authors.affiliation: Department of pathology, VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Vosslamber
authors.affiliation: Department of epidemiology and biostatistics, VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: Tsang-A-Sjoe
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Elise
authors.initials: E
authors.lastname: Mantel
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands; Amsterdam rheumatology and immunology center, location Reade, P.O. box 58271, 1040HG Amsterdam, The Netherlands.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.affiliation: Amsterdam rheumatology and immunology center, location VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands; Amsterdam rheumatology and immunology center, location Reade, P.O. box 58271, 1040HG Amsterdam, The Netherlands.
authors.forename: Mike T
authors.initials: MT
authors.lastname: Nurmohamed
authors.affiliation: Department of pathology, VU university medical center, P.O. box 7057, 1007MB Amsterdam, The Netherlands.
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Verweij
authors.affiliation: Inserm U1184, rheumatology department, center for immunology of viral infections and autoimmune diseases, hôpitaux universitaires Paris-Sud, université Paris-Sud, AP-HP, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000367:Age Factors; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005602:France; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D018570:Risk Assessment; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D016898:Interferon-alpha; D000069283:Rituximab
keywords: Prediction; Rheumatoid arthritis; Rituximab; Type I interferon