title: A multibiomarker disease activity score for rheumatoid arthritis predicts radiographic joint damage in the BeSt study.
abstract: OBJECTIVE
  To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.
  
  
  METHODS
  There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable.
  
  
  RESULTS
  At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH≥5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639-0.896] than did DAS (AUC 0.521, 95% CI 0.358-0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453-0.929) and DAS had an AUC of 0.649 (95% CI 0.417-0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018-1.059 for baseline MBDA score; 1.037, 95% CI 1.009-1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score.
  
  
  CONCLUSIONS
  MBDA scores predict radiographic damage progression at baseline and during disease course.
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center. i.m.markusse@lumc.nl.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Markusse
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Linda
authors.initials: L
authors.lastname: Dirven
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Marianne
authors.initials: M
authors.lastname: van den Broek
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Casper
authors.initials: C
authors.lastname: Bijkerk
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: K Huub
authors.initials: KH
authors.lastname: Han
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: H Karel
authors.initials: HK
authors.lastname: Ronday
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bolce
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Sasso
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Pit J S M
authors.initials: PJ
authors.lastname: Kerstens
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: From the Department of Rheumatology, Leiden University Medical Center, Leiden; Reinier de Graaf Hospital, Delft; Maasstad Hospital, Rotterdam; Haga Hospital, the Hague; Reade organization; VU Medical Center, Amsterdam, the Netherlands; Crescendo Bioscience, South San Francisco, California, USA.I.M. Markusse, MD; L. Dirven, PhD; M. van den Broek, MD, PhD, Department of Rheumatology, Leiden University Medical Center; C. Bijkerk, MD, PhD, Department of Rheumatology, Reinier de Graaf Hospital; K.H. Han, MD, Department of Rheumatology, Maasstad Hospital; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; R. Bolce, MSN; E.H. Sasso, MD, Crescendo Bioscience; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Reade; W.F. Lems, MD, PhD, Department of Rheumatology, Reade, and VU Medical Center; T.W.J. Huizinga, MD, PhD; C.F. Allaart, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
authors.forename: Cornelia F
authors.initials: CF
authors.lastname: Allaart
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000188:drug therapy; D001175:Arthrography / Q000379:methods; D015415:Biomarkers / Q000097:blood*; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009426:Netherlands; D016012:Poisson Distribution; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers
keywords: BIOMARKERS; MULTIBIOMARKER DISEASE ACTIVITY SCORE; PREDICTIVE VALUE OF TESTS; RADIOGRAPHIC JOINT DAMAGE PROGRESSION; RHEUMATOID ARTHRITIS