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Research ArticleArticle
Open Access

A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study

Iris M. Markusse, Linda Dirven, Marianne van den Broek, Casper Bijkerk, K. Huub Han, H. Karel Ronday, Rebecca Bolce, Eric H. Sasso, Pit J.S.M. Kerstens, Willem F. Lems, Tom W.J. Huizinga and Cornelia F. Allaart
The Journal of Rheumatology August 2014, jrheum.131412; DOI: https://doi.org/10.3899/jrheum.131412
Iris M. Markusse
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Linda Dirven
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Marianne van den Broek
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Casper Bijkerk
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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K. Huub Han
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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H. Karel Ronday
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Rebecca Bolce
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Eric H. Sasso
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Pit J.S.M. Kerstens
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Willem F. Lems
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Tom W.J. Huizinga
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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Cornelia F. Allaart
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. Supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. No financial support from Crescendo Bioscience. 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. Address correspondence to Dr. I.M. Markusse, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m.markusse@lumc.nl. Full Release Article. For details see Reprints/Permissions at jrheum.org. Accepted for publication June 4, 2014.
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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.

Conclusion MBDA scores predict radiographic damage progression at baseline and during disease course.

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A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study
Iris M. Markusse, Linda Dirven, Marianne van den Broek, Casper Bijkerk, K. Huub Han, H. Karel Ronday, Rebecca Bolce, Eric H. Sasso, Pit J.S.M. Kerstens, Willem F. Lems, Tom W.J. Huizinga, Cornelia F. Allaart
The Journal of Rheumatology Aug 2014, jrheum.131412; DOI: 10.3899/jrheum.131412

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A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study
Iris M. Markusse, Linda Dirven, Marianne van den Broek, Casper Bijkerk, K. Huub Han, H. Karel Ronday, Rebecca Bolce, Eric H. Sasso, Pit J.S.M. Kerstens, Willem F. Lems, Tom W.J. Huizinga, Cornelia F. Allaart
The Journal of Rheumatology Aug 2014, jrheum.131412; DOI: 10.3899/jrheum.131412
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