Clinical and epidemiological research ▶ Additional tables are published online only. To view these Þles please visit the journal online (http://dx.doi.org/10.1136/ annrheumdis-2011-200963) 1Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands 2Department of Informatics, Crescendo Bioscience, South San Francisco, California, USA 3Department of Development, Crescendo Bioscience, South San Francisco, California, USA 4Department of Microbiology and Immunology OMRF, Oklahoma City, Oklahoma, USA 5Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands Correspondence to Marije F Bakker, UMC Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht PO BOX 85500, The Netherlands; m.f.bakker-8@umcutrecht.nl Accepted 23 February 2012 1692 annrheumdis-2011-200963.indd 1 EXTENDED REPORT Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study Marije F Bakker,1 Guy Cavet,2 Johannes WG Jacobs,1 Johannes W J Bijlsma,1 Douglas J Haney,2 Yijing Shen,2 Lyndal K Hesterberg,3 Dustin R Smith,3 Michael Centola,4 Joel A G van Roon,1 Floris P J G Lafeber,1 Paco M J Welsing,1,5 ABSTRACT Objectives To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA) patient population from the computer assisted management in early rheumatoid arthritis (CAMERA) study. Methods Twenty biomarkers were measured in the CAMERA cohort, in which patients were treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA score was calculated using the concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained algorithm. The performance of the scores was evaluated relative to clinical disease activity assessments. Change in MBDA score over time was assessed by paired Wilcoxon rank sum test. Logistic regression was used to evaluate the ability of disease activity measures to predict radiographic progression. Results The MBDA score had a signiÞcant correlation with the disease activity score based on 28 joints-C reactive protein (DAS28-CRP) (r=0.72; p<0.001) and an area under the receiver operating characteristic curve for distinguishing remission/low from moderate/high disease activity of 0.86 (p<0.001) using a DAS28-CRP cut-off of 2.7. In multivariate analysis the MBDA score, but not CRP, was an independent predictor of disease activity measures. Additionally, mean (SD) MBDA score decreased from 53 (18) at baseline to 39 (16) at 6 months in response to study therapy (p<0.0001). Neither MBDA score nor clinical variables were predictive of radiographic progression. Conclusions This multi-biomarker test performed well in the assessment of disease activity in RA patients in the CAMERA study. Upon further validation, this test could be used to complement currently available disease activity measures and improve patient care and outcomes. INTRODUCTION Rheumatoid arthritis (RA) is a chronic inﬂamma- tory disease causing joint pain and destruction of joints, with resulting functional disability.1 When treating RA, minimising inﬂammation over a patient’s lifetime is important to reduce functional disability and improve quality of life. This can be achieved by a concept, known as ‘tight control’.2–5 Current recommendations for treatment of RA advise measuring disease activity as frequently as monthly for patients with moderate-to-high dis- ease activity, and less frequently, such as every 3–6 months, for patients with sustained low disease activity or remission.4 In the computer assisted management in early rheumatoid arthritis (CAMERA) study, subjects with early RA were randomly assigned to either an intensive or a conventional management strategy.6 7 The intensive strategy employed tight control, using more frequent follow-up and intensive ther- apy with methotrexate (MTX) according to a strict protocol as supported by a computerised decision program based on disease activity measurements with the aim of reaching remission. After 2 years of treatment, subjects in the intensive strategy group achieved remission more often, more rapidly and for a longer period of time than subjects in the con- ventional strategy group.7 Currently, measurements of disease activity in the clinic may include symptom assessment, joint counts, individual laboratory tests (eg, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), or some combination of these in an index such as the disease activity score based on 28 joints (DAS28), Clinical Disease Activity Index, Simpliﬁed Disease Activity Index or Routine Assessment of Patient Index Data.8 9 The DAS28 and its variants (DAS, DAS28-CRP) are arguably the most exten- sively validated and accepted composite measures of RA disease activity. They combine three direct measurements of patient status (swollen joint count (SJC), tender joint count (TJC) and visual analogue scale general health (VAS-GH)) with one surrogate measure of inﬂammation (ESR or CRP).9 10 While the value of such measures has been rigor- ously demonstrated, they have limitations. Clinical assessments depend upon patient and/or physi- cian judgments and are subject to intra-assessor and inter-assessor variability,11–13 while laboratory tests such as ESR and CRP are general measures of inﬂammation and can be in the normal range in approximately 40% of RA patients.14 15 In principle, biomarkers have the potential to provide objective measurements of the disease processes underlying RA. Numerous individual biomarkers have been shown to be associated with disease activity, and a recent study suggests that applying the tight control principle to biomarkers Ann Rheum Dis 2012;71:1692–1697. doi:10.1136/annrheumdis-2011-200963 8/23/2012 3:34:16 AM