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Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year

Jonathan Kay1*, Olga Morgacheva2, Susan P Messing3, Joel M Kremer4, Jeffrey D Greenberg5, George W Reed6, Ellen M Gravallese1 and Daniel E Furst2

Author Affiliations

1 Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Medical Center, 119 Belmont Street, Worcester, MA 01605, USA

2 Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA

3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA

4 Division of Rheumatology, Department of Medicine, Albany Medical College and the Center for Rheumatology, 1367 Washington Avenue, Albany, NY 12203, USA

5 Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10003, USA

6 The Consortium of Rheumatology Researchers of North America, Inc. (CORRONA), 10 Vickery Hill Lane, Southborough, MA 01772, USA

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Arthritis Research & Therapy 2014, 16:R40  doi:10.1186/ar4469

Published: 3 February 2014



Clinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels.


This was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was >2.8 (not in remission).


Of 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline.


In a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial visit. Requiring an elevation in APR levels as a criterion for inclusion of RA patients in studies of experimental agents may exclude some patients with active disease.