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Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up

Mark Houseman1, Catherine Potter1, Nicola Marshall2, Rachel Lakey1, Tim Cawston1, Ian Griffiths2, Steven Young-Min3* and John D Isaacs12

Author Affiliations

1 Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, 4th Floor Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

2 Musculoskeletal Services, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne, NE7 7DN, UK

3 Rheumatology, Queen Alexandra Hospital, Southwick Hill Road, Portsmouth, PO6 3LY, UK

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Arthritis Research & Therapy 2012, 14:R30  doi:10.1186/ar3734

Published: 7 February 2012



At present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). We previously demonstrated an association between specific baseline biomarkers/clinical measures including matrix metalloproteinase-3 (MMP-3) and 2-year radiographic progression in patients with RA. This study further evaluates the predictive capability of these baseline variables with outcome extended over 8-years.


Fifty-eight of the original cohort (n = 118) had radiographic progression from baseline to mean 8.2-years determined using the van der Heijde modified Sharp method. The contribution of each predictor variable towards radiographic progression was assessed with univariate and multivariate analyses.


Traditional factors (including erythrocyte sedimentation rate, C-reactive protein, anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor) and biomarkers of tissue destruction (including MMP-3, C-telopeptide of type II collagen, cartilage oligomeric matrix protein, and tissue inhibitor of metalloproteinase 1) measured at baseline were associated with radiographic progression at endpoint. Multivariate logistic regression identified anti-CCP seropositivity [OR 9.29, 95%CI: 2.29-37.64], baseline elevated MMP-3 [OR 8.25, 95%CI: 2.54-26.78] and baseline radiographic damage [OR 5.83, 95%CI: 1.88-18.10] as the strongest independent predictors of radiographic progression. A model incorporating these variables had a predictive accuracy of 0.87, assessed using the area under the receiver operating characteristic curve.


In our cohort with onset of RA symptoms < 2-years, multivariate analysis identified anti-CCP status and baseline MMP-3 as the strongest independent predictors of radiographic disease outcome at 8.2-years. This finding suggests determination of baseline MMP-3, in conjunction with traditional serologic markers, may provide additional prognostic information for patients with RA. Furthermore, these findings highlight the importance of continued research into a broad range of biomarkers as potential predictors of joint damage.