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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

Lookup NU author(s): Mark Houseman, Dr Kate Potter, Nicola Marshall, Dr Rachel Lakey, Emeritus Professor Tim Cawston, Dr Steven Young-Min, Professor John IsaacsORCiD



Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

Publication metadata

Author(s): Houseman M, Potter C, Marshall N, Lakey R, Cawston T, Griffiths I, Young-Min S, Isaacs JD

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2012

Volume: 14

Issue: 1

Print publication date: 07/02/2012

Date deposited: 21/03/2013

ISSN (print): 1478-6354

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd.


DOI: 10.1186/ar3734


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