Abstract
IntroductionAt 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.MethodsFifty-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.ResultsTraditional 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.ConclusionIn 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.
Highlights
At present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA)
Division of the cohort based on radiographic progression at 8.2 years Fifty-eight (49%) patients from the original cohort were analysed in the extension study
Predictors of radiographic progression at 8.2 years Mann Whitney analysis of traditional markers indicated that high radiographic progressors had significantly elevated measures of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Sharp scoring (SHS) and clinician’s global
Summary
There is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). Current paradigms for management of patients with rheumatoid arthritis (RA) dictate early aggressive therapy in treatment-to-target strategies, aiming for remission of symptoms [1] In turn this prevents joint destruction and algorithms, while predictive at a population level, have insufficient power to guide treatment of the individual patient [2]. Some baseline clinical and demographic markers (e.g. female sex, older age, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) seropositivity, raised Creactive protein (CRP) or erythrocyte sedimentation rate (ESR)) have been associated with a poor prognosis [3]. None of these markers reflect ongoing destructive processes within bone and synovium. These findings suggest that assessment of baseline MMP-3 and other biomarkers of joint destruction, in conjunction with existing serological markers and clinical measures, may provide additional long-term prognostic information for patients with RA
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