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.
BACKGROUND
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.


CONCLUSIONS
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.
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.
Mark
M
Houseman
Catherine
C
Potter
Nicola
N
Marshall
Rachel
R
Lakey
Tim
T
Cawston
Ian
I
Griffiths
Steven
S
Young-Min
John D
JD
Isaacs
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D019370:Observation; D011237:Predictive Value of Tests; D011379:Prognosis; D011859:Radiography; D013997:Time Factors
D015415:Biomarkers; D019278:Matrix Metalloproteinase 3