title: Continuously elevated serum matrix metalloproteinase-3 for 3 ~ 6 months predict one-year radiographic progression in rheumatoid arthritis: a prospective cohort study.
abstract: BACKGROUND
  Core disease activity indicators of rheumatoid arthritis (RA) have been found to be limited in predicting joint destruction progression. Matrix metalloproteinase (MMP) 3 plays an essential role in joint destruction and was found elevated in some remission patients. We aimed to monitor dynamic core disease activity indicators and serum MMP-3 for one year and evaluate their value for predicting radiographic progression.
  
  
  METHODS
  Patients with active RA (Simplified disease activity index > 3.3) were treated according to the treat-to-target strategy. Serum MMP-3 was detected by enzyme-linked immunosorbent assay and clinical data were collected simultaneously at 0, 1st, 3rd, 6th and 12th month. X-ray assessment of hand/wrist was repeated at baseline and the 12th month and a change of total Sharp score > 0.5 units was defined as radiographic progression.
  
  
  RESULTS
  Fifty-six patients completed one year follow-up and 29 % showed radiographic progression. Although not significantly different at baseline, serum MMP-3 and all core disease activity indicators, except for erythrocyte sedimentation rate, at the 12th month were significantly higher in the progressive group than in the non-progressive group. Among sixteen progressive patients, 69 % achieved the therapeutic target and 56 % had continuous elevated serum MMP-3, 38 % had continuous elevated serum MMP-3 and normal C-reactive protein (CRP) at the 6th month. Log-rank tests and repeated measures analysis revealed a significant difference in dynamic serum MMP-3 between progressive and non-progressive patients. Receiver operating characteristic curve and univariate logistic regression analysis showed that elevated serum MMP-3 at 0, 1st, 3rd and 6th months, compared with CRP at the 1st month, were significant predictors for one-year radiographic progression (MMP-3 odds ratio (OR):10.500 ~ 27.000, all P < 0.05; CRP: OR = 7.400, P = 0.011).
  
  
  CONCLUSIONS
  Our data showed that continuously elevated serum MMP-3 for 3 ~ 6 months predicted one-year radiographic progression which implied that monitoring of dynamic serum MMP-3 combined with core disease activity indicators may be more helpful for predicting radiographic progression and treatment decision in RA.
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. majianda@139.com.
authors.forename: Jian-Da
authors.initials: JD
authors.lastname: Ma
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. wxning0814@163.com.
authors.forename: Xiu-Ning
authors.initials: XN
authors.lastname: Wei
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. zhengouyang@sina.com.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. Toqianye@163.com.
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Mo
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. 754318863@qq.com.
authors.forename: Le-Feng
authors.initials: LF
authors.lastname: Chen
authors.affiliation: Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. XiangZ2007@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3800, Australia. jinhua.li@monash.edu.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Li
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. liedai2004@163.com.
authors.forename: Lie
authors.initials: L
authors.lastname: Dai
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000201:enzymology; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D011859:Radiography; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3