title: MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy.
abstract: BACKGROUND
  The study was undertaken to assess the efficacy of methotrexate (MTX) monotherapy on the radiographic progression of individual rheumatoid arthritis (RA) patients, each of whom had received MTX monotherapy for 3 years with an option to change to biological disease-modifying anti-rheumatic drugs (bDMARDs). We also looked for predictors of radiographic non-progression in these patients.
  
  
  METHODS
  Rheumatoid patients (n = 161) were prospectively followed for 3 years while receiving low-dose MTX monotherapy unless disease was otherwise active and/or adverse events appeared. Their disease activity and radiographic progression were evaluated with reference to disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and other indices. The change in van der Heijde-modified total Sharp score per year (∆TSS) was assessed using probability plots, in which the patients were classified into the subgroups showing structural remission (REM; ∆TSS ≤0.5), radiographic progression (∆TSS >3) or rapid radiographic progression (RRP; ∆TSS >5).
  
  
  RESULTS
  MTX monotherapy, continued until disease became active and/or adverse event appeared, was associated with a significant improvement (p <0.0001) in the DAS28-ESR (3) scores, % DAS28 remission, and mHAQ scores each year, from baseline to 3 years. The mHAQ remission rate (∆mHAQ <0.5) and Boolean remission were also improved from 16 to 60 % and 0.8 to 24.0 %, respectively. We found that the ratio of patients classified as REM increased yearly from 62/161 (38.5 %) to 69/137 (50.4 %), while those classified as ∆TSS >3 decreased from 55/161 (34.2 %) to 28/137 (20.4 %) and those in RRP decreased from 35/161 (21.7 %) to 15/137 (10.9 %). Receiver operating characteristic (ROC) curve analyses showed that serum matrix metalloproteinase-3 (MMP-3) <103.7 ng/ml at outset predicts a patient subgroup that exhibits no radiographic progression.
  
  
  CONCLUSIONS
  Half of rheumatoid patients treated with MTX monotherapy for 3 years exhibited structural remission, and this outcome can be predicted at the outset by lower serum MMP-3.
authors.affiliation: The Rheumatic Diseases Center, Kohnan Kakogawa Hospital, 1545-1 Saijo, Kannocho, Kakogawa, 675-8545, Japan. ka_k.shiozawa@kohnan.or.jp.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shiozawa
authors.affiliation: The Rheumatic Diseases Center, Kohnan Kakogawa Hospital, 1545-1 Saijo, Kannocho, Kakogawa, 675-8545, Japan. ka_t.yamane@kohnan.or.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamane
authors.affiliation: The Rheumatic Diseases Center, Kohnan Kakogawa Hospital, 1545-1 Saijo, Kannocho, Kakogawa, 675-8545, Japan. ka_m.murata@kohnan.or.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Murata
authors.affiliation: The Rheumatic Diseases Center, Kohnan Kakogawa Hospital, 1545-1 Saijo, Kannocho, Kakogawa, 675-8545, Japan. ka_r.yoshihara@kohnan.or.jp.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Yoshihara
authors.affiliation: Department of Medicine, Rheumatic Diseases Unit, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan. tsumiyama@beppu.kyushu-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Tsumiyama
authors.affiliation: The Rheumatic Diseases Center, Kohnan Kakogawa Hospital, 1545-1 Saijo, Kannocho, Kakogawa, 675-8545, Japan. ka_s.imura@kohnan.or.jp.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Imura
authors.affiliation: Department of Medicine, Rheumatic Diseases Unit, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan. shiozawa@beppu.kyushu-u.ac.jp.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shiozawa
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012074:Remission Induction; D012680:Sensitivity and Specificity
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D008727:Methotrexate