title: Early therapeutic intervention with methotrexate prevents the development of rheumatoid arthritis in patients with recent-onset undifferentiated arthritis: A prospective cohort study.
abstract: OBJECTIVE
  To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers.
  
  
  METHODS
  The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year.
  
  
  RESULTS
  The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups.
  
  
  CONCLUSIONS
  This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.
authors: a Department of Clinical Research , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.|b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Eriko
authors: E
authors: Kudo-Tanaka
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Takashi
authors: T
authors: Shimizu
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Takuro
authors: T
authors: Nii
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Satoru
authors: S
authors: Teshigawara
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Maiko
authors: M
authors: Yoshimura
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Akane
authors: A
authors: Watanabe
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Soichiro
authors: S
authors: Tsuji
authors: c Department of Orthopedics , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Hideki
authors: H
authors: Tsuboi
authors: c Department of Orthopedics , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Makoto
authors: M
authors: Hirao
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Akiko
authors: A
authors: Yura
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Yoshinori
authors: Y
authors: Harada
authors: d Department of Rheumatology , NHO Shimoshizu National Hospital , Yotsukaido, Chiba , Japan.
authors: Makoto
authors: M
authors: Sueishi
authors: e Department of Rheumatology , NHO Beppu Medical Center , Beppu, Oita , Japan.
authors: Yasuo
authors: Y
authors: Suenaga
authors: f Department of Rheumatology , NHO Morioka National Hospital , Morioka, Miyagi , Japan.
authors: Noriyuki
authors: N
authors: Chiba
authors: g Department of Orthopedics , NHO Zentsuji National Hospital , Zentsuji, Kagawa , Japan.
authors: Takeharu
authors: T
authors: Tonai
authors: h Department of Rheumatology , NHO Miyakonojo National Hospital , Miyakonojo, Miyazaki , Japan.
authors: Koichiro
authors: K
authors: Saisho
authors: i Department of Respiratory Medicine , Allergology and Rheumatic Disease, Osaka University Graduate School of Medicine , Osaka , Japan.
authors: Atsushi
authors: A
authors: Ogata
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Masato
authors: M
authors: Matsushita
authors: b Department of Rheumatology and Allergology , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Jun
authors: J
authors: Hashimoto
authors: a Department of Clinical Research , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Shiro
authors: S
authors: Ohshima
authors: j Department of Rheumatology , NHO Sagamihara National Hospital , Sagamihara, Kanagawa , Japan.
authors: Shigeto
authors: S
authors: Tohma
authors: a Department of Clinical Research , NHO Osaka Minami Medical Center , Kawachinagano, Osaka , Japan.
authors: Yukihiko
authors: Y
authors: Saeki
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D000939:Epitopes; D008727:Methotrexate
keywords: Anti-citrullinated peptide antibody; Methotrexate; Recent-onset undifferentiated arthritis; Rheumatoid arthritis