Article Text

THU0249 Early Therapeutic Intervention with Methotrexate (MTX) Prevents Development of Rheumatoid Arthritis (RA) in Patients with Undifferentiated Arthritis (UA), Even in the Presence of Smoking or the HLA-DR B1-Shared Epitope
  1. E.K. Tanaka1,
  2. M. Katayama1,
  3. T. Satoru1,
  4. M. Yoshimura1,
  5. A. Watanabe1,
  6. S. Tsuji1,
  7. H. Tsuboi1,
  8. M. Hirao1,
  9. A. Yura2,
  10. Y. Harada2,
  11. Y. Katada2,
  12. M. Matsushita1,
  13. J. Hashimoto1,
  14. S. Oshima3,
  15. Y. Saeki3
  1. 1Rheumatology
  2. 2Allergology
  3. 3Clinical Research, NHO Osaka Minami Medical Center, Osaka, Japan


Background Previously we reported that the patients with early-onset UA (EUA) showing high-titer anti-citrullinated peptide antibodies (ACPA) (>15 U/ml) developed RA within a year at high-rate (>80%) (ref. 1).

Objectives To examine whether early therapeutic intervention with MTX can prevent development of RA in patients with EUA who show high-titers of ACPA and to determine whether the effectiveness of treatment is modulated by risk factors associated with RA-onset, such as smoking or HLA-DRB1 shared epitope (SE).

Methods A prospective controlled study was conducted with 48 EUA patients who showed high-titers of ACPA and who had never been treated with any non-biologic DMARDs or biologics. All patients fulfilled with the 1994 Japan College of Rheumatology (JCR) criteria for early RA (ref. 2) but not the 1987 American College of Rheumatology (ACR) criteria for RA. Based on their decisions, one group was treated with MTX concomitant with corticosteroid (PSL<10mg/day) and/or NSAID (MTX+ Group, n=29). The other was treated without MTX (MTX- Group, n=19). The primary endpoint was development of RA as defined by fulfilling the 1987 ACR-criteria within one year after entry. To assess the effectiveness of the treatments (MTX+/−) while taking several risk factors into account, we used multivariate logistic regression analysis and the Cochran-Mantel-Haenszel test. Additionally, bone progression was assessed by the modified Sharp/Van der Heijde score (SHS). Adverse events (AEs) were recorded during endpoint or until one year.

Results The MTX+ Group developed RA at a significantly lower rate (17.2%) than the MTX- Group (78.9%) (p<0.001). Multivariate logistic regression analysis showed that regardless of RA-background factor, MTX treatment significantly prevented the development of RA (P=0.026). Then, we factored treatment Group (MTX+/−), smoking or HLA-DRB1 SE into a Cochran-Mantel-Haenszel test. Results showed that, despite positive smoking or HLA-DRB1 SE, intervention with MTX significantly prevented the development of RA (smoking, P<0.001; HLA-DRB1 SE, P<0.001). Although the mean interval changes from the baseline of the SHS per year did not significantly differ between the two groups, the number of patients without obvious radiographical progression was relatively higher in the MTX+ Group.In addition, there were no particular findings regarding to AEs.

Conclusions Early therapeutic intervention with MTX prevents RA development in patients who are very likely to develop RA within a year some regardless of the presence of smoking or HLA-DRB1 SE.


  1. Kudo-Tanaka E, Oshima S, Ishii M, et al. Autoantibodies to cyclic citrullinated peptide 2 (CCP2) are superior to other potential diagnostic biomarkers for predicting rheumatoid arthritis in early undifferentiated arthritis. Clin Rheumatol 2007; 26:1627-33.

  2. Yamamoto S, Kashiwazaki S, Nobunaga T. Study on Japanese Rheumatism Association diagnostic criteria for early rheumatoid arthritis –|2. Proposed diagnostic criteria for early rheumatoid arthritis. Ryumachi 1994; 34:1013-8.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.3121

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.