Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis

Arthritis Res Ther. 2017 Oct 17;19(1):232. doi: 10.1186/s13075-017-1439-1.


Background: Inflammatory arthritis (IA), including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), leads to increased cardiovascular disease occurrence probably due to atherosclerosis. One of the first stages in atherogenesis is endothelial dysfunction (ED). Therefore, we aimed to compare endothelial function (EF) in patients with IA, and to examine the effects of methotrexate (MTX) monotherapy and antitumor necrosis factor (anti-TNF) treatment with or without MTX comedication (anti-TNF ± MTX) on EF.

Methods: From the PSARA observational study, all patients with RA (n = 64), PsA (n = 29), and AS (n = 20) were evaluated for EF. In patients with ED at baseline (n = 40), we evaluated changes in the Reactive Hyperemic Index (RHI) after 6 weeks and 6 months of antirheumatic therapy.

Results: In IA patients with ED, RHI significantly improved after 6 weeks (p < 0.001) and 6 months (p < 0.001) of treatment, independent of changes in disease activity parameters. After 6 months, RHI had improved more in the MTX group than in the anti-TNF ± MTX group, and the difference remained statistically significant after adjustments for potential confounders. Among patients with active RA, AS, and PsA, those with AS appeared to have the worst endothelial function, although they were the youngest.

Conclusion: Treatment with MTX and anti-TNF ± MTX was associated with a relatively fast improvement of EF in IA patients with ED, independent of change in disease activity. Therefore, modes of action other than the anti-inflammatory effect may contribute to the EF improvement. After 6 months, the EF improvement was more pronounced in the MTX group than in the anti-TNF ± MTX group.

Trial registration: Clinicaltrials, NCT00902005 . Registered on 13 May 2009.

Keywords: Anti-tumor necrosis factor; Inflammatory arthritis; Methotrexate; Rheumatic arthritis; Spondyloarthritis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Hyperemia
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Spondylitis, Ankylosing / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Methotrexate

Associated data