Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2017 Oct 17;19(1):232.
doi: 10.1186/s13075-017-1439-1.

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

Gia Deyab  1 , Ingrid Hokstad  2 , Jon Elling Whist  3   4 , Milada Cvancarova Smastuen  5 , Stefan Agewall  6   7 , Torstein Lyberg  8 , Nicoletta Ronda  9 , Knut Mikkelsen  2 , Gunnbjorg Hjeltnes  10 , Ivana Hollan  2   11   12   4
Affiliations
Observational Study

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

Gia Deyab et al. Arthritis Res Ther. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Authors' information

Not applicable

Ethics approval and consent to participate

The Norwegian Regional Ethical Committee approved the study protocol and all patients gave informed written consent.

Consent for publication

All patients gave informed written consent to publish.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
RHI values in RA, PsA, and AS patients with ED at all visits. *P < 0.05, versus baseline. The lines inside of the boxes show the median; the whiskers of the boxes show upper and lower values. AS ankylosing spondylitis, IA inflammatory arthritis, PsA psoriatic arthritis, RA rheumatoid arthritis, RHI Reactive Hyperemic Index
Fig. 2
Fig. 2
RHI values for patients with ED between and within the MTX and anti-TNF ± MTX groups. *P < 0.05 compared to baseline value. anti-TNF anti-tumor necrosis factor, MTX methotrexate, ns not statistically significant, RHI Reactive Hyperemic Index
See this image and copyright information in PMC

References

    1. Hollan I, Meroni PL, Ahearn JM, Cohen Tervaert JW, Curran S, Goodyear CS, et al. Cardiovascular disease in autoimmune rheumatic diseases. Autoimmun Rev. 2013;12(10):1004–15. doi: 10.1016/j.autrev.2013.03.013. - DOI - PubMed
    1. Boehncke WH, Boehncke S. Cardiovascular mortality in psoriasis and psoriatic arthritis: epidemiology, pathomechanisms, therapeutic implications, and perspectives. Curr Rheumatol Rep. 2012;14(4):343–8. doi: 10.1007/s11926-012-0260-8. - DOI - PubMed
    1. Gladman DD, Farewell VT, Wong K, Husted J. Mortality studies in psoriatic arthritis: results from a single outpatient center. II. Prognostic indicators for death. Arthritis Rheum. 1998;41(6):1103–10. doi: 10.1002/1529-0131(199806)41:6<1103::AID-ART18>3.0.CO;2-N. - DOI - PubMed
    1. Lehtinen K. Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis. 1993;52(3):174–6. doi: 10.1136/ard.52.3.174. - DOI - PMC - PubMed
    1. Han C, Robinson DW, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33(11):2167–72. - PubMed

Publication types

Associated data