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

Gia Deyab, Ingrid Hokstad, Jon Elling Whist, Milada Cvancarova Smastuen, Stefan Agewall, Torstein Lyberg, Nicoletta Ronda, Knut Mikkelsen, Gunnbjorg Hjeltnes, Ivana Hollan, Gia Deyab, Ingrid Hokstad, Jon Elling Whist, Milada Cvancarova Smastuen, Stefan Agewall, Torstein Lyberg, Nicoletta Ronda, Knut Mikkelsen, Gunnbjorg Hjeltnes, Ivana Hollan

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.

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

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