Endothelial Function Improves With Methotrexate, Anti-TNF Therapy in Inflammatory Arthritis

In patients with inflammatory arthritis (IA)—which includes rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)—treatment with methotrexate (MTX) monotherapy and antitumor necrosis factor (anti-TNF) with or without MTX was associated with a relatively rapid improvement in endothelial function (EF), according to the results of a recent observational Norwegian study (ClinicalTrials.gov Identifier: NCT00902005) published in Arthritis Research & Therapy.

The investigators evaluated 113 patients from the Psoriatic arthritis, Ankylosing spondylitis, Rheumatoid Arthritis (PSARA) study who had completed 6 months of follow-up. Endothelial function was assessed in all patients: 64 with RA, 29 with PsA, and 20 with AS. In patients who had endothelial dysfunction at baseline (n=40), changes in the Reactive Hyperemic Index (RHI) after 6 weeks and 6 months of antirheumatic therapy were evaluated.

In patients with IA and endothelial dysfunction, RHI improved significantly from baseline to 6 weeks of treatment (MTX monotherapy: P =.002; anti-TNF ± MTX: P =.004) and from baseline to 6 months of treatment (MTX monotherapy: P =.001; anti-TNF ± MTX: P =.024), regardless of changes in disease activity parameters. Upon analysis of all 3 groups with endothelial dysfunction, only patients with RA demonstrated statistically significant RHI improvements from baseline to 6 weeks (RHI at 6 weeks=1.96; P <.001) and from baseline to 6 months (RHI at 6 months=1.86; P =.001). None of the RHI changes in the AS or PsA groups achieved statistical significance.

After 6 months, improvements in RHI were greater in the MTX-alone group than in the
anti-TNF ± MTX group, with the difference remaining significant after adjustment for potential confounders. In those with active RA, AS, and PsA, patients with AS appeared to have the worst endothelial function, although they were also the youngest individuals to be evaluated.

The investigators concluded that treatment with MTX monotherapy and anti-TNF ± MTX was linked to a relatively fast improvement in endothelial function in patients with IA and endothelial dysfunction. After 6 months, improvements in endothelial function were more pronounced among MTX users than among anti-TNF ± MTX users. It is possible that modes of action other than an anti-inflammatory effect may contribute to the improvements in endothelial function that were observed.

Reference

Deyab G, Hokstad I, Whist JE, et al. Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis. Arthritis Res Ther. 2017;19(1):232.