Treatment with immunomodulators reduces adverse cardiovascular events

Several literature studies have linked inflammation to plaque rupture and adverse
atherosclerotic events. However, the effects of RA treatments on cardiovascular risk have not
been clearly elucidated. Now, a recent study published in the Annals of the Rheumatic
Diseases observed that adding tumor necrosis factor (TNF) inhibitors to methotrexate
improves vascular inflammation in rheumatoid arthritis (RA) patients.

Researchers from Brigham and Women’s Hospital conducted a trial among 115 RA patients
to study the impact of two anti-inflammatory treatment strategies. Patients were randomized
into two study groups to receive methotrexate with either a TNF inhibitor or sulfasalazine and
hydroxychloroquine (triple therapy) for 24 weeks. In both the groups, a significant reduction in
the target-to-background ratio in the carotid artery was noted [ΔTNF inhibitor: −0.24 (SD=0.51),
Δtriple therapy: −0.19 (SD=0.51)]. Experts also observed clinical improvements in vascular
inflammation in both groups. They found methotrexate with TNF inhibitors to be
superior to triple therapy in improving vascular inflammation, but not arterial inflammation.

A 2020 trial by Giles et al. compared the risk of major adverse cardiovascular events among
RA patients receiving tocilizumab and etanercept. The 4-week treatment demonstrated
a significant increase in serum low-density lipoprotein cholesterol (11.1%), triglyceride (5.7%),
and high-density lipoprotein cholesterol (13.6%) in the tocilizumab group than in the
etanercept group. The adverse events were also reported to be higher in the tocilizumab
group than etanercept.

Treatment-related increase in lipid parameters among RA patients receiving tocilizumab
raises a question about cardiovascular risk. Further investigations evaluating the mechanisms
by which RA therapies reduce vascular inflammation and its impact on articular disease
activity are warranted.


  1. Solomon DH, Giles JT, Liao KP, Ridker PM, Rist PM, Glynn RJ, et al. Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2023 Mar 1;82(3):324–30.
  2. Giles JT, Sattar N, Gabriel S, Ridker PM, Gay S, Warne C, et al. Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial. Arthritis & Rheumatology. 2020;72(1):31–40.