Immunomodulators Reduce Vascular Inflammation, Cardiovascular Risk in Patients With RA

Addition of immunomodulators, including TNF inhibitors, to standard therapy resulted in improvements in vascular inflammation among patients with RA.

Immunomodulators reduce vascular inflammation and risk for cardiovascular (CV) events in patients with moderately active rheumatoid arthritis (RA), according to study findings published in Annals of the Rheumatic Diseases.

Recent randomized clinical trials have shown that immunomodulators reduce incidence of CV events in the general population, which led to whether the addition of immunomodulators to low-dose methotrexate (MTX) reduced CV events in patients with RA who demonstrate a greater risk for CV events compared with the general population.

Researchers conducted a multicenter, randomized, active, comparator trial across 41 centers in the US between March 2016 and November 2021 to assess whether immunomodulators reduced CV events in RA.

During the follow-up, patients underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans to assess the primary outcome (change in target-to-background ratio [TBR]), which is predictive of atherosclerotic disease events.

Future studies will explore the mechanisms by which RA therapies appear to ameliorate vascular inflammation independent of their effect on articular disease activity.

The researchers compared the addition of tumor necrosis factor (TNF) inhibitors to low-dose MTX vs triple therapy, which included the addition of hydroxychloroquine and sulfasalazine to low-dose MTX.

Of a total of 159 patients, 138 completed the follow-up and 115 received FDG-PET/CT scans. Among the 115 patients (median age, 58 years; 71% women), 58 received dual treatment with TNF inhibitors and MTX, while 57 received triple therapy.

After 24 weeks of treatment, both the treatment groups demonstrated significantly reduced TBR on FDG-PET/CT scans compared with baseline scans (change in the TNFi group, -0.24; P =.001 and change in the triple therapy group, -0.19; P =.001). However, the difference between the 2 treatment groups did not reach statistical significance (difference in changes, -0.02; 95% CI, -0.19 to 0.15; P =.79).

Both immunomodulatory treatment strategies effectively reduced arterial tissue inflammation due to atherosclerosis, as seen by decreased TBR on FDG-PET/CT scans, thus lowering risk for CV events.

Study limitations included the lack of patient and clinician blinding, poor adherence to the randomly assigned treatment, need for modifications to treatment protocols due to the COVID-19 pandemic, short follow-up duration, small sample size requiring re-estimation, and lack of using actual incidence of CV events as the primary outcome.

“Future studies will explore the mechanisms by which RA therapies appear to ameliorate vascular inflammation independent of their effect on articular disease activity,” the study authors said.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original article for full list of disclosures.


Solomon DH, Giles JT, Liao KP, et al. Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. Published online November 30, 2022. doi:10.1136/ard-2022-223302