Biologics that Treat Arthritis May Lower Cardiovascular Risk

Biologic drugs may reduce cardiovascular risk in patients with rheumatoid arthritis by altering the effect of inflammation, according to a study published in August 2024 in RMD Open.

George Athanasios Karpouzas, M.D.

In a study, researchers, led by George Athanasios Karpouzas, M.D., an investigator at The Lundquist Institute, Torrance, Calif., and professor of Medicine at David Geffen School of Medicine at UCLA, wanted to explore whether biologic drugs used to treat patients with arthritis influence the inflammatory markers on long-term cardiovascular risk.

Biologic disease-modifying antirheumatic drugs (bDMARDs) are a class of therapeutics that treat several inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. These biologics include infliximab (Remicade and its biosimilars), adalimumab (Humira and its biosimilars), etanercept (Enbrel and its biosimilars), rituximab (Rituxan and its biosimilars), abatacept (Orencia) and tocilizumab (Actemra and its biosimilars).

Researchers studied 4,370 participants without cardiovascular disease in an observational cohort of patients with rheumatoid arthritis. The first endpoints was the development major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death. The second was the development any ischemic cardiovascular events (iCVE) including MACE plus revascularization, angina, transient ischemic attack and peripheral arterial disease.

Patients were seen at 13 centers across 10 countries (Canada, Greece, Mexico, Netherlands, Norway, South Africa, Spain, Sweden, UK and USA) and were followed prospectively or via retrospective chart review. Patients were mostly middle-aged women with seropositive and moderately-to-severely active disease.

A quarter of the patients used corticosteroids at baseline, one-third received methotrexate and 12% used biologics. Of 4,370 patients, 515 (11.8%) used biological disease-modifying antirheumatic drugs at baseline.

Data were collected for C-reactive protein and 28-joint Disease Activity Score based on C-reactive protein. The 28-joint Disease Activity Score is used to evaluate disease activity and treatment response in rheumatoid arthritis. C-reactive protein a protein made by the liver that increases when there is inflammation in the body. In this study, C-reactive protein was used as an inflammatory biomarker.

Researchers found that among patients taking biologics, there were 239 major adverse cardiovascular events and 362 ischemic cardiovascular events.

They found that clinical disease activity measured on the 28-joint Disease Activity Score was associated with both risk of major adverse cardiovascular events and ischemic cardiovascular events, whereas C-reactive protein was associated only with the risk of major adverse cardiovascular events.

The interaction of c-reactive protein and MACE was significant, researchers said. This, the authors said, suggests that biologics have an effect on the arterial wall inflammation and plaque composition, which offsets the influence of joint-derived inflammation.

One limitation is that patients in this study were seen at centers with an interest in rheumatoid arthritis-associated cardiovascular disease, which researchers said may introduce referral bias. Additionally, some centers evaluated patients prospectively while others conducted a retrospective chart review. Information on cardiovascular risk factors, disease characteristics and treatments were only available at baseline.