A recent study has shown that the use of a combination of a tumor necrosis factor (TNF) inhibitor along with methotrexate therapy in people with rheumatoid arthritis (RA) was associated with a reduction in heart attack risk of 80 percent compared with patients using methotrexate alone, according to research presented recently at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.



Rheumatoid arthritis is a chronic, systemic, autoimmune disease that not only causes pain, stiffness, swelling, and limitation of function in joints, but also damages internal organs as well.

Approximately, 2.1 million Americans are afflicted with RA, most of them women. As mentioned above, while joints are the principal areas affected by RA, inflammation can develop in other organs as well. Heart attacks, resulting from inflammation of the coronary vessels, are more common in RA sufferers.

Researchers recently studied the risk of heart attack in patients using a TNF-inhibitor (a drug that blocks cytokines and can turn off the chronic inflammation that causes destruction in RA), methotrexate (a drug used to treat RA by blocking the metabolism of cells) and other disease modifying anti-rheumatic drugs (DMARDs), which are a category of drugs used in RA to slow down the disease progression, in a large population of patients with RA—many of whom were also taking aspirin.

Using information obtained from MediCal, California's Medicaid program, researchers studied patients over the age of 18, suffering from RA, who were treated with TNF-inhibitors, methotrexate, or other DMARDs, over a six-and-a-half year period.

A total of 19,233 patients with RA were identified. The patients' mean age was 55 years.

Approximately 79 percent were women. Of these patients, 13,383 took methotrexate; 14,958 took other DMARDS; and 4,943 took TNF-inhibitors. Exposure of one group of patients to TNF-inhibitors (taken alone or in combination with methotrexate) was compared to that of the other group taking methotrexate alone.

During the study period, 441 patients suffered heart attacks, of which eight percent were fatal.

Researchers found that patients on a combination of TNF-inhibitors with methotrexate treatment had a heart attack risk of only 20 percent of the risk compared to patients taking methotrexate alone.

However, there was no statistical difference seen among patients who were taking TNF-inhibitors alone, TNF-inhibitors with other DMARDs, other DMARD therapies without methotrexate, or a combination of DMARDs and methotrexate. Therefore, this reduction in cardiovascular events appears to be a function of the combination of methotrexate and TNF-inhibitors.

“TNF-inhibitor therapy, in combination with methotrexate, dramatically reduces the risk of heart attacks in patients with RA and should be seriously considered— especially in high-risk patients,” said Gurkirpal Singh, MD, clinical professor of medicine in the division of gastroenterology at Stanford University School of Medicine, and an investigator in the study.

The notion that RA is a potentially crippling disorder is widely accepted. However, what is not generally known is that it is a potentially lethal disease leading to an increased risk of heart attack and stroke.

It is imperative that patients with RA understand the systemic nature of this condition and the need for aggressive intervention. This study lends more ammunition to the argument that patients with RA need to be treated with a combination of methotrexate and biologic therapy to not only reduce the chances for crippling deformity but also to reduce the likelihood of cardiovascular death.