Features August 2018 Issue

Long-Term Benefits of RA Drugs

Several biologic drugs for rheumatoid arthritis have been around long enough to learn about potential long-term effects.

The number of drugs to treat rheumatoid arthritis (RA) has been expanding since the 1980s, when the drug methotrexate began being used. The drugs target the underlying cause of the disease. RA is an autoimmune disease, in which the body’s immune system misfires and attacks joints, causing a chronic inflammatory response.

Methotrexate interrupts the inflammatory process. Newer drugs developed over the last 20 years more precisely target the cells and chemicals (called cytokines) that produce inflammation. These are called biologic disease-modifying antirheumatic drugs (bDMARDs).

“These drugs reduce joint swelling and pain and improve function,” says Cleveland Clinic rheumatologist M. Elaine Husni, MD, MPH. But do bDMARDs have benefits beyond this? The answers are beginning to come in. In particular, studies are showing a reduction in the need for joint replacement surgeries and a potential benefit for the heart.

WalkingCouple

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Use of biologic DMARDs coincides with a decrease in joint replacement surgeries.

Promises with Caveats

These are encouraging findings, but Dr. Husni offers a few words of caution. First, there are at least 10 bDMARDs. (More are in development.) They work by different mechanisms and have different side effects. The diversity means there are more options to individualize treatment. But when assessing long-term benefits, they aren’t necessarily equal. Certain bDMARDs may be more or less beneficial depending on how RA affects each person.

Another limitation relates to the types of studies used to measure long-term effects. The ideal study is a randomized, controlled clinical trial. With this study design, one group of people who take the medication would be compared to a control group that does not. This can’t be done over long periods of time because it would be unethical to withhold medication. Therefore, evidence comes from observational studies, which do not have a controlgroup.

Fewer Joint Replacements

Even with those caveats, there appear to be positive long-term effects of reducing inflammation. “Use of bDMARDs has allowed us to halt or slow down progression of RA, meaning fewer people may need joint replacements,” says Dr. Husni. The number of hip and knee joint replacements has been rising among people with osteoarthritis, but it has decreased among people with RA.

Different studies have come to somewhat different conclusions. For example, a study published in The American Journal of Pharmacy Benefits (December 2014) found that after the introduction of three bDMARDs (in 1998, 1999 and 2002) there was a 32 percent reduction in knee replacements and 24 percent reduction in hip replacements among people with RA. Another study found a reduction in knee replacements, but not hipreplacements.

Heart Health

Researchers are also looking into whether bDMARDS might help the heart. This is important because people with RA have up to twice the risk for heart disease as people without it. The reason for this is not known, but inflammation may have a role.

The buildup of plaque in the arteries (atherosclerosis), which can lead to a heart attack, is an inflammatory process. It’s thought that the chronic inflammation that occurs with RA may contribute to this.

“The proposed mechanism for reducing heart disease is lowering the burden of chronic inflammation over time,” says Dr. Husni. Several studies suggest favorable effects on the heart with some bDMARDs.

A study now underway is using high-tech imaging studies to determine whether certain bDMARDs reduce inflammation in the heart. Results are expected in 2022.

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