Treating Rheumatoid Arthritis With Disease-Modifying Therapies

Rheumatoid arthritis (RA) treatment has made major strides over the past few decades — first with the use of disease-modifying anti-rheumatic drugs (DMARDs), then with the introduction of biologic DMARDs and targeted synthetic DMARDS, also known as Janus kinase (JAK) inhibitors. Although each type of medication works in a different way, each option can help you gain and maintain control of your RA.

“When I started treating rheumatoid arthritis about 30 years ago, we were limited to relieving pain and swelling with nonsteroidal anti-inflammatory drugs (NSAIDS) and steroids," says Stuart Kaplan, MD, a partner with Rheumatology Consultants in Hewlett, New York. "Today, we can change the course of this disease with newer treatment options."

That said, it's important to understand the differences between these RA treatment options.

Traditional DMARDs

Traditional (or conventional) DMARDs are drugs that can help prevent joint damage and deformity from RA. They work by suppressing the immune system on a broad level.

“Methotrexate is the gold standard and is often prescribed to someone with rheumatoid arthritis who has active disease," Dr. Kaplan says. “And earlier treatment is best — once joint damage has occurred, it can’t be undone."

Other commonly used DMARDs for RA include hydroxychloroquine and sulfasalazine, which can be prescribed alone or with methotrexate. These drugs tend to be a little weaker, but they have fewer side effects, Kaplan says.

Biologics

Biologics are genetically engineered drugs that work in a more targeted way by blocking cytokines, the proteins needed to cause an immune response.

“Biologics are a godsend for people who need more than traditional DMARDs, but they come with bigger risks and a higher price," Kaplan says. However, he says, they're quite effective and should be used sooner rather than later if needed.

According to the most recent treatment guidelines from the American College of Rheumatology, approved biologics for RA include etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), golimumab (Simponi), certolizumab (Cimzia), abatacept (Orencia), tocilizumab (Actemra), sarilumab (Kevzara), and rituximab (Rituxan).

JAK Inhibitors

JAK inhibitors are oral DMARDs that can be used instead of biologics, explains Kaplan. They’re even more targeted than biologics, as they work inside immune cells to block communication, thus disrupting the response pathway that leads to inflammation in your joints. And some research has found that JAK inhibitors are just as — if not more effective than — biologics. JAK inhibitors approved for rheumatoid arthritis include: tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq). They can be costly, and the U.S. Food and Drug Administration (FDA) now requires a warning label that acknowledges an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with certain JAK inhibitors that treat inflammatory arthritis.

RELATED: The Consumer’s Guide to JAK Inhibitors for Rheumatoid Arthritis

A Side-by-Side Comparison of Disease-Modifying RA Medications

Key similarities and differences between these RA treatments include:

• Delivery Method Traditional DMARDs are usually taken in pill form, and methotrexate, the most common type, is usually given once a week. Biologics are typically injected under the skin — you can do this yourself at home — or given by intravenous infusion in a medical setting. Frequency and dosage varies from one biologic to another, notes CreakyJoints. Similar to DMARDs, JAK inhibitors are another oral medication option, but they’re usually taken once or twice a day.
• Drug Target Traditional DMARDs target the entire immune system, whereas biologics work by targeting specific steps in the inflammatory process, and JAK inhibitors block action in your body to help prevent the inflammation from even starting.
• Response Time It can take a month or more before you'll know whether a traditional DMARD or biologic is working for you, according to the Cleveland Clinic. With JAK inhibitors, you may experience results within two weeks. In the meantime, your doctor may also prescribe an NSAID or a steroid medication to help relieve joint pain and swelling.
• Risks One thing each of these medications have in common is that they can all increase your risk for infections, so you need to tell your doctor if you experience a fever, chills, or cold symptoms.
• Side Effects Each type of DMARD has its own set of side effects, so you should go over these with your doctor if a specific DMARD has been prescribed. For instance, methotrexate can cause liver damage and bone marrow suppression, per MedlinePlus. A common side effect from biologics is a skin reaction at the site of injection, according to the Cleveland Clinic. There are also other more serious side effects to evaluate before starting biologic treatment, including an increased risk for skin cancer, notes the Arthritis Foundation. As mentioned above, JAK inhibitors now carry a warning label for heart-related events but it’s important to discuss this with your rheumatologist and weigh the risks with the benefits.
• Cost Biologics and JAK inhibitors are much more expensive than traditional DMARDs. Be sure to check with your insurance company if you have any questions about your prescription coverage. If you need help paying for your RA treatment, you may be able to apply for assistance through your specific medication’s manufacturer.

RELATED: 8 Pros and Cons of Switching Rheumatoid Arthritis Medications

Treating RA With a Mix-and-Match Approach

Traditional DMARDs are often used in combination with each other. A traditional DMARD can also be paired with a biologic, but only one biologic is prescribed at a time. If biologics don’t help you achieve remission, your doctor may suggest trying a JAK inhibitor instead. If needed, a JAK inhibitor may also be used in combination with a traditional DMARD.

“Today, if methotrexate isn’t working, doctors are more likely to add on a biologic," Kaplan says. "In some cases, methotrexate may be stopped if the biologic is working well. If the first biologic isn’t working, your doctor may try switching you to a different type of biologic."

When to start a traditional DMARD, add another, move to a biologic, or try a JAK inhibitor are decisions that you'll make together with your doctor. No matter what medication you’re taking, it’s important to discuss potential side effects and risks. You may also need regular blood tests to make sure you're not in danger from certain side effects.

Additional reporting by Erica Patino and Kerry Weiss.