Treating Rheumatoid Arthritis With Disease-Modifying Therapies

Find out how traditional DMARDs, biologics, and JAK inhibitors stack up against each other.

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syringe injection with pills
The right treatment combination can help control your symptoms and prevent disease progression.iStock

Rheumatoid arthritis (RA) treatment has made major strides over the past few decades — first with the use of disease-modifying anti-rheumatic drugs (DMARDs) in the 1980s, then with the introduction of biologics in the late 1990s, and even more recently in 2012 with a class of drugs called 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 non-steroidal anti-inflammatory drugs (NSAIDs) and steroids," says Stuart Kaplan, MD, chief of rheumatology at Mount Sinai South Nassau hospital in Oceanside, New York, and a partner in Rheumatology Consultants, LLP. "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 DMARDs are drugs that can help prevent joint damage and deformity from RA. More than a dozen options exist, and they all 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 are genetically engineered drugs that work in a more targeted way by blocking cytokines, the proteins needed to cause an immune response. The first biologic medication for RA was introduced in 1998. Today, many biologics have been approved for treating RA.

“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.

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. Today, there are three types of JAK inhibitors available, though they also come with certain health risks and can be costly.

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 or given by intravenous infusion, a process that takes a few hours in a medical setting. Frequency varies from one biologic to another and can range from daily to every few months. 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 months before you'll know whether a traditional DMARD is working for you. With biologics, you're likely to experience results within four to six weeks, after just a few treatments. In the meantime, your doctor may also prescribe an NSAID or a steroid medication to help relieve joint pain and swelling. Meanwhile, JAK inhibitors can start working within days to a few weeks.
  • 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, bone marrow suppression, and miscarriage or birth defects. The most common side effect from biologics is a skin reaction at the site of injection, affecting up to 30 percent of people who take them. There are also other more serious side effects to evaluate before starting biologic treatment, including an increased risk for skin cancer. Serious side effects aren’t all that common with JAK inhibitors, though your doctor may monitor your lab work for abnormal results.
  • 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.

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.

Regardless, these medications are changing the way doctors think about treating RA.

“Years ago, I would’ve said it’s better to have osteoarthritis than rheumatoid arthritis," Kaplan says. "Today, I can say that there are actually better treatment options for RA."

Additional reporting by Erica Patino and Kerry Weiss


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