Severe and advancing cases of rheumatoid arthritis (RA) are typically treated with disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs).

RA is an autoimmune disease. This means it causes the immune system to attack parts of its own body. For people with RA, the immune system attacks the lining of the joints, usually in the hands and feet. Symptoms of RA include stiff, swollen, and painful joints.

RA is a progressive disease. It can worsen and spread to other areas of the body, including other joints and major organs. There’s no cure at the moment, but there are several effective treatment options to manage symptoms.

The primary treatment options for severe and advancing RA are DMARDs and NSAIDs.

These drugs can help alter how the immune system works, which results in reduced inflammation. Unlike DMARDs, NSAIDs don’t change the course of the disease. They don’t prevent joint damage either.

DMARDs work by suppressing the immune response, which helps reduce inflammation. Because of the way they alter the course of RA, they help prevent permanent joint damage and other complications.

DMARDs are usually the first-line treatment for RA, in combination with an NSAID or low doses of a steroid. DMARDs are effective in slowing the progression of the disease, so doctors often prescribe them as soon as a diagnosis is made. Sometimes you may even start one before an RA diagnosis is confirmed.

Although DMARDs are very useful, it can take several weeks or even months before they begin to take effect. Hence, doctors also start them with an NSAID or a steroid for symptom relief.

Several drugs make up this class. Each has its own level of effectiveness and side effects. Figuring out which DMARD is the most effective for your RA may end up being a case of trial and error.

Traditional DMARDs, sometimes known as nonbiologics, affect the whole immune system. In comparison, biologics target specific proteins that affect the immune response.

Traditional DMARDs are often administered orally. They include:

  • cyclosporine (Neoral, Sandimmune)
  • hydroxychloroquine (Plaquenil)
  • leflunomide (Arava)
  • methotrexate (Otrexup, Rasuvo), the most commonly prescribed RA drug
  • sulfasalazine (Azulfidine)

JAK inhibitors are the newest type of DMARD for RA. These synthetic drugs target certain inflammatory pathways.

JAK inhibitors are administered orally. They include:

  • baricitinib (Olumiant)
  • tofacitinib (Xeljanz)
  • upadacitinib (Rinvoq)

Biologics are complex medications. They’re created through a biological process instead of being synthetically created using chemicals. Biologics may be made using cell cultures or derived from other natural sources, such as microorganisms or animal cells.

One type of biologic is genetically engineered to block a cytokine, a kind of messenger protein that tells the immune system to react. Another type targets tumor necrosis factor (TNF), a protein that increases inflammation.

Generally, doctors only recommend biologics for cases of RA that haven’t responded well to DMARDs, or for people who can’t take traditional DMARDs. In some cases, biologics and traditional DMARDs are given in combination, often along with NSAIDs.

Biologics are administered via injection or infusion, typically over a period of several hours.

Biologics might seem less convenient than other DMARDs because some have to be administered in a medical setting. They might become more convenient over time, as doses are usually given only once a month.

Currently available biologics include:

  • abatacept (Orencia)
  • adalimumab (Humira)
  • anakinra (Kineret)
  • certolizumab pegol (Cimzia)
  • etanercept (Enbrel)
  • golimumab (Simponi)
  • infliximab (Remicade)
  • rituximab (Rituxan)
  • tocilizumab (Actemra)

Biosimilars are structurally similar to biologics. They’re also available in some cases and typically less expensive.

A doctor may recommend you take NSAIDs along with your prescription treatments. NSAIDs include medications you probably have at home, such as:

  • aspirin
  • ibuprofen (Advil, Motrin)
  • naproxen (Aleve, Naprosyn)

NSAIDs work well for relieving acute pain and inflammation. But they don’t affect the progression of RA or prevent disease complications such as long-term joint damage.

DMARDs can have a variety of side effects, yet most people tolerate the drugs well.

Because of the way they suppress the immune system, taking them increases your risk of infections. Talk with your doctor about vaccinations you may need to prevent shingles, pneumonia, and other illnesses. Also, talk about a potential increase in your risk for COVID-19.

Each DMARD has different side effects, so you’ll want to discuss with your doctor the side effects of each drug they prescribe.

Common reactions to DMARDs include:

  • dizziness
  • upset stomach
  • rash
  • headache

Biologics will generally have the same side effects listed above, along with a few others, such as:

  • sore throat
  • wheezing
  • high blood pressure during the injection or infusion
  • skin reactions at the site of the injection or infusion
  • pain at the site of the injection or infusion

Because JAK inhibitors are newer than other treatment options, there’s less information available about their side effects. They can cause the typical side effects of DMARDs and more serious side effects. People who take JAK inhibitors have an increased risk of:

  • heart-related complications, including heart attack and stroke
  • blood clots

DMARDs (including JAK inhibitors) and biologics both increase your risk of cancer.

NSAIDs share some of the same side effects as DMARDs. However, they tend to result in milder side effects overall. Possible reactions include:

  • dizziness
  • upset stomach
  • headache
  • stomach ulcers
  • bleeding

Depending on your treatment, your doctor may want to monitor your:

  • liver and kidney function
  • blood pressure
  • cholesterol and other lipids
  • heart
  • lungs

The benefits of DMARDs and NSAIDs typically outweigh any risks. Most side effects can be treated or will subside on their own.

It’s very important that you do not stop taking your medication without talking with your doctor first. Make an appointment with them if you want to discuss any concerns about your treatment plan.