Combination Therapy for Rheumatoid Arthritis

Medically Reviewed by Neha Pathak, MD on January 25, 2022
3 min read

Treatments for rheumatoid arthritis (RA) curb inflammation in your body, protect your joints from damage, and ease symptoms like pain and stiffness. But sometimes one drug isn't enough to keep RA under control. That's where combination therapy comes in.

When you're diagnosed with RA, your doctor might start you on a disease-modifying antirheumatic drug (DMARD) called methotrexate. It's the medicine doctors prescribe first for most people with RA because it works so well.

Besides methotrexate, common DMARDs include hydroxychloroquine (Plaquenil), leflunomide (Arava), and sulfasalazine (Azulfidine).

If methotrexate doesn't improve your symptoms, it could be time to add one or more other medicines into the mix.

A few other drugs treat RA, and they work in different ways. Combining these medicines may be more likely to ease your symptoms and put you into remission than one drug alone.

In addition to DMARDs, the main types of RA drugs that can be combined in different ways are:

Biologics. These medicines are a newer type of DMARD. They're a manufactured version of natural proteins that curb inflammation.

This newer class of DMARDs includes abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), baricitinib (Olumiant), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), sarilumab (Kevzara), tocilizumab (Actemra), and tofacitinib (Xeljanz).

Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs, such as ibuprofen and naproxen, lessen pain and inflammation.

Corticosteroids, or steroids. They curb the immune system response to bring down inflammation in your body.

The combination of medicines your doctor prescribes depends on how long you've had RA and how severe your symptoms are.

Some common RA drug combinations are:

Double therapy. This treatment combines methotrexate with another DMARD, such as azathioprine (Azasan), cyclosporine, hydroxychloroquine, leflunomide, or sulfasalazine. Methotrexate plus leflunomide or methotrexate plus sulfasalazine seem to be the most effective two-drug combinations of conventional DMARDs. Another version of this treatment combines two or more biologic drugs.

DMARD plus a biologic. This combination therapy adds a biologic drug to methotrexate. "Biologic" DMARDs are usually most effective when paired with a "nonbiologic" DMARD, such as methotrexate.

Triple therapy. If two drugs don't relieve your symptoms, you can move up to triple therapy with three medicines. The most common triple therapy is methotrexate, sulfasalazine, and hydroxychloroquine.

DMARD plus an anti-inflammatory drug. Because DMARDs can take a few weeks or months to start working, your doctor might put you on an anti-inflammatory drug such as a steroid or NSAID for a short period of time. These drugs work quickly to lessen inflammation in your body. They can help with symptoms until your DMARD starts to work.

Everyone responds to these drugs a little differently. Your doctor will tailor a combination therapy to fit your RA. And if the first combination you try doesn't work, you can switch to something else.

Each of these medicines works in a slightly different way, and their effects can add up. Getting on the right combination of drugs could mean less joint pain, stiffness, and swelling. Combination treatment can also help slow damage to your joints.

There's some evidence that people with RA respond better to a combination of drugs than to one drug. Taking two or more medicines might improve your symptoms more than taking one medicine.

Each of the medicines that treat RA can cause side effects. Because DMARDs tamp down your immune system to ease inflammation, they can raise your risk for infections.

Other side effects from DMARDs are:

  • Nausea and vomiting
  • Diarrhea
  • Mouth sores and swollen gums
  • Liver or kidney problems
  • Trouble getting pregnant
  • Birth defects in the baby of a mother who took these medicines

Steroids can cause:

  • Weight gain
  • Weak bones
  • High blood pressure
  • Blood sugar changes

Taking two or more drugs together doesn't seem to cause more side effects than taking one drug alone. Just in case, your doctor will monitor you for any problems. You may need regular blood tests to make sure the medicine isn't harming your liver or other organs.

Before you start on any combination therapy, ask your doctor about the pros and cons. And let your doctor know if you develop any side effects while you're on the treatment.