DMARDs: Benefits and Risks

Use this information to help discuss medication choices with your doctor.


Weighing the risks and the benefits for any prescription medicine can be challenging, especially if you’ll need to take the medication for a long time. Because inflammatory arthritis is a chronic condition, most people with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or juvenile idiopathic arthritis (JIA) will take disease-modifying antirheumatic drugs (DMARDs) for the long run.

There are three types of DMARDs: traditional, targeted and biologic. Each DMARD works differently on the immune system, but they all preserve joints by reducing chronic inflammation. The four most commonly used traditional DMARDs are hydroxychloroquine, sulfasalazine, leflunomide and methotrexate, with methotrexate being the most popular.

Because DMARDs suppress your immune system to stop rampant inflammation, all of them will increase your risk of infection. If you have signs of infection – chills, fever, sore throat, painful urination, for example – report them to your doctor immediately. They also make receiving live vaccines dangerous. Use extra care to avoid infection and discuss vaccines with your doctor. 

Several DMARDs can damage the fetus but others are safe during pregnancy. “I encourage discussing family planning prior to starting any oral DMARD,” says Gonzalez-Mayda, MD, assistant Professor of Medicine at Washington University School of Medicine, in St. Louis, Missouri.

DMARDs do not provide immediate relief. The drugs will take a couple of months to take effect, so your doctor may prescribe NSAIDs or a corticosteroid for pain relief in the meantime.

Although there are no cookie-cutter recipes for everyone with inflammatory arthritis, these are relatively safe medications. “Everyone is different,” says Dr. Gonzalez-Mayda. “I always want to emphasize to patients that we need to look at every scenario for each individual and ask what’s best for you.”

Each DMARD has different specific benefits and risks. This listing will give you an overview, but be sure to talk over any concerns with your doctor.

Traditional DMARDs


Benefits: This drug suppresses the immune system to treat inflammation in autoimmune conditions including dermatomyositis, lupus, inflammatory bowel disease and vasculitis. It also is sometimes used to treat rheumatoid arthritis, but not as often as methotrexate.
Risks: The most common side effects of azathioprine include nausea, vomiting and diarrhea. Liver and pancreas damage are less common, but can occur.


Benefits: Cyclophosphamide is reserved for severe rheumatoid arthritis that has not responded to other treatments. It also is used for complications of lupus, myositis, scleroderma or vasculitis.
Risks: Cyclophosphamide can have serious side effects, including reduced blood cell counts, fertility problems, birth defects, bladder trouble and heightened cancer risk. If you take this medicine, you will have to be carefully monitored by your doctor.


Benefits: Cyclosporine is a potent immunosuppressant drug that decreases the pain and inflammation of arthritis, prevents joint damage, and slows the progression of inflammatory arthritis over time.
Risks: Cyclosporine use requires frequent laboratory testing and has many drug interactions. The most common and serious side effects are high blood pressure and kidney problems.


Benefits: Hydroxychloroquine is a relatively safe medicine that is used to treat mild rheumatoid arthritis. It can be used in combination with other drugs to treat more severe cases. It is also used for complications of lupus.
Risks: Hydroxychloroquine has few side effects, but nausea and diarrhea may occur when you first start taking the drug. In very rare cases, vision loss has happened. You will have to see an eye doctor once a year for screening.


Benefits: Leflunomide is used to treat moderate to severe rheumatoid arthritis, often when methotrexate is not controlling symptoms. It is usually given alone, not in combination. Leflunomide is sometimes used to treat psoriatic arthritis.
Risks: This drug most commonly causes nausea and diarrhea. It can also cause hair loss. It clears from the body slowly; a wash-out procedure may be needed before trying to get pregnant.


Benefits: This is the most commonly prescribed drug for rheumatoid arthritis and one of the most effective for several kinds of inflammatory arthritis. Doctors often use methotrexate in combination with other DMARDs to treat arthritis.
Risks: Methotrexate most commonly causes nausea. Other common side effects include swollen gums,  mouth sores and excess tiredness. Women who want to become pregnant should not take methotrexate. Methotrexate can cause an increase in liver enzymes and is therefore not recommended for those who drink alcohol.

Mycophenolate mofetil

Benefits: This drug is used for people with rheumatoid arthritis or vasculitis, or for people with lupus who have kidney disease. It is a potent suppressor of the immune system.
Risks: Some of the most common side effects of mycophenolate mofetil are upset stomach, nausea and diarrhea. Taking antacids may decrease its effectiveness. Women of childbearing age should use an effective form of birth control at least 4 weeks before, during and 6 weeks after treatment.


Benefits: This drug is used for people with rheumatoid arthritis and other autoimmune conditions. Sulfasalazine can lessen pain and swelling and slow the progression of arthritis.
Risks: Sulfasalazine may cause nausea and vomiting. It can cause yellow-orange urine or skin. It is generally safe for pregnancy, but should not be taken while breastfeeding. This drug may lower sperm count in men, an effect that gets better once the drug is stopped.

Targeted DMARDs


Benefits: Apremilast is one of the newest treatments for adults with psoriatic arthritis. Clinical studies show the drug may be as effective alone as in combination therapy with DMARDs.
Risks: Nausea and diarrhea are common side effects. It has been associated with new or worsening depression, suicidal thoughts and other mood changes. Tell your doctor if you have unexplained weight loss.


Benefits: This drug is used for adults with moderate to severe rheumatoid arthritis whose disease has not responded to methotrexate. 
Risks: Your cholesterol levels will need to be monitored. The most common side effects are upper respiratory tract infections, diarrhea, headache, nasal congestion, sore throat and runny nose. This drug should also not be used if you have liver problems.

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