Disease-modifying antirheumatic drugs stop or slow the disease process in inflammatory forms of arthritis. 

DMARDs help preserve joints by blocking inflammation. Without DMARDs, inflammation would slowly destroy your joint tissues over the years. 

Each DMARD works differently. Conventional DMARDs restrict your immune system broadly. Targeted DMARDs block precise pathways inside immune cells. Biologic DMARDs are produced by living cells and work on individual immune proteins called cytokines. 
DMARD Combination Therapies

DMARD Combination Therapies

Sometimes a single medication is all that’s needed to control inflammatory arthritis. But more commonly, two or more medications used together – combination therapy – is required to relieve symptoms and prevent long-term joint damage and disability.

Double Therapy

Methotrexate is often used in combination with other DMARDs. Conventional DMARDs that have been paired with methotrexate include sulfasalazine, hydroxychloroquine, cyclosporine, leflunomide and azathioprine. Although studies of these combinations have shown differing levels of benefit, the combinations of methotrexate plus leflunomide and methotrexate plus sulfasalazine are among the most effective. 

DMARD Plus a Biologic

In many cases the effectiveness of biologics is improved by adding a DMARD, most commonly methotrexate.

Triple Therapy

If one or two medications are not enough, doctors can turn to triple therapy. The most common combination is methotrexate, sulfasalazine and hydroxychloroquine. Research shows that in some cases, using three conventional DMARDs together is just as effective as using a DMARD in combination with a biologic drug.

DMARDs and Anti-inflammatories

DMARDs are often prescribed with other medications – such as corticosteroids or NSAIDs -- for quick relief of inflammation and pain. This is particularly important during the time it takes DMARDs to take effect, which can be several weeks or months.
Because DMARDs suppress your immune system to control inflammation, all of them will increase your risk of infection. If you have signs of infection – chills, fever, sore throat or 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. Discuss your family plans with your doctor before taking any medication.

Each DMARD has different specific benefits and risks. Be sure to talk over any concerns with your doctor.

The list below contains both conventional and targeted DMARDs.
Benefits and Risks


Benefits: Apremilast is used in adults with psoriatic arthritis. It may be just as effective alone as it is in combination with other 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 suppresses the immune system to treat inflammation in autoimmune conditions including dermatomyositis, lupus, inflammatory bowel disease and vasculitis. It is sometimes used to treat rheumatoid arthritis. 

Risks: The most common side effects of azathioprine are nausea, vomiting and diarrhea. Liver and pancreas damage are less common, but can occur.


Benefits: This drug is for adults with moderate to severe rheumatoid arthritis whose disease has not responded to a TNF inhibitor. It may be used alone or in combination with other non-biologic DMARDs.

Risks: Serious infections, cancers, and blood clots have happened in people taking this drug.


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 inflammation, 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 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 drugs. 

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 a potent suppressor of the immune system. It’s used for people with rheumatoid arthritis or vasculitis, or for people with lupus who have kidney disease.

Risks: Some of the most common side effects of mycophenolate mofetil are nausea and diarrhea. Taking antacids may decrease its effectiveness. Women of childbearing age should use an effective form of birth control at least four weeks before, during and six 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.


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.
Taking DMARDs for your inflammatory arthritis will decrease pain and inflammation, prevent joint damage, and slow the progression of your disease. They also may bring side effects, some troublesome, others more serious.

To spot the most serious side effects, your doctors will monitor you with regular lab tests.

Most important, you need to inform your doctor immediately if you experience any side effect, especially nausea, vomiting, fever, rash, or symptoms of infection. Call your doctor if you think you’re pregnant or if you’re planning on becoming pregnant.
Side Effects and Solutions

Injection Site Reactions

For most people, the benefit of taking an approved drug outweighs its possible side effects. 

Although side effects can develop within the first six to nine months of treatment, the risk declines with continued use, especially if the drug is improving your condition. 

Injection Site Reactions 

Injection site reactions are fairly common, especially at the beginning of your treatment. Injection site reactions include 

  • Redness. 

  • Swelling. 

  • Itching. 

  • Pain. 

Most reactions clear up without treatment, but you can use a cold compress, topical corticosteroids, oral antihistamines or acetaminophen to ease discomfort. If symptoms persist past 5 days or get worse, call your doctor. You should also change the spot where you inject yourself each time.  

Infusion Reaction

If your biologic is given as an infusion, the clinic or facility will begin by getting your vital signs – temperature, blood pressure and pulse. A health professional will continue to monitor you during and after the infusion until you leave the facility. 

Before your scheduled biologic infusion, you may receive “pre-meds,” such as an antihistamine, antiemetic (for nausea) or an anti-inflammatory drug (NSAID). These will prevent any mild reactions, such as  

  • Pain. 

  • Swelling. 

  • Redness at infusion site. 

  • Headache. 

  • Flushing. 

  • Nausea. 

  • Rash.  

If any of the following more serious reactions occur, the infusion can be stopped and the reaction will be treated on site: 

  • Difficulty breathing. 

  • Chest pain or tightness. 

  • High or low blood pressure. 

  • Swelling of face and hands. 

  • Fever. 

  • Chills. 

  • Anaphylaxis. 


Because biologic therapies suppress the immune system, treatment leaves you more prone to infection. The most common are colds, upper respiratory tract infection, sinus infection, sore throat, bronchitis or urinary tract infections. 

Tips for avoiding infections: 

  • Wash hand frequently. 

  • Avoid crowded areas, enclosed spaces, public transportation and childcare facilities. 

  • Tell friends and family not to visit if they are sick. 

  • Talk to your doctor before scheduling vaccinations, dental appointments or manicures. 

  • Do not share cups, utensils or personal items. 

  • Do not swim in lakes, rivers, ponds or public pools. Avoid hot tubs. 

  • Ask your doctor about contact with your pets. It’s probably a good idea not to change cat litter or to clean up after the dog. Birds, fish, rodents, reptiles and farm animals should be avoided. 

  • Check with your doctor about whether it’s safe to work in the garden with soil or mulch. 

  • Avoid unpasteurized food, raw eggs or fish, soft cheeses and shellfish. 


Headaches occur more commonly in patients taking biologics than the general public. Try placing a cold pack on your forehead for 10–15 minutes. Or you can try lying down in a dim room for a few minutes, taking a warm shower, or massaging your head and neck. Avoid looking at a computer or smartphone screen for extended periods. It might also help to reduce the amount of caffeine you consume. 


There are a number of non-drug remedies you can try to combat queasiness. 

  • Place a cold compress on your forehead. 

  • Lie down in a dark, quiet room. 

  • Avoid heat, humidity and stuffy rooms. 

  • Breathe fresh air deeply through your nose; sometimes inhaling peppermint or drinking ginger tea helps. 

  • Suck on ice or sip cool water. Nibble on a saltine cracker if you think your stomach can handle it. Avoid sugary drinks or snacks. 

Recognize New Symptoms

A key piece of advice is to listen to your body. The following symptoms are signs of an infection or a more serious condition and you should contact your doctor right away: 

  • Fever, sweat or chills. 

  • Cough. 

  • Muscle aches, weakness/numbness or tingling. 

  • Shortness of breath or chest pain. 

  • Rash or painful sores; warm, red or painful skin. 

  • Diarrhea or stomach pain. 

  • Burning during urination or urinating more than normal. 

  • Unusual fatigue. 

  • Vision problems or dizziness. 

  • Poor appetite or weight loss. 

  • Bleeding or bruising easily. 

DMARDs must be taken safely and with certain precautions.

Before you start taking a DMARD, your doctor will take a baseline x-ray and blood tests. Your disease and any potential drug side effects will be monitored over time. Some of the medications can cause liver damage so you’ll need to let your doctor know if you drink alcohol regularly. You’ll also need to discuss  vaccinations and any pregnancy plans with your doctor before staring on DMARDs.

Safety topics for you to discuss with your doctor include:
Safe Use

Preexisting Medical Conditions

Medical conditions you have before you start a DMARD may increase your risk of side effects. Let your doctor know if you have an active infection, kidney or liver disease, cardiovascular disease or a history of cancer. Also, let your doctor know if you have allergies to other drugs.

Other Medicines You Take

Let your doctor know all of the drugs and supplements you take. Drugs can interact with one another. Some drugs may interfere with the effectiveness of your DMARD, while others may increase your risk of side effects. 

How to Take the Medicine

DMARDs can be given in different ways (oral or injected), on different schedules (daily, weekly) and in many different amounts. Be sure you understand exactly how much you need to take and how often. Never increase your dose unless your doctor advises. 

Some medicines can cause stomach upset if taken on an empty stomach. Others work best on an empty stomach. So be sure to take the medicine as directed.


Your doctor may recommend you have periodic checkups or lab tests. These appointments will  determine if the drugs are working for your arthritis and if they may be affecting your blood, internal organs or eyes. These tests can help your doctor decide if you need a change in dose or a different medication.


Because DMARDs suppress the immune system, you are susceptible to infections. Let your doctor know if you are on a DMARD and scheduling a surgical or dental procedure. Get all the immunizations recommended by your doctor. If you notice signs of infection let your doctor know right away.

Side Effects

Speak with your doctor about side effects to watch for and what to do if you experience them. 

Food and Supplements

Ask your doctor about particular foods or supplements you should or should not take while taking a DMARD. Taking a folic acid supplement with methotrexate, for example, can reduce the drug’s side effects.  Cyclosporine should not be taken with grapefruit juice.


DMARDs and alcohol don’t always mix. Methotrexate, leflunomide and cyclosporine can affect the liver. Drinking alcohol while taking those drugs can increase the risk of liver damage.

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