Facts About DMARDs

Disease-Modifying Anti-Rheumatic Drugs

Medications categorized as disease-modifying antirheumatic drugs (DMARDs) are prescribed for treating rheumatoid arthritis (RA) and other autoimmune/inflammatory conditions, including ankylosing spondylitis, psoriatic arthritis, and lupus.

DMARDs are often referred to as immunosuppressants or immunomodulators because they appear to decrease inflammation by modifying the way your immune system works. This action helps slow down disease progression and alleviate symptoms.

The earliest DMARDs have been around for decades, so healthcare providers have a wealth of data to guide their treatment decisions. The medical community considers DMARDs to be highly effective long-term treatments. Most DMARDs take about three to six months to work, so you may not notice the benefits until you have been taking them for months.

DMARDs currently used for RA and similar conditions include:

  • Arava (leflunomide)
  • Azulfidine (sulfasalazine)
  • CellCept (mycophenolate mofetil)
  • Cuprimine (penicillamine)
  • Cytoxan (cyclophosphamide)
  • Imuran (azathioprine)
  • Neoral/Gengraf (cyclosporine)
  • Otezla (apremilast)
  • Plaquenil (hydroxychloroquine)
  • Rheumatrex/Trexall (methotrexate)

If a DMARD isn't having sufficient effects, you may be prescribed two or more to take together. DMARDs are often prescribed with drugs from other classes as well.

While DMARDs do carry some risk of serious side effects, laboratory monitoring can help identify problems early.

Taking pill from pillbox
Stephanie Deissner/F1online/Getty Images

This overview touches on some key information about each of these drugs. Speak to your healthcare provider about all possible side effects. Be detailed when sharing your medical and treatment history, including what medications you are currently taking, medications you're recently taken and side effects, your medical conditions, symptoms, and any drug allergies you have.

Arava (leflunomide)

Arava was first approved by the U.S. Food and Drug Administration (FDA) in 1998. It comes in tablet form and is taken orally.


Arava is only approved for treating active RA in adults. It's sometimes used off-label for managing psoriatic arthritis and psoriasis.

Special Considerations

  • This drug hasn't been evaluated for children under 12.
  • Arava is not safe for pregnant women.
  • If you're breastfeeding, you need to stop before you start taking Arava.
  • You shouldn't take this drug if you're currently taking the drug teriflunomide.
  • Arava has two black box warnings from the FDA: one related to embryo-fetal toxicity, the other related to severe liver injury or liver failure.

Azulfidine (sulfasalazine)

Usually called by its generic name, sulfasalazine is a combination of salicylate and an antibiotic. This oral medication has been around since the 1940s and is available in tablet form.


Sulfasalazine is approved to treat mild-to-moderate ulcerative colitis (UC), as a first-line or combination treatment, and to prolong the period of remission between UC attacks. It can be used for adults and for children age 6 and over.

It's sometimes used to treat RA but has become less popular over time due to the risk of side effects and the availability of other treatment options. This medication is also rarely used for the treatment of psoriatic arthritis, Crohn's disease, IBD-associated arthritis, and juvenile idiopathic arthritis (JIA).

Special Considerations

  • This drug should be avoided by people with allergies to sulfa drugs and/or aspirin and other salicylates.
  • Some recommendations state that, during pregnancy, sulfasalazine is an acceptable alternative to methotrexate or leflunomide, which both are known to cause fetal harm. However, sulfasalazine is not well studied during pregnancy and the potential long-term effects on a child exposed in utero are unknown.
  • Nursing mothers are advised not to take this drug, as it is believed to pass into breastmilk and may have the potential to cause brain damage in the baby.

CellCept (mycophenolate mofetil)

CellCept, an oral medication, has been on the market since 1995. It's an especially potent immunosuppressant.


This medication is FDA-approved to prevent organ rejection in kidney, heart, and liver transplants in adults, and kidney transplants in children. For its approved purposes, it's expected to be used alongside other immunosuppressants.

CellCept is sometimes used off-label for the treatment of RA, or for treatment of lupus with kidney disease, and vasculitis, as well as interstitial lung disease associated with autoimmune disorders, including RA and Sjogren's syndrome

Special Considerations

  • CellCept comes with a black box warning because it can increase the risk of fetal malformations and pregnancy loss in the first trimester.
  • This drug can affect sperm, increasing the risk of fetal toxicity.
  • This drug may reduce the effectiveness of birth control pills.
  • A second black box warning relates to an increased risk of lymphoma and other malignancies, particularly skin cancer.
  • A third black box warning was issued because CellCept use can lead to serious bacterial, viral, fungal, and protozoal infections—including viral reactivation of hepatitis B and C—which can lead to hospitalizations and death.

Cuprimine/Depen (penicillamine)

Penicillamine is a distant relative of penicillin that became available in the 1970s. It's associated with a high incidence of severe side effects, including some that can be fatal. You'll need close monitoring by your healthcare provider if you take this drug.


This drug is FDA approved for treating:

  • Severe, active RA that hasn't improved with other therapies
  • A genetic liver disorder called Wilson's disease
  • A genetic disorder that causes cystine stones in the urinary tract

This DMARD is not commonly used and it isn't a first-line treatment due to its risk of severe side effects. In fact, if you've been on 1,000 milligrams (mg) or more of penicillamine per day for a few months without improvement, your healthcare provider will likely recommend discontinuing it.

Special Considerations

  • You should not take penicillamine if you are breastfeeding, have kidney disease, or you've had severe side effects from penicillamine in the past.
  • If you're allergic to penicillin, there's a possibility you could also be allergic to penicillamine.
  • This medication increases your risk of developing diseases of the immune system, including systemic lupus erythematosus (SLE), polymyositis, myasthenia gravis, and Goodpasture syndrome.
  • Some side effects can be signs of a serious health problem, including anemia, low blood platelets (thrombocytopenia), low white blood cells (neutropenia), or serious kidney disease.

Imuran (azathioprine)

Imuran has been on the U.S. market since 1968. It is available in tablet form.


This drug is FDA approved for treating active RA and to prevent rejection in kidney transplants. It's sometimes used off-label to treat other autoimmune conditions, including dermatomyositis, systemic lupus erythematous (SLE), inflammatory bowel disease, and vasculitis.

Special Considerations

  • Imuran has a black box warning because the drug may increase your risk of cancer, including lymphoma. Malignancies have primarily been observed in people who've had transplants or are being treated for inflammatory bowel disease.
  • This drug is known to cause fetal harm and should be avoided during pregnancy whenever possible.
  • Imuran may temporarily lower sperm count and impair male fertility. Its impact on sperm may also cause birth defects.
  • Reliable contraception should be used anytime you're on Imuran, regardless of your sex.
  • If you stay on Imuran long-term, your healthcare provider will need to monitor you for potential side effects and complications.

Neoral/Gengraf (cyclosporine)

Cyclosporine, under several brand names, has been on the market since 1983. Neoral and Gengraf are often used for the treatment of RA and other autoimmune conditions.

Another brand, Sandimmune, has a different level of bioavailability and therefore cannot be used interchangeably with Neoral and Gengraf.

Neoral/Gengraf is available in soft gel capsule and liquid forms.


Cyclosporine was originally approved to combat post-transplant organ rejection. Later, the form of the drug in Neoral and Gengraf gained approval for treating:

Cyclosporine is used off-label for treating conjunctivitis, Langerhans cells histiocytosis, autoimmune hepatitis, Duchenne muscular dystrophy, ulcerative colitis, and other diseases.

Special Considerations

  • Cyclosporine comes with four black box warnings. The first is in regards to the different brands of the drug not being equivalent.
  • Second black warning: Due to its effects on the immune system, cyclosporine increases your risk of developing serious infections or cancer, especially lymphoma. This risk is increased if you're also taking other immunosuppressants such as azathioprine or methotrexate.
  • Third black box warning: Cyclosporine may cause high blood pressure and may damage your kidneys. The risk may be increased if you're taking other medications that may cause kidney damage, including Tagamet (cimetidine), Cipro (ciprofloxacin), Aleve (naproxyn), or Zantac (ranitidine).
  • Black box warning four: If you have psoriasis, your risk of developing skin cancer while on cyclosporine is increased if you have ever been treated with psoralen and UVA (PUVA), coal tar, immunosuppressants, or certain other treatments.
  • When taken during pregnancy, cyclosporine may increase the risk of premature birth, low birth weight, and miscarriage.
  • This drug does pass into breast milk and breastfeeding is not recommended while taking it.

Plaquenil (hydroxychloroquine)

Plaquenil has been available since 1955 and was originally used to treat malaria. For a short time in 2020, the FDA gave it an emergency use authorization to treat COVID-19, but that authorization was revoked after a large clinical trial found it wasn't beneficial.

This drug is available in tablet form.


Plaquenil is approved for treating:

It's used off-label for treating pediatric forms of lupus, lupus nephritis, Sjögren's syndrome, other autoimmune diseases, and rash caused by sun sensitivity (polymorphous light eruption).

Special Considerations

  • Plaquenil is known to cause severe hypoglycemia (abnormally low blood sugar) which can cause a loss of consciousness and can be life-threatening. If you have diabetes, your medications may need to be adjusted.
  • In rare cases, Plaquenil is associated with maculopathy, which can lead to blindness.
  • Other serious side effects include rash, tinnitus (ringing in the ears), muscle weakness, irregular heartbeat, and decreased/loss of consciousness.
  • Plaquenil isn't associated with fetal harm during pregnancy. However, it's not recommended while breastfeeding because the drug is passed on through breast milk and can be toxic to the baby. It is, however, sometimes prescribed during pregnancy in certain conditions, like SLE and Sjogren's syndrome, to improve maternal and fetal outcomes.

Rheumatrex/Trexall/RediTrex (methotrexate)

Known best by its generic name, methotrexate was FDA approved in 1953. This drug is the first-line therapy for moderate-severe RA. It's also widely used for treating psoriasis and cancer. A new injectable version, called RediTrex, gained approval in late 2019.

Serious warnings that come with the drug.

Methotrexate is available in tablets and an injectable liquid form.


Methotrexate is approved to treat:

  • Severe, active rheumatoid arthritis in people who've not improved with NSAIDs
  • Polyarticular juvenile idiopathic arthritis (pJIA) in children who've not improved with NSAIDs
  • Severe, recalcitrant, disabling psoriasis that hasn't improved with other therapies, but only when the diagnosis has been confirmed by biopsy or dermatologic consultation
  • Multiple types of cancer

RediTrex is not approved to treat cancer, but its indications are the same for RA, pJIA, and psoriasis.

Special Considerations

  • Medication adherence is imperative. People sometimes get confused and take methotrexate daily instead of weekly. This can lead to fatal side effects.
  • Methotrexate comes with 11 black box warnings from the FDA. They relate to: toxic reactions and death, embryo-fetal toxicity and death, bone marrow suppression, liver toxicity, lung disease, intestinal perforation, malignant lymphomas, tumor lysis syndrome, severe skin reactions, opportunistic infections, and tissue necrosis.
  • Routine monitoring of blood counts and liver and kidney function is required while you're on this drug.
  • Methotrexate may impair fertility in both men and women. It's unknown whether this is temporary or permanent.

Biologics, Biosimilars, and JAK Inhibitors

Three newer types of DMARDs are now on the market. These may be tried after you've tried an older DMARD or used as combination therapy with an older DMARD without adequate improvement.


Biologics are drugs derived from living cells. They often work by blocking certain enzymes. For example, some biologics are TNFα inhibitors because they block the action of immune-system cells called tumor necrosis factor-alpha, which are associated with RA and other autoimmune disorders.

Common biologics:


Biosimilars are based on existing biologics. The FDA considers them to have no significant differences from their original reference drugs, but they can be less expensive. You can recognize them by the four-letter suffix after their generic name.

Common biosimilars include:

JAK Inhibitors

These drugs inhibit the activity of Janus kinase enzymes, which are involved in inflammation and autoimmunity.

Common JAK inhibitors are:

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. U.S. Food and Drug Administration: FDA AccessData. Arava: Highlights of prescribing information and Full prescribing information.

  2. Levy RA, de Jesús GR, de Jesús NR, Klumb EM. Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactationAutoimmun Rev. 2016;15(10):955-963. doi:10.1016/j.autrev.2016.07.014

  3. U.S. Food and Drug Administration: FDA AccessData. Azulfidine.

  4. Arthritis Foundation. DMARDs.

  5. U.S. Food and Drug Administration: FDA AccessData. CellCept: Highlights of prescribing information and Full prescribing information.

  6. U.S. Food and Drug Administration: FDA AccessData and Merck & Co., Inc. Cuprimine (penicillamine).

  7. U.S. Food and Drug Administration: FDA AccessDate and Novartis. Sandimmune prescribing information.

  8. National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Cyclosporine.

  9. U.S. Food and Drug Administration: FDA AccessData and Novartis. Neoral prescribing information.

  10. U.S. Food and Drug Administration. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems.

  11. U.S. Food and Drug Administration: FDA AccessData. Methotrexate tablets, USP.

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.