Patient information: Disease-modifying antirheumatic drugs (DMARDs) (Beyond the Basics)
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
DISEASE-MODIFYING ANTIRHEUMATIC DRUG OVERVIEW
Disease-modifying antirheumatic drugs (DMARDs) are a group of medications commonly used in patients with rheumatoid arthritis. They work to decrease pain and inflammation, to reduce or prevent joint damage, and to preserve the structure and function of the joints. Some of these drugs are also used in treating other conditions such as ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus. (See "Patient information: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)" and "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)" and "Patient information: Complementary and alternative therapies for rheumatoid arthritis (Beyond the Basics)".)
WHAT ARE DISEASE-MODIFYING ANTIRHEUMATIC DRUGS?
DMARDs work to suppress the body's overactive immune and/or inflammatory systems. They take effect over weeks or months and are not designed to provide immediate relief of symptoms.
Other medicines, such as pain relievers, nonsteroidal antiinflammatory drugs (eg, ibuprofen or naproxen), and, sometimes, prednisone, are given to provide faster relief of ongoing symptoms. DMARDs are often used in combination with these medications to reduce the total amount of medication needed and to prevent damage to joints.
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
The choice of DMARD depends on a number of factors, including the stage and severity of the joint condition, the balance between possible side effects and expected benefits, and patient preference. Before treatment begins, the patient and clinician should discuss the benefits and risks of each type of therapy, including possible side effects and toxicities, dosing schedule, monitoring frequency, and expected results.
In some cases, one DMARD is used. In others, more than one medication may be recommended. Sometimes a patient must try different medicines or combinations to find one that works best and that has the fewest side effects. A patient who does not respond completely to a single DMARD may be given a combination of DMARDs, such as methotrexate plus another medication.
The most common DMARDs are methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide. Less frequently used medications include gold salts, azathioprine, and cyclosporine.
Methotrexate — Methotrexate was originally used as a chemotherapy treatment for cancer. When used in much lower doses for rheumatoid arthritis and other rheumatic diseases, methotrexate works to reduce inflammation and to decrease joint damage. It is usually taken once per week as a pill, liquid, or injection. Methotrexate may be combined with other DMARDs or with a biologic agent if methotrexate alone does not adequately control a patient's disease. (See 'Biologic agents' below.)
Common side effects include upset stomach and a sore mouth. Methotrexate can interfere with the bone marrow's production of blood cells. Low blood cell counts can cause fever, infections, swollen lymph nodes, and easy bruisability and bleeding. Liver or lung damage can occur, even with low doses, and, therefore, requires monitoring. People using methotrexate are strongly discouraged from drinking alcoholic beverages because of the increased risk of liver damage with this combination.
Monitoring reduces the risk of long-term damage from methotrexate. A chest x-ray is recommended before beginning treatment, and regular blood testing is recommended. While taking methotrexate, most patients take folic acid 1 mg daily or folinic acid 5 mg weekly to reduce the risk of certain side effects, such as upset stomach, sore mouth, low blood cell counts, and abnormal liver function.
Sulfasalazine — Sulfasalazine is used in the treatment of rheumatoid arthritis and of arthritis associated with ankylosing spondylitis and inflammatory bowel disease (ulcerative colitis and Crohn’s disease). It is not clear how sulfasalazine works. It may be combined with other DMARDs if a person does not respond adequately to one medication. It is taken as a pill two to four times per day, and it is usually started at a low dose and is increased slowly to minimize side effects.
Side effects of sulfasalazine include changes in blood counts, nausea or vomiting, sensitivity to sunlight, skin rash, and headaches. People who are allergic to sulfa drugs may have a cross reaction to sulfasalazine and should, therefore, not take it. Periodic blood tests are recommended to monitor the blood count on a regular basis.
Sulfasalazine is a yellow/orange color; patients who take it may notice that their urine, tears, and sweat develop an orange tinge, which can stain clothing and contact lenses. Patients should drink plenty of fluids while taking sulfasalazine and should avoid taking it on an empty stomach or with antacids.
Hydroxychloroquine — Hydroxychloroquine, originally developed as a treatment for malaria, was later found to improve symptoms of arthritis. It can be used early in the course of rheumatoid arthritis and is often used in combination with other DMARDs. It is also very frequently used for treatment of systemic lupus erythematosus. It can be combined with steroid medications to reduce the amount of steroid needed. It is usually taken in pill form once or twice per day.
Taking a high dose of hydroxychloroquine for prolonged periods of time may increase the risk of damage to the retina of the eye, although high doses are not usually required for treatment of rheumatoid conditions or lupus. An eye examination is recommended before starting treatment and periodically thereafter. It is common to have an eye check-up done once each year.
Leflunomide — Leflunomide inhibits production of inflammatory cells to reduce inflammation. It is often used alone but may be used in combination with methotrexate for people who have not responded adequately to methotrexate alone or together with a biologic agent. It is taken by mouth once daily.
Side effects include rash, temporary hair loss, liver damage, nausea, diarrhea, weight loss, and abdominal pain. Regular testing to monitor for liver damage is required.
Azathioprine — Azathioprine (AZA) has been used in the treatment of cancer, rheumatoid arthritis, lupus, and a variety of other inflammatory illnesses since the 1950s. It has also been used in organ transplantation to prevent rejection of the transplanted organ. AZA is generally reserved for patients who have not responded to other treatments.
The most common side effects of AZA include nausea, vomiting, decreased appetite, liver function abnormalities, low white blood cell counts, and infection. It is usually taken by mouth once to four times daily. Blood testing is recommended during treatment with AZA.
Cyclosporine — Cyclosporine was originally developed to prevent rejection after organ transplantation. It works in patients with rheumatoid arthritis to inhibit T lymphocytes, a cell that contributes to the inflammation associated with rheumatoid arthritis. There is concern about the long-term safety of cyclosporine and its association with kidney disease and high blood pressure, so it is generally reserved for patients who have not responded to other treatments. It is usually taken by mouth in pill or liquid form twice per day; an injectable form is also available. It is occasionally used to treat kidney disease due to lupus.
Side effects include high blood pressure, swelling, kidney damage, increased hair growth, nausea, diarrhea, and heartburn. Patients should have blood pressure and kidney function monitoring on a regular basis.
Another class of medications used in persons with rheumatoid arthritis and related inflammatory rheumatic conditions is biologic agents, sometimes called biologic DMARDs, including etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab, which are all part of a class of drugs called tumor necrosis factor (TNF) inhibitors, and a variety of other agents with different targets, including anakinra, abatacept , rituximab, tocilizumab, and tofacitinib. These medications are often combined with methotrexate or other DMARDs to improve efficacy. (See "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)", section on 'Biologic DMARDs'.)
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Rheumatoid arthritis (The Basics)
Patient information: Juvenile rheumatoid arthritis (The Basics)
Patient information: Ankylosing spondylitis (The Basics)
Patient information: Vasculitis (The Basics)
Patient information: Disease modifying antirheumatic drugs (DMARDs) (The Basics)
Patient information: Behçet’s syndrome (The Basics)
Patient information: Psoriatic arthritis in children (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)
Patient information: Rheumatoid arthritis treatment (Beyond the Basics)
Patient information: Complementary and alternative therapies for rheumatoid arthritis (Beyond the Basics)
Patient information: Rheumatoid arthritis and pregnancy (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
General principles of management of rheumatoid arthritis in adults
Overview of the use of immunosuppressive and disease-modifying drugs in the rheumatic diseases
Randomized clinical trials of combinations of nonbiologic DMARDs in rheumatoid arthritis
Initial treatment of mildly active rheumatoid arthritis in adults
Initial treatment of moderately to severely active rheumatoid arthritis in adults
Treatment of rheumatoid arthritis resistant to initial DMARD therapy in adults
The following organizations also provide reliable health information.
- National Library of Medicine
- The Arthritis Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- American College of Rheumatology
- American Academy of Family Physicians
- American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46:328.
- O'Dell JR, Leff R, Paulsen G, et al. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46:1164.
- Weinblatt ME, Reda D, Henderson W, et al. Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J Rheumatol 1999; 26:2123.
- Cohen SB, Iqbal I. Leflunomide. Int J Clin Pract 2003; 57:115.
- Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum 1990; 33:1449.
- Chambers CD, Tutuncu ZN, Johnson D, Jones KL. Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data. Arthritis Res Ther 2006; 8:215.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.