DMARDs, or disease modifying antirheumatic drugs, slow down or even stop the progress of rheumatoid arthritis. These drugs are "disease modifying" because they interfere with the natural course of the disease. Except for their effect on RA, DMARDs are very dissimilar drugs. Most DMARDs were originally developed to treat other diseases and were only accidentally found to be effective for RA. DMARDs are also called slow-acting antirheumatic drugs (SAARDs) because it generally takes between one and six months before their effect is evident.

Until recently, rheumatoid arthritis has been treated with a pyramidal approach to drug therapy. NSAIDs (non-steroidal anti-inflammatory drugs) were used first, and the stronger DMARDs were only incorporated when evidence of joint destruction was seen. Working through the drug pyramid usually took between 5 and 8 years.

Research has revealed that irreversible damage to joints and cartilage occurs during the first two years of RA. Treating patients under the old paradigm meant using the weakest drugs while the most severe destruction was taking place. Armed with this new understanding about joint destruction, doctors now approach RA with a different treatment paradigm.

Today early aggressive intervention with DMARDs is recommended for all patients with moderate or severe disease. This preventative approach minimizes damage to the joints, reduces inflammation and preserves the patient's ability to function. Patients respond differently to the various DMARDs and sometimes several drugs must be tried before one is found to be effective. The cost of the drug, potential side effects and interaction with other medications must also be considered when selecting a DMARD.

The most commonly prescribed disease modifying drugs include:

Methotrexate (Rheumatrex)

Methotrexate is the most frequently prescribed DMARD. Compared to other DMARDs, it works faster and has fewer side effects than most. Patients receive methotrexate once a week, either by mouth or by injection. Methotrexate is highly effective.

Hydroxychloroquine (Plaquenil)

This drug was originally developed to treat malaria. Doctors don't understand how it works against rheumatic diseases, but it is highly effective and well tolerated by some RA patients. It is the least toxic of all the DMARDs. Hydroxychloroquine must be taken for 3-6 months before it reaches its full effect. This drug is typically used for mild, slowly progressive RA.

Gold Auranofin (Ridaura); Aurothioglucose (Solganal); Aurothiomalate (Myochrysine)

Gold salts have been used to effectively treat RA for more than half a century, although how they work is not well understood. Gold salts can be administered either by intramuscular injection (Myochrysine or Solganal) or by capsules (Ridaura). Gold taken orally is less toxic than gold given by injection, but also less powerful. Gold injections may not be fully effective until after 3-6 months of treatments.

Leflunomide (Arava)

Arava was approved by the Food and Drug Administration in September of 1998, making it the first new DMARD to receive approval in more than a decade. Arava works by suppressing an enzyme involved in the formation of DNA and RNA in the immune cells responsible for inflammation. Arava tablets must be taken for up to four weeks before a benefit is noticed.

Sulfasalazine (Azulfidine)

Sulfasalazine was developed in the 1930's specifically for treating RA. In the early 1940's it was widely used until gold treatments became more popular. It regained favor as a treatment for RA and was approved by the Food and Drug Administration in 1950. In Europe, this drug is still the most popular treatment for mild or moderate RA.

Sulfasalazine tablets must be taken for at least 4 weeks, but sometimes for as long as 20 weeks, before an effect is seen. This drug works after being broken down by bacteria in the colon. There is an anti-inflammatory effect that particularly benefits the colon, and for this reason Sulfasalazine is also used to treat colitis. It is often a good choice for RA patients who have been unresponsive to methotrexate.

Etanercept (Enbrel)

Enbrel is a genetically engineered drug that was approved by the FDA in November of 1998. This man-made drug binds to a protein called tumor necrosis factor (TNF) which the body produces whenever there is inflammation. Enbrel acts like a sponge, removing the TNF molecules from the joints and also from the blood. Inflammation, fever, tenderness and swelling are reduced in the absence of TNF. Recent data suggest that Enbrel is as effective as methotrexate. Enbrel is administered twice a week by subcutaneous injection. It may take several weeks before results are seen. This drug is very effective, but its benefits don't persist if the patient stops taking the drug. Enbrel is expensive, but it may be a good choice for patients who have been unresponsive to other DMARDs.

Oral corticosteroids (Deltasone, Orasone)

Low doses of oral prednisone or other corticosteroids are often given to RA patients to reduce inflammation. Corticosteroids may be used instead of NSAIDs in order to avoid the gastrointestinal problems caused by NSAIDs. Corticosteroids also have a disease modifying effect. These drugs significantly slow joint erosion. Recent studies show that this disease modifying effect does not persist if the drug is stopped, even if the patient has been taking it for years. If the drug is stopped patients may get worse.

Over time, all DMARDS lose their effectiveness. Most drugs benefit patients for only 2-5 years. One of the best ways to prolong the effectiveness of a drug is to combine it with other drugs. Combining one or more drugs with methotrexate, the "anchor drug" in RA therapy, often yields very positive results. Some successful combinations include:

Methotrexate and Infliximab (Remicade)

Remicade is a man-made drug that has been used for treating Crohn's disease. In November, 1999 it was approved by the FDA for rheumatoid arthritis, when used with methotrexate. This combination may work for people with hard to treat RA, or for those who were unresponsive to methotrexate alone.

Methotrexate and Enteracept

For some people, this combination yields dramatic results, with very few side effects.

Methotrexate, Sulfasalazine, and Prednisolone

One recent study found that this drug combination controlled symptoms for more than 70% of patients.

Methotrexate, Hydroxychloroquine and Sulfasalazine

This triple drug combination is, in some people, more effective than any one of these drugs by itself.

Methotrexate and Cyclosporine (Sandimmune)

Cyclosporine is a drug that suppresses the immune system. The combination of methotrexate and cyclosporine may be effective for patients who do not respond to methotrexate alone. The effects of this drug combination persist for 6 months after patients stop the drugs.

References

First published July 15, 2003
Copyright © 1999 Accordant Health Services, Inc. All Rights Reserved.

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