Rheumatoid arthritis is the most common inflammatory form of arthritis. It affects more than 2 million Americans. Because it is a systemic disease capable of damaging internal organs, it must be and usually is treated very aggressively.

The most widely prescribed disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis is methotrexate.

It has been in use since the early 1980's and is the "gold standard" by which rheumatologists judge all other DMARDS. It is also the drug upon which other medicines such as biologic response modifiers (BRMS) are added.

Methotrexate interferes with folic acid metabolism by blocking a specific enzyme called dihydrofolate reductase. Dihydrofolate reductase is required for the growth of actively dividing cells. Since inflammation is perpetuated by rapidly growing cells, methotrexate is felt to exert its effects by blocking the multiplication or proliferation of these cells.

As a result of its actions, methotrexate reduces the swelling and pain associated with rheumatoid arthritis and also decreases the risk of long term disability. It takes roughly 4-12 weeks to see the maximum effects of methotrexate. During this short period of time, the dose of methotrexate is started at a low dose and gradually increased.

The drug can be administered in several ways. Patients who have extremely active disease can be treated intravenously to help with induction of remission. Patients can then be treated with oral tablets. The tablets come in a dose of 2.5 mgs per tablet. Methotrexate is taken as a single dose of medicine once a week. That means that if a patient is taking the drug either intravenously or in tablet form, they take all their medicine at one time once a week. Some patients who have difficulty taking oral tablets because of nausea may be able to take their methotrexate as a subcutaneous injection.

The dose of methotrexate varies from a low of 5 mgs per week to as high as 25 mgs per week. Higher doses tend to be poorly tolerated.

Potential side effects include mouth sores, gastrointestinal problems such as nausea, vomiting, and diarrhea, shortness of breath, cough, liver function abnormalities, hair loss, sun sensitivity, and drops in white blood cell count or platelet count. Rarely, cirrhosis of the liver can occur. Older people who have dietary deficiencies are at particular risk for methotrexate side effects.

Patients should have laboratory testing of blood counts and liver function tests once a month.

Patients are usually given supplemental folic acid in a dose of 1-2 mgs per day to counteract some of the side effects of methotrexate.

Methotrexate is terribly teratogenic (capable of causing birth defects). Therefore, in women, as well as men, who are contemplating having children, patients need to hold their methotrexate for at least 3 months prior to attempting conception.

Since methotrexate is capable of damaging the liver, patients should be counseled about limiting or eliminating alcohol ingestion.

Furthermore, methotrexate can interact with a number of other medicines including antibiotics such as sulfa drugs as well as non-steroidal anti-inflammatory drugs.

Methotrexate is often used in combination with biologic drugs such as Enbrel, Humira, and Remicade.