Methotrexate For Rheumatoid Arthritis
- In the 1940's, methotrexate was developed for leukemia therapy.
- The first attempt to use it against rheumatoid arthritis was reported in 1951.
- In the years that ensued, studies were conducted to determine the effectiveness and safety of methotrexate for the treatment of rheumatoid arthritis.
- In the 1970's, methotrexate was considered an experimental treatment for rheumatoid arthritis, it is now an FDA-approved drug.
Intially, methotrexate was prescribed for patients who did not respond to other therapies. Patients were subsequently prescribed methotrexate when they were not helped by nonsteroidal anti-inflammatory drugs (NSAIDs) or by one of the other disease-modifying anti-rheumatic drugs (DMARDs) such as:
Over the course of time, the trend for treatment of rheumatoid arthritis has gone from a conservative approach to the belief that early, aggressive treatment is imperative. Methotrexate has since become the gold standard treatment for patients who have moderate to severe rheumatoid arthritis with pain, stiffness, swelling, and fatigue.
Treatment Schedule
Methotrexate may be taken orally in tablet form. The entire weekly dose is usually given once a week, frequently in divided doses over a 24-hour period, or it can be taken in one dose. Methotrexate is usually prescribed in addition to other treatments, not instead of them.
To avoid possible gastrointestinal upset interfering with the patient's work week, Saturday is often chosen as the treatment day. Methotrexate can also be injected intramuscularly and this eliminates the gastrointestinal upset for many people.
Studies have indicated that methotrexate used in combination with another cytotoxic drug (i.e. Imuran, Cytoxan), or in combination with Enbrel (etanercept), may be more beneficial than methotrexate used alone for some people. Studies have also revealed than methotrexate given earlier in the course of treatment may provide a better result.
How Methotrexate Works
Methotrexate is an antimetabolite. It interferes with the way cells utilize essential nutrients. As a result, methotrexate inhibits the activity of the immune system, consequently reducing inflammation. As a cytotoxic drug it may slow the rapid growth of cells in the synovial membrane that lines the joints.
Methotrexate is a potent drug and many have feared its potential toxicity and questioned its safety. Over the last decade, the drug has proved to be safer than expected. The toxic reactions have not appeared as frequently or severely as had been feared due probably to the low dosage level used for arthritis, 1/100 the amount used for cancer chemotherapy.
Methotrexate is a long-term treatment. Dramatic improvement seems to occur in patients within the first month or two. Steady improvement continues for many people over months or even years. When the drug is withdrawn, as has been done in studies, all signs of improvement disappear and a flare-up of symptoms occurs within a few weeks.
Side Effects
The most common side effect of methotrexate is nausea. The nausea from methotrexate use often disappears on its own though and may be controlled by lowering the dose or spreading the dose out.
The drug can cause hidden problems too and tests are done to monitor whether or not these problems are occurring. Complete blood counts are done since methotrexate can suppress the production of new blood cells and lead to severe forms of anemia. Liver-chemistry profiles are done to watch for possible effects on the liver. Liver damage is among the worst potential problems since once the damage is done it is irreversible. Since most serious damage to the liver is not revealed in a blood test, a liver biopsy may be recommended periodically.
Another potential threat from methotrexate use is lung disease. Dry cough accompanied by fever and shortness of breath could indicate such a problem. Hair loss is seen in some patients. Some people who use methotrexate develop sores on their skin and inside their mouths. These are signs of a toxic reaction to the drug and its use may need to be discontinued.
According to the American College of Rheumatology, "the use of folate supplements (folic and folinic acid), which are B vitamins, can decrease side effects during methotrexate treatment."
Warnings
Women should not take methotrexate if they are pregnant or planning to become pregnant. Men planning to become fathers also are warned that the drug may cause birth defects and sterility. Methotrexate use is also ruled out for people who drink a lot of alcohol since the danger of liver cirrhosis then rises significantly.
Related Resources
Sources: Arthritis What Works, by Dava Sobel & Arthur C. Klein; The Duke University Medical Center Book Of Arthritis, David S. Pisetsky, M.D.; Methotrexate, American College of Rheumatology, 4/2004
