Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis affecting almost two million Americans. It is a chronic autoimmune systemic disease for which there is no cure yet. It is also associated with a higher morbidity and mortality compared with the general population as a result of increased cardiovascular events such as heart attacks and strokes.
However, advance over the last 30 years have permitted rheumatologists to get RA into remission in a great number of instances.
Probably one of the medicines that has made the most difference is methotrexate (MTX). This is a disease modifying anti-rheumatic drug that was first used in the early 1980's and is considered the "base drug" upon which other therapies are added.
MTX was first used in the oncology field. Its effect is to inhibit cellular metabolism and the proliferation (multiplication) of cells. Besides this anti-proliferative effect, MTX also has an a modest immunosuppressive effect.
Typically, a new patient with rheumatoid arthritis is immediately started on MTX in combination with either low dose prednisone or a non-steroidal anti-inflammatory drug (NSAID). Doses start at 7.5 mgs or 10 mgs per week given as a single dose once a week. The maximum dose we use is about 20 mgs. Some rheumatologists prefer to add on other DMARDS such as sulfasalazine (Azulfidine) or hydroxychloroquine (Plaquenil) or both.
Many other rheumatologists, however, prefer to add a biologic drug to MTX. I fall into this latter group.
MTX has been demonstrated to have two beneficial effects above and beyond the relief of symptoms. It has been shown to slow down the rate of x-ray progression which is a key determinant of eventual disability and also to potentially reduce the mortality associated with cardiovascular events.
It is generally safe. There are potential side effects including mouth ulcers, nausea, hair loss and more serious side effects such as potential liver damage and suppression of white blood cell count. Another issue is lung toxicity which can come on suddenly and is referred to as "methotrexate lung" or more insidiously leading to eventual fibrosis of the lungs. Patients with underlying liver disease such as hepatitis B and C should probably not receive the drug if possible.
Supplementation with folic acid can prevent or reduce the severity of many of the minor side effects. Close laboratory monitoring is mandatory. Patients with kidney disease should be monitored particularly closely and lower doses of MTX should be used since MTX toxicity increases with declining kidney function.
When patients develop infections of any sort, we recommend holding the MTX until they have recovered. For patients scheduled to have surgery we recommend they hold the MTX one week before and one week after the operation before resuming the drug.