Methotrexate and other DMARDs –Modulate Immune Response

Category: Medications & Supplementation Published on Tuesday, 31 March 2015 Written by Yong Tsai, MD

The strategic plan in treating rheumatoid arthritis (RA) has changed from a conventional process of using NSAIDs and corticosteroids to control symptoms, to a more biological modifying process by adding disease-modified anti-rheumatic drugs (DMARDs) to the preceding to alter the inflammatory process and prevent joint damage. This is one of the milestones in the treatment of RA.

Since the mid-1980s, Methotrexate (MTX) has become the more popular treatment for RA because of its effectiveness and ability to work more rapidly than other DMARDs. At present, MTX is the first line treatment for RA and psoriatic arthritis. MTX is an anti-metabolite that interferes with the way cells utilize essential nutrients, which in this case is folic acid. In addition to its ability to inhibit the activity of our immune system and reduce inflammation associated with RA and psoriatic arthritis (PsA), MTX can also slow the growth of cancer cell when prescribed in a different dose and schedule. Therefore, the use of MTX in the treatment of RA is not regarded as a form of “chemotherapy".

Depending on the patient, MTX can be taken as a pill by mouth or as an injection. Because it takes up to four weeks to take effect, NSAIDs (non-steroidal anti-inflammatory drugs) or corticosteroids are usually continued to control your symptoms. However, when the MTX kicks in, these medications may be decreased. Common side effects may include nausea, vomiting, loss of appetite, and mouth ulcers. However, these side effects can decrease and even disappear with usage, especially adding folic acid during MTX treatment. One important side effect that needs to be closely monitored is the very rare complication of liver damage. Frequent laboratory monitoring will largely keep side effects from occurring.

MTX should not be taken while you are pregnant or breastfeeding. Furthermore, because alcohol and MTX both have the potential to affect your liver, it is advised that alcohol consumption be reduced or even eliminated. Since DMARDs often take from several weeks to several months to work, trying them requires patience, commitment, and time. Once your symptoms are under control, you may have to stay on DMARDs for a long period of time, though your doctor may try to decrease the dosage.

Other DMARDs such as leflunomide, sulfasalazine and hydroxychloroquine have similar safety profile but not as effectiveness as MTX. Combined two or even three DMARDs is also effectiveness for patients with inadequate response to MTX only. Despite the powerfulness of DMARD drugs, only 40-50 percent of patients respond well to treatment. Even though they can slow down the progression of joint damage, the results are still unsatisfactory. New biologic agents offer new hope for patients with moderate to severe RA and PsA.

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