The patient described above has moderate rheumatoid arthritis, poorly controlled with NSAIDs alone. Methotrexate is a commonly used disease modifying agent but should be avoided in those with liver disease as it can lead to the elevation of liver function tests, AST and ALT.
Low dose methotrexate is a commonly prescribed disease modifying antirheumatic drug (DMARD) used in the treatment of moderate to severe rheumatoid arthritis. Methotrexate inhibits the enzyme dihydrofolate reductase (DHFR) necessary for the production of folic acid and thus RNA and DNA synthesis. Even at low doses, side effects of methotrexate can be severe. It is contraindicated in pregnant and lactating women, as well as individuals with liver disease, immunodeficiency, blood dyscrasias, and known hypersensitivity to methotrexate.
Wasserman reviews the diagnosis and management of rheumatoid arthritis, including at-risk populations and diagnostic criteria and testing. In regard to treatment, he notes that methotrexate is first-line for those who are eligible. Second-line therapy includes biologic drugs. Patients are often maintained on a combination of medications.
Shea et al. undertook a systematic review of the evidence for folic acid as a method to decrease the side effects of methotrexate, which include mucosal, gastrointestinal, hepatic, and hematologic manifestations. They found that patients taking folic acid experienced a significant reduction in transaminase levels.
Illustration A depicts the mechanism of methotrexate. Illustration B shows the difference between a normal joint and a joint with rheumatoid arthritis.
Answer 1: Cyclosporine is a DMARD that works by inhibiting the enzyme calcineurin in lymphocytes, especially T-cells.
Answer 3: Corticosteroids are used in the treatment of rheumatoid arthritis and work by acting as a transcription factor to decrease inflammatory cytokine.
Answer 4: Hydroxyurea is a DMARD that works by inhibiting the enzyme ribonucleotide reductase essential in DNA synthesis.
Answer 5: Etanercept is a DMARD that works by inhibiting TNF-alpha.
Wasserman AM. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2011 Dec 1;84(11):1245-52.
PMID:22150658 (Link to Abstract)
Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, Bombardier C, Wells GA, Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013 May 31;5:CD000951.
PMID:23728635 (Link to Abstract)