The use of methotrexate in rheumatoid arthritis.
OBJECTIVE
To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs).


METHODS
Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease.


RESULTS
MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results.


CONCLUSIONS
MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, 95616, USA.
Andrea T
AT
Borchers
Carl L
CL
Keen
Gurtej S
GS
Cheema
M Eric
ME
Gershwin
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010147:Pain Measurement; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate