Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?
Methotrexate (MTX) is the anchor disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA) treatment. It is used in monotherapy and/or in combination with other synthetic or biological DMARDs, and is known to have the best cost-effectiveness and efficacy/toxicity ratios. However, toxicity is still a concern, with a significant proportion of patients interrupting long-term treatment due to the occurrence of MTX-related adverse drug reactions (ADRs), which are the main cause of drug withdrawal. Despite the extensive accumulated experience in the last three decades, it is still impossible in routine clinical practice to identify patients prone to develop MTX toxicity. While clinical and biological variables, including folate supplementation, partially help to minimize MTX-related ADRs, the advent of pharmacogenomics could provide further insight into risk stratification and help to optimize drug monitoring and long-term retention. In this paper, we aimed to review and summarize current data on low-dose MTX-associated toxicity, its prevention and predictors, keeping in mind practical RA clinical care.
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon Academic Medical Centre, Edifício Egas Moniz, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Vasco C
VC
Romão
Aurea
A
Lima
Miguel
M
Bernardes
Helena
H
Canhão
João Eurico
JE
Fonseca
D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D019587:Dietary Supplements; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D010597:Pharmacogenetics; D011379:Prognosis; D015398:Signal Transduction
D018501:Antirheumatic Agents; D002352:Carrier Proteins; D005492:Folic Acid; D008727:Methotrexate