Methotrexate for Rheumatoid Arthritis: A Guide from Canada

Abstract

Methotrexate (MTX) has been on the market for the treatment of rheumatoid arthritis (RA) for some decades. The first, larger studies showing efficacy of MTX treatment in patients with RA were published in 19851,2. In 1986 the US Food and Drug Administration approved the drug for the treatment of RA, starting MTX therapy at an initial test dose of 2.5 mg to establish hematologic tolerance to a maximum of 20 mg/week3. Since then, MTX has increasingly been prescribed for patients with RA and is now considered by many to be the disease-modifying drug (DMARD) of first choice for most patients with RA4. To develop practical recommendations for the use of MTX in rheumatic diseases, the 3E initiative (Evidence, Expertise, Exchange) set up an international consensus meeting 2007–2008. The aim of this meeting was to define recommendations for MTX use in daily practice according to evidence-based medicine, by integrating systematically generated evidence from the literature with expert opinion. During this meeting 10 questions were addressed by rheumatologists from 17 countries in Europe and North and South America. Published recommendations cover starting dose and escalation dose of MTX, prescription of at least 5 mg folic acid with MTX therapy, adjustment or discontinuation of MTX therapy in case of persistent elevated liver enzyme levels, and discontinuation of MTX prior to planned pregnancy in men and women5. Next to these internationally chosen recommendations, the Canadian rheumatologists addressed 5 additional questions on drug interaction, monitoring, predictors of response, patients’ preference, and management of nuisance side effects; their recommendations are reported in this issue of The Journal 6. ### Recommendation 1 The majority of the drugs including nonsteroidal antiinflammatory drugs (NSAID) may be used safely in combination with MTX in rheumatic diseases. Trimethoprim and sulfamethoxazole (TMP-SMX) … Address correspondence to Dr. Verstappen; E-mail: suzanne.verstappen{at}manchester.ac.uk