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Studies to date in this area have often been very small and are limited by including only specific groups of independent variables, such as demographic characteristics, disease activity, or genetic factors 8– 10. The overall predictive ability of these factors was relatively weak. In determining treatment strategy of patients treated with MTX, the characteristics of poor prognosis should be considered, such as female gender and persistent disease activity. Since many NSAID are bought over the counter, it is important to advise patients to inform their rheumatologist beforehand when considering buying over the counter medication. Although there are differences in the recommendations established by the Canadian rheumatologists versus the BSR/BHPR, the overall consensus is that NSAID can be used safely in combination with MTX as long as monitoring is performed regularly, especially for increased liver enzymes and cytopenia. British Society for Rheumatology/British Health Professionals in Rheumatology (BSR/BHRP) guidelines 7, in addition to those noted by the Canadian group, included a warning about the use of phenytoin, which may increase the antifolate effect of MTX probenecid and penicillin, which may reduce MTX excretion and tolbutamide, which may increase MTX serum concentration.
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This may explain why a similar exercise in the United Kingdom has resulted in slightly different recommendations on potential drug interactions, based on how much weight is given to each report. Indeed, the evidence base for Recommendation 1 was relatively scarce and was based on many case reports and case series. Defining drug interactions can be challenging, particularly among patients who may be receiving multiple medications. Trimethoprim and sulfamethoxazole (TMP-SMX) should be avoided in patients treated with MTX. The majority of the drugs including nonsteroidal antiinflammatory drugs (NSAID) may be used safely in combination with MTX in rheumatic diseases. 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.
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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 women 5. During this meeting 10 questions were addressed by rheumatologists from 17 countries in Europe and North and South America. 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. 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.
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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 RA 4. 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/week 3. The first, larger studies showing efficacy of MTX treatment in patients with RA were published in 1985 1, 2. Methotrexate (MTX) has been on the market for the treatment of rheumatoid arthritis (RA) for some decades.