Table 1 Study and patient characteristics of trials included for direct comparisons of methotrexate dosages/routes
Study reference, design and qualityPatient characteristicsTreatment groups (methotrexate dosage/route)
Furst et al, 19898
    Double-blind RCTn  =  52Oral methotrexate 20 mg/m2/week ≈ 25–35 mg/week
    16-Week follow-upRA 4.8 yearsOral methotrexate 10 mg/m2/week ≈ 12.5–20 mg/week
    van Tulder score 10Failed gold orOral methotrexate 5 mg/m2/week ≈ 5–10 mg/week
    Evidence level 2bd-PenicillaminePlacebo
Methotrexate-naiveNo folic acid
Schnabel et al, 19949n  =  185Oral methotrexate 25 mg/week
    Open-label RCTRA 3–10 yearsOral methotrexate 15 mg/week
    52-Week follow-upPrevious DMARDIncrease or decrease if necessary
    van Tulder score 7Methotrexate-naiveNo folic acid
    Evidence level 2b
Verstappen et al, 200710n  =  299Fast escalation: oral methotrexate 7.5 mg/week+
    Open-label RCTRA <1 year5 mg/month to mean max 25 g/week (max 30)
    52-Week follow-upDMARD-naiveSlow escalation: oral methotrexate 7.5 mg/week+
    van Tulder score 75 mg/3 months to mean max 18 mg/week
    Evidence level 2bFolic acid
Lambert et al, 200411n  =  54Switch to intramuscular methotrexate:
    Double-blind RCTRA 10 years15 mg/week+ escalation 5 mg/month to max 45 mg/week
    22-Week follow-up    van Tulder score 9    Evidence level 2bFailed oral methotrexate 15–20 mg/week15 mg/week+ placebo escalationFolic acid
Braun et al, 200812    Double-blind RCT    24-Week follow-up    van Tulder score 11    Evidence level 1bn  =  375RA <1 yearsMethotrexate-naiveSubcutaneous methotrexate 15 mg/week, escalation to 20 mg/week if no ACR20 at 16 weeksOral methotrexate 15 mg/week, switch to 15 mg/week subcutaneously if no ACR20 at 16 weeksFolic acid
  • ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; RA, rheumatoid arthritis; RCT, randomised controlled trial.