Study reference, design and quality | Patient characteristics | Treatment groups (methotrexate dosage/route) |
Furst et al, 19898 | ||
Double-blind RCT | n = 52 | Oral methotrexate 20 mg/m2/week ≈ 25–35 mg/week |
16-Week follow-up | RA 4.8 years | Oral methotrexate 10 mg/m2/week ≈ 12.5–20 mg/week |
van Tulder score 10 | Failed gold or | Oral methotrexate 5 mg/m2/week ≈ 5–10 mg/week |
Evidence level 2b | d-Penicillamine | Placebo |
Methotrexate-naive | No folic acid | |
Schnabel et al, 19949 | n = 185 | Oral methotrexate 25 mg/week |
Open-label RCT | RA 3–10 years | Oral methotrexate 15 mg/week |
52-Week follow-up | Previous DMARD | Increase or decrease if necessary |
van Tulder score 7 | Methotrexate-naive | No folic acid |
Evidence level 2b | ||
Verstappen et al, 200710 | n = 299 | Fast escalation: oral methotrexate 7.5 mg/week+ |
Open-label RCT | RA <1 year | 5 mg/month to mean max 25 g/week (max 30) |
52-Week follow-up | DMARD-naive | Slow escalation: oral methotrexate 7.5 mg/week+ |
van Tulder score 7 | 5 mg/3 months to mean max 18 mg/week | |
Evidence level 2b | Folic acid | |
Lambert et al, 200411 | n = 54 | Switch to intramuscular methotrexate: |
Double-blind RCT | RA 10 years | 15 mg/week+ escalation 5 mg/month to max 45 mg/week |
22-Week follow-up van Tulder score 9 Evidence level 2b | Failed oral methotrexate 15–20 mg/week | 15 mg/week+ placebo escalationFolic acid |
Braun et al, 200812 Double-blind RCT 24-Week follow-up van Tulder score 11 Evidence level 1b | n = 375RA <1 yearsMethotrexate-naive | Subcutaneous 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.