Table 2 Odds ratios (95% CI) of clinical and toxicity outcomes of trials directly comparing different methotrexate dosages/routes
Study + comparisonPatients with AEWithdrawal for toxicityPulmonalHepatotoxicityBone marrowInfectionsGastrointestinalMucocutaneousACR20/ACR50
Furst et al8
    25–35 mg/week8.3†7.5†0003.011.0*7.0†NA
    vs placebo(0.8 to 89.5)(0.5 to 105.3)(0.2 to 57.4)(1.0 to 120.4)(0.8 to 62.0)
    12.5–20 mg/week5.4*0.90.90.92.05.3*4.9†NA
    vs placebo(1.2 to 24.5)(0.1 to 16.4)(0.1 to 16.4)(0.1 to 16.4)(0.2 to 24.5)(1.2 to 23.3)(0.8 to 28.7)
    5–10 mg/week5.6*02.71.31.33.5†3.1NA
    vs placebo(1.1 to 28.6)(0.2 to 34.0)(0.1 to 22.1)(0.1 to 22.1)(0.8 to 16.4)(0.5 to 20.7)
    12.5–20 mg/week1.00.30.80.81.61.51.8NA
    vs 5–10 mg/week(0.2 to 5.4)(0.03 to 4.3)(0 to 13.2)(0 to 13.2)(0.1 to 19.8)(0.3 to 6.9)(0.3 to 7.2)
Schnabel et al9
    25 mg/weekNA1.1NA1.31.8NA1.8†NANA
    vs 15 mg/week(0.5 to 2.5)(0.7 to 2.3)(0.3 to 11.0)(0.9 to 3.8)
Verstappen et al10ACR50
    Fast vs slow2.3*1.80.41.31.9NA1.00.81.8*
    escalation(1.02 to 5.3)(0.8 to 4.0)(0.1 to 1.4)(0.7 to 2.3)(0.7 to 5.2)(0.6 to 1.7)(0.4 to 1.4)(1.1 to 2.8)
Lambert et al11ACR20
    Intramuscular 15–45 mg/weekNA1.01.51.0NA1.42.41.0
    vs 15 mg/week(0.1 to 16.9)(0.4 to 5.6)(0.1 to 16.9)(0.5 to 4.4)(0.6 to 9.3)(0.1 to 16.9)
Braun et al12ACR20
    Subcutaneous vs oral1.22.3†0.60.4NA0.91.20.81.5†
    15 mg/week(0.8 to 1.9)(0.98 to 5.5)(0.2 to 1.9)(0.1 to 1.4)(0.4 to 2.2)(0.8 to 1.7)(0.3 to 2.5)(0.96 to 2.4)
  • *Odds ratio (OR) is significant; †OR shows a trend, ∞, comparator group has zero events; ACR, American College of Rheumatology; AE, adverse event; NA, not available.