Table 2 Initiation of MTX therapy: main findings from included RCT
Author, year | Treatment groups | Study duration (weeks) | Relevant efficacy findings | Relevant safety findings |
|---|---|---|---|---|
Comparing different initial doses | ||||
A: Oral MTX 7.5 mg/week; B: Oral MTX 15 mg/week | 12 | No statistically significant differences for: Mean change in DAS28 (p = 0.60), HAQ score (p = 0.22), Tender joint counts, Swollen joint counts, Erythrocyte sedimentation rate, Patient-rated improvement | No statistically significant differences for adverse effects: Transaminitis (p = 0.8) and, Cytopenia (p = 0.9). | |
Furst, 1989 [37] | A: Oral MTX 5 mg/m2/week; B: Oral MTX 10 mg/m2/week; C: Oral MTX 20 mg/m2/week | 18 | Linear dose-response relationship (placebo vs. 5 mg/m2 vs. 10 mg/m2) for: Patient pain and global patient scale, global physician scale, joint tenderness count and the activity of daily living scale (p < 0.05) | No statistically significant correlation between dose-to-toxicity |
Schnabel, 1994 [41] | A: Oral MTX 15 mg/week orally with dosage adjustment based on efficacy after 3 months; B: Oral MTX 25 mg/week orally with dosage adjustment based on efficacy after 3 months | 52 | Increase dose due to ineffectiveness: 27% (15 mg group) vs. 3% (25 mg group). Dose reduction due in part to remission: 23% (15 mg group) vs. 51% (25 mg group); p = 0.0001. | Dose reduction due to toxicity: 9% in both groups |
Comparing standard versus accelerated regimens for increasing oral MTX dosages | ||||
Hobl, 2012 [38] | A: Oral MTX 15 mg/week (standard group); B: Oral MTX 25 mg/week (accelerated group) | 16 | No statistically significant differences for: DAS28 (-1.8 vs. -2.0, p = 0.93) | Adverse events incidence: 60% (standard dosage group) vs. 56% (accelerated dosage group). (study was not powered to detect differences) |
Jain, 2021 [36] | A: Oral MTX 15 mg/week, + 5 mg/4 weeks (usual escalation group); B: Oral MTX 15 mg/week, + 5 mg/2 weeks (fast escalation group) | 16 | No statistically significant differences for: DAS28 (-1.3 vs. -1.3, p = 0.98) HAQ score (-0.8 vs. -0.7, p = 0.26) EULAR response (65.2% vs. 61.8%, p = 0.64) DAS28-CRP-based remission (14.6 vs. 13.5, p = 0.80) | Significantly more gastrointestinal AE in the fast escalation group at 8 weeks (27%, 40%, p = 0.048), but not at 16 weeks |
Tsutsumino, 2017 [33] | A: Oral MTX, + 0.25 mg/kg/week up to maximum tolerable dose; B: Oral MTX (conventional treatment group) | 24 and 48 | No statistically significant differences for: HAQ score (-0.8 vs. -0.56, p = 0.096) SDAI remission (42% vs. 28%, p = 0.1), HAQ (0 vs. 0.13, p = 0.096) EuroQol-5D (0.78 vs. 0.77, p = 0.12) | No significant differences in incidence of severe adverse events |
Comparing different routes of administration for MTX | ||||
Braun, 2008 [34] | A: Oral MTX 15 mg/week with dosage adjustment after 16 weeks based on efficacy; B: SC MTX 15 mg/week with dosage adjustment after 16 weeks based on efficacy | 24 | ACR20 response was statistically higher in SC MTX (85%) versus 77% in the oral MTX group (P < 0.05) | |