Table 3 Optimisation of MTX therapy: Main findings from included RCT
Author, year | Treatment groups | Study duration (weeks) | Relevant efficacy findings | Relevant safety findings | |
|---|---|---|---|---|---|
Comparing different MTX doses after initial failure to 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 | Increased ACR20 response in an additional 23% of participants treated with 20 mg of SC MTX | ||
Verstappen, 2007 [35] | A: Oral MTX 7.5 mg/week, + 5 mg/month (Intensive strategy group); B: Oral MTX 7.5 mg/week + 5 mg/3 months (conventional strategy group) | 52 | Statistically significantly higher sustained remission rate for the intensive strategy group at: 1 year (35% vs. 14%, p < 0.001), and 2 years (50% vs. 35%, p = 0.03). Mean time to sustained remission about 4 months shorter in the intensive strategy group (10.4 months vs. 14.3 months; p < 0.001). | Adverse events incidence: 87% (conventional strategy group) vs. 94% (intensive strategy group). | |
Lambert, 2004 [39] | A: Oral MTX to IM 15 mg/week for 6 weeks, then: MTX IM + 5 mg/4 weeks up to 45 mg (escalation group); B: Oral MTX to IM 15 mg/week for 6 weeks, then: IM MTX 15 mg/week (control group) | 22 | No statistically significant differences: DAS28 score (3.7% and 18.5% in each group achieved a DAS28 score of < 3.2, and an improvement of > 1.2, respectively) ACR20 response (3.7% in each group) None achieved a good response according to EULAR response criteria. | Minor adverse reactions more common in the dose escalation group (39 vs. 29) One patient in each group had a severe adverse reaction. | |
Luis, 1999 [40] | A: Oral low dose MTX weekly (mean MTX dose 7.0 mg); B: Oral low dose MTX every-other-weekly (mean MTX dose 7.01 mg) | 24 | No significant statistical differences for: joint counts, Ritchie Articular Index, HAQ score, duration of morning stiffness, pain by VAS, or patients’ and physicians’ global health assessments. (p value not reported) | A statistically significantly lower laboratory value for AST (p = 0,041) and ALT (p = 0.006) in the every-other-weekly MTX group. No significant statistical differences for adverse events incidence at 6 months | |
Comparing different routes of administration for MTX after initial failure to 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 | A significantly higher response rates in SC MTX for: ACR20 (78% vs. 70%, p < 0.05) ACR70 (41% vs. 33%, p < 0.05) Number of swollen joints ((2 versus 3; p = 0.04) | No significant differences in adverse events incidence | |
Islam, 2013 [32] | A: Oral MTX; B: SC MTX | 24 | Statistically significantly higher response rates in SC MTX group for: ACR20 (93% vs. 80%, p = 0.02) ACR50 (89% vs. 72%, p = 0.03) No statistically significant differences for ACR70 response (11% vs. 9%, p = 0.72) | Adverse effects relatively less in subcutaneous MTX (p value not reported) | |
Lambert, 2004 [39] | A: Oral MTX to IM 15 mg/week for 6 weeks, then: MTX IM + 5 mg/4 weeks up to 45 mg (escalation group); B: Oral MTX to IM 15 mg/week for 6 weeks, then: IM MTX 15 mg/week (control group) | 22 | No significant differences for: Change in DAS28 (-0.7 ± 1.3 vs. -0.5 ± 1.0, p < 0.1) Individual components of the ACR core disease activity set the DAS28, No differences for: DAS28 < 3.2 (3.7% in each group). | Minor adverse reactions more common in the dose escalation group No significant differences for incidence of serious adverse events (1 patient in each group) | |
A: Oral MTX (10,15,20 and 25 mg/week); B: SC MTX into the abdomen; (10,15,20 and 25 mg/week); C: SC MTX into the thigh (10,15,20 and 25 mg/week) | 8 | Mean concentration of MTX after 4 h higher for SC MTX for all dose levels (most apparent at doses of 15–25 mg) | More adverse events incidence in SC MTX group (2 vs. 0 cases) | ||