Table 4 Subgroup of early RA patients: Main findings from included RCT evaluating the optimisation of MTX therapy

Comparing different regimens for increasing oral MTX dosages

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

A trend to higher SDAI criteria in the rapid strategy at 24 weeks (42% vs. 28%, p = 0.1), but not at 48 weeks

No significant differences in adverse events incidence

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

Significant differences in favour of intensive strategy group for:

Sustained remission rate after 1 year (35% vs. 14%, p < 0.001) and 2 years (50% vs. 35%, p = 0.03).

Mean time to sustained remission (10.4 months vs. 14.3 months; p < 0.001)

Median AUC for morning stiffness (17.0 vs. 23.7, p = 0.009); erythrocyte sedimentation rate (ESR) (17.7 vs. 21.6, p = 0.007); tender joint count (3.6 vs. 5.5, p = 0.001); swollen joint count (2.7 vs. 4.7, p = 0.001); VAS general well-being (19.0 vs. 31.2, p = 0.001), and VAS pain (12.0 vs. 19.0, p = 0.001).

No statistical differences for clinical variables (tender joint count, swollen joint count, VAS general well-being, ACR50 and VAS pain) at two years.

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

Significant differences in favour of the SC MTX group for ACR20 response rates as early as week 16 (85% vs. 77%; p < 0.05).

No significant differences in adverse events incidence