Table 1 Multinational recommendations for the use of methotrexate in RA.

1

The work-up for patients starting methotrexate should include clinical assessment of risk factors for methotrexate toxicity (including alcohol intake), patient education, AST, ALT, albumin, CBC, creatinine, chest × ray (obtained within the previous year); consider serology for HIV, hepatitis B/C, blood fasting glucose, lipid profile and pregnancy test.

4

C

[39, 231–237]

2

Oral methotrexate should be started at 10 to 15 mg/week, with escalation of 5 mg every 2 to 4 weeks up to 20 to 30 mg/week, depending on clinical response and tolerability; parenteral administration should be considered in the case of inadequate clinical response or intolerance.

2b

B

[238–242]

3

Prescription of at least 5 mg folic acid per week with methotrexate therapy is strongly recommended.

1a-

A

[207, 243–245]

4

When starting methotrexate or increasing the dose, ALT with or without AST, creatinine and CBC should be performed every 1 to 1.5 months until a stable dose is reached and every 1 to 3 months thereafter; clinical assessment for side effects and risk factors should be performed at each visit.

4

C

[39, 233, 246–250]

5

Methotrexate should be stopped if there is a confirmed increase in ALT/AST greater than three times the ULN, but may be reinstituted at a lower dose following normalization. If the ALT/AST levels are persistently elevated up to three times the ULN, the dose of methotrexate should be adjusted; diagnostic procedures should be considered in the case of persistently elevated ALT/AST more than three times the ULN after discontinuation.

2b

C

[237, 250–252]

6

Based on its acceptable safety profile, methotrexate is appropriate for long-term use.

2b

B

[253–258]

7

In DMARD-naïve patients the balance of the efficacy/toxicity favors methotrexate monotherapy over combination with other conventional DMARDs; methotrexate should be considered as the anchor for combination therapy when methotrexate monotherapy does not achieve disease control.

1a-

A

[7, 57, 259–263]

8

Methotrexate can be safely continued in the perioperative period in RA patients undergoing elective orthopedic surgery.

1b

B

[264, 265]

9

Methotrexate should not be used for at least three months before planned pregnancy for men and women and should not be used during pregnancy or breast feeding

4

C

[266–268]