Recommendation | Level of evidence | Grade of recommendation | Selected references | |
---|---|---|---|---|
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 | |
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 | |
3 | Prescription of at least 5 mg folic acid per week with methotrexate therapy is strongly recommended. | 1a- | A | |
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 | |
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 | |
6 | Based on its acceptable safety profile, methotrexate is appropriate for long-term use. | 2b | B | |
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 | |
8 | Methotrexate can be safely continued in the perioperative period in RA patients undergoing elective orthopedic surgery. | 1b | B | |
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 |