Recommendation | Level of evidence | Grade of recommendation | Agreement mean (SD) | ||||
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 x ray (obtained within the previous year); consider serology for HIV, hepatitis B/C, blood fasting glucose, lipid profile and pregnancy test. | 4 | C | 8.2 (1.9) | |||
2 | Oral methotrexate should be started at 10–15 mg/week, with escalation of 5 mg every 2–4 weeks up to 20–30 mg/week, depending on clinical response and tolerability; parenteral administration should be considered in the case of inadequate clinical response or intolerance. | 2b | B | 7.8 (2.6) | |||
3 | Prescription of at least 5 mg folic acid per week with methotrexate therapy is strongly recommended. | 1a– | A | 7.5 (2.7) | |||
4 | When starting methotrexate or increasing the dose, ALT with or without AST, creatinine and CBC should be performed every 1–1.5 months until a stable dose is reached and every 1–3 months thereafter; clinical assessment for side effects and risk factors should be performed at each visit. | 4 | C | 8.1 (2.1) | |||
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 normalisation. 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 | 7.4 (2.3) | |||
6 | Based on its acceptable safety profile, methotrexate is appropriate for long-term use. | 2b | B | 8.7 (1.9) | |||
7 | In DMARD-naive patients the balance of the efficacy/toxicity favours methotrexate monotherapy over combination with other conventional DMARD; methotrexate should be considered as the anchor for combination therapy when methotrexate monotherapy does not achieve disease control. | 1a– | A | 8.3 (2.1) | |||
8 | Methotrexate, as a steroid-sparing agent, is recommended in giant-cell arteritis and polymyalgia rheumatica and can be considered in patients with systemic lupus erythematosus or (juvenile) dermatomyositis. | 1b | B | 7.7 (2.1) | |||
9 | Methotrexate can be safely continued in the perioperative period in RA patients undergoing elective orthopaedic surgery. | 1b | B | 8.8 (1.9) | |||
10 | Methotrexate should not be used for at least 3 months before planned pregnancy for men and women and should not be used during pregnancy or breast feeding. | 4 | C | 8.2 (2.7) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC, complete blood count; DMARD, disease-modifying antirheumatic drug; RA, rheumatoid arthritis; ULN, upper limit of normal.