Methotrexate for rheumatoid arthritis
Methotrexate is the drug of first choice for most patients with RAAustralia & New Zealand Musculoskeletal Clinical Trials Network (ANZMUSC), 2022. It may be used as monotherapy, or in combination with systemic corticosteroids, or in combination with other csDMARDs, such as leflunomide, sulfasalazine and hydroxychloroquine. If methotrexate is contraindicated or not tolerated, leflunomide is often substituted.
Combination therapy is usually used for patients with active disease or if indicators of poor prognosis are present. First-line ‘triple therapy’ (methotrexate, sulfasalazine and hydroxychloroquine) has been shown to be superior to monotherapy with methotrexateSmolen, 2020.
For most patients with RA, the usual dosage of methotrexate is 20 mg per week, but a dose range exists for different individuals; useLopez-Olivo, 2014:
1methotrexate 10 to 25 mg orally, on one specified day once weekly methotrexate methotrexate methotrexate
OR
1methotrexate 10 to 25 mg subcutaneously, on one specified day once weekly methotrexate methotrexate methotrexate
PLUS with either of the above
folic acid 5 to 10 mg orally, weekly (not on the same day as methotrexate). folic acid folic acid folic acid
The oral bioavailability of methotrexate plateaus above doses of 15 mg. If doses of more than 15 mg orally are ineffective, or if the drug is not tolerated, consider subcutaneous administration. Advice about oral and parenteral administration of methotrexate for RA is available from An Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis: Subcutaneous/intramuscular methotrexate versus oral methotrexate for people with rheumatoid arthritis1Australia & New Zealand Musculoskeletal Clinical Trials Network (ANZMUSC), 2023.
For additional considerations specific to methotrexate use, see Specific consideration fo use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).