From the Guidelines
Methotrexate (MTX) is the first line treatment for Rheumatoid Arthritis (RA).
Key Points
- The American College of Rheumatology and European League Against Rheumatism (EULAR) recommend MTX as the initial disease-modifying antirheumatic drug (DMARD) for most patients with RA 1.
- MTX should be started as soon as the diagnosis of RA is made, with a target dose of 25 mg/week, and can be combined with short-term glucocorticoids (GCs) to achieve rapid improvement 1.
- The optimal dosage and route of administration of MTX in RA is starting with 15 mg/week orally, escalating with 5 mg/month to 25–30 mg/week, or the highest tolerable dose, with a subsequent switch to subcutaneous administration in case of insufficient response 1.
- MTX has an extensive safety record, well-documented clinical efficacy, and is a cost-effective treatment option for RA 1.
- If MTX is contraindicated or not tolerated, other synthetic DMARDs such as leflunomide, sulfasalazine, or injectable gold can be considered as alternative first-line treatments 1.
- Biological DMARDs, such as tumor necrosis factor (TNF) inhibitors, can be added to MTX if the treatment target is not achieved with MTX alone, especially in patients with poor prognostic factors 1.
From the Research
First Line Treatment for Rheumatoid Arthritis (RA)
- Methotrexate (MTX) is considered the anchor drug among disease-modifying antirheumatic agents and is widely accepted as the first line treatment in the management of RA 2, 3, 4, 5, 6.
- MTX is effective in relieving pain, reducing the number of affected joints, and providing functional improvement in patients with RA 4.
- The use of MTX in combination with other disease-modifying antirheumatic drugs (DMARDs) may be used initially or in a step-up strategy after MTX monotherapy in patients with persistently active disease on monotherapy 2.
- MTX is generally well-tolerated, but has important potential side-effects including a risk of liver toxicity and cytopenias 6.
Mechanism of Action of Methotrexate
- The mechanism of action of MTX in RA is not fully understood, but multiple mechanisms potentially contribute to its anti-inflammatory actions, including the inhibition of purine and pyrimidine synthesis, transmethylation reactions, and promotion of adenosine release 3, 5.
- Adenosine signaling is probably the most widely accepted explanation for the MTX mechanism in RA, given that MTX increases adenosine levels and promotes an overall anti-inflammatory state 3.