Methotrexate Is Not Recommended for Treating Osteoarthritis
Methotrexate is strongly recommended against for the treatment of osteoarthritis of the knee, hip, and/or hand as well-designed randomized controlled trials have demonstrated no efficacy. 1
Evidence Against Methotrexate Use in Osteoarthritis
The 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis explicitly states that methotrexate is strongly recommended against in patients with knee, hip, and/or hand osteoarthritis 1
This strong recommendation against methotrexate use is based on well-designed randomized controlled trials specifically conducted in patients with erosive hand osteoarthritis that demonstrated no efficacy 1
The guideline prioritizes treatments with proven benefits for reducing pain and improving function while avoiding those without demonstrated efficacy 1
Appropriate First-Line Treatments for Osteoarthritis
Instead of methotrexate, the following treatments are recommended for osteoarthritis:
Non-pharmacological approaches including exercise, weight management, and physical therapy should be considered first-line interventions for all osteoarthritis patients 1
Topical and oral NSAIDs are conditionally recommended for pain management in osteoarthritis when non-pharmacological approaches are insufficient 1
Intra-articular corticosteroid injections may be considered for short-term pain relief in patients with knee or hip osteoarthritis 1
Recent Research on Methotrexate in Osteoarthritis
Despite the strong recommendation against methotrexate in the 2019 guidelines, it's worth noting that more recent research has emerged:
A 2024 randomized, placebo-controlled clinical trial (PROMOTE) showed that oral methotrexate demonstrated a statistically significant reduction in knee osteoarthritis pain, stiffness, and function at 6 months compared to placebo 2
This study found a mean pain reduction of 0.79 points on a numerical rating scale in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030) 2
A smaller 2019 study also reported that methotrexate treatment for moderate to severe knee OA could reduce pain severity and improve functional status and quality of life 3
Clinical Implications and Considerations
Despite these recent positive findings, the current guidelines still strongly recommend against methotrexate use in osteoarthritis based on the totality of evidence available when the guidelines were developed 1
The clinical significance of the pain reduction observed in the PROMOTE trial (0.79 points on a 0-10 scale) may be questioned, as many consider a reduction of at least 2 points or 30% to be clinically meaningful 2
Methotrexate carries potential risks including liver toxicity and cytopenias that must be weighed against any potential benefits 4
Until newer guidelines incorporating these recent studies are published, clinicians should continue to follow the current strong recommendation against methotrexate use for osteoarthritis 1
Contrast with Methotrexate Use in Inflammatory Arthritis
While not recommended for osteoarthritis, methotrexate is considered the anchor drug and first-line treatment for rheumatoid arthritis and other inflammatory arthritides 1
In rheumatoid arthritis, methotrexate has proven clinical and radiological efficacy, a relatively beneficial safety profile, and beneficial properties in treatment combinations 1
For juvenile idiopathic arthritis, methotrexate is also recommended as first-line treatment over other non-biologic DMARDs 1
This contrast highlights the importance of distinguishing between osteoarthritis (primarily a degenerative condition) and inflammatory arthritides when selecting appropriate treatments 1