From the Guidelines
Methotrexate is not recommended for patients with osteoarthritis (OA) of the knee, hip, and/or hand.
Key Points
- Well-designed RCTs have demonstrated no efficacy of methotrexate in patients with erosive hand OA 1.
- The 2019 American College of Rheumatology guideline strongly recommends against the use of methotrexate in patients with knee, hip, and/or hand OA 1.
- The lack of efficacy of methotrexate in OA is supported by high-quality evidence, making it an unfavorable treatment option for patients with OA.
Treatment Alternatives
- Other treatment options, such as nonpharmacologic therapies, topical and oral NSAIDs, and intraarticular steroids, may be considered for patients with OA.
- Hyaluronic acid injections may be considered in certain cases, but their use is conditionally recommended against due to limited evidence of benefit and potential harm 1.
The FDA Drug Labels for methotrexate (PO) do not address this question.
From the Research
Relationship Between Methotrexate and Osteoarthritis
The relationship between Methotrexate and osteoarthritis has been studied in several clinical trials. The key findings are:
- Methotrexate has been shown to reduce pain and stiffness in patients with knee osteoarthritis 2, 3, 4, 5.
- A randomized, double-blind, placebo-controlled trial found that Methotrexate significantly reduced knee pain, stiffness, and function at 6 months 2.
- A meta-analysis of randomized controlled trials found that Methotrexate improved pain and stiffness in knee osteoarthritis, but had no significant effect on hand osteoarthritis 3.
- Another systematic review and meta-analysis found that Methotrexate significantly reduced knee and hand stiffness, but the current literature may be underpowered and more robust trials are needed to validate these findings 4.
- A randomized clinical trial found that Methotrexate improved pain severity, functional status, and quality of life in patients with moderate to severe knee osteoarthritis 5.
Specific Findings
Some specific findings from the studies include:
- A significant reduction in knee pain of 0.79 points on the numerical rating scale (NRS) in favor of Methotrexate at 6 months 2.
- A significant improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness and function scores at 6 months 2.
- A significant reduction in knee and hand stiffness at the end of follow-up and at 6 months of follow-up 4.
- No significant difference in pain relief between Methotrexate and placebo in patients with hand osteoarthritis 6.
Study Limitations
The studies had some limitations, including: