What is methotrexate?

It is a prescription medicine that calms inflammation and is widely used for rheumatoid arthritis. Researchers have been testing whether it can also ease osteoarthritis pain.

Does methotrexate help knee osteoarthritis pain?

In this review of 3 knee trials with 313 people, it reduced pain at 6 months but not significantly at 3 to 4 months. The evidence is limited, so it is not a routine osteoarthritis treatment.

Should I ask my doctor about methotrexate for knee arthritis?

You can, especially if standard treatments have not helped. It needs a prescription and regular monitoring, so a rheumatologist can tell you whether it makes sense for you.

Research Summary

Can Methotrexate Ease Knee Arthritis Pain? Review of 5 Trials Finds a Modest Benefit at 6 Months

By KneePainNews Editorial Team · October 31, 2026 · Editorial Standards

Not medical advice. This is a plain-English summary for general information. Talk to your doctor or physical therapist before changing your care. Read our medical disclaimer.

Methotrexate, a medicine long used for rheumatoid arthritis, was linked to less knee osteoarthritis pain at 6 months in a new review of randomized trials, though not at the earlier 3 to 4 month mark. The systematic review and meta-analysis was published in Reumatología Clínica.

What was studied

Osteoarthritis is usually thought of as wear-and-tear arthritis, but inflammation in the joint can play a part in pain. Because methotrexate calms inflammation in inflammatory arthritis, researchers have tested whether it could help osteoarthritis pain too. This review gathered the randomized controlled trials on that question.

The authors found 3 trials testing methotrexate for knee pain (313 people) and 2 trials for hand pain (161 people). They checked each trial for risk of bias and pooled the results.

Key findings

For knee osteoarthritis, methotrexate significantly reduced pain at 6 months.
For the knee, the reduction at 3 to 4 months was not statistically significant.
For hand osteoarthritis, methotrexate significantly reduced pain at 3 to 4 months.
Leaving out the trials at high risk of bias did not change whether any result was significant.

What it means for people with knee pain

Methotrexate is not a standard osteoarthritis treatment, and this review does not change that on its own. It suggests the drug may offer some pain relief after several months for some people, but it is a prescription medicine that needs regular monitoring. If your knee pain is not controlled with exercise, weight management and usual medicines, it is a reasonable question to raise with a rheumatologist.

Limitations

Only 5 trials and fewer than 500 people were included, and only 3 trials looked at knees. The confidence range for the 6-month knee result was wide, so the true size of the benefit is uncertain. The abstract does not report side effects, which matter a great deal for this drug.

Source: Ozminkowski E, Ozminkowski S, Bashir H. Methotrexate treatment for pain due to osteoarthritis of the hand and knee: A systematic review and meta analysis. Reumatol Clin (Engl Ed), 2026 Oct;22(8):502248. doi:10.1016/j.reumae.2026.502248. PMID 42963166. Read the original

Frequently asked questions

What is methotrexate?: It is a prescription medicine that calms inflammation and is widely used for rheumatoid arthritis. Researchers have been testing whether it can also ease osteoarthritis pain.
Does methotrexate help knee osteoarthritis pain?: In this review of 3 knee trials with 313 people, it reduced pain at 6 months but not significantly at 3 to 4 months. The evidence is limited, so it is not a routine osteoarthritis treatment.
Should I ask my doctor about methotrexate for knee arthritis?: You can, especially if standard treatments have not helped. It needs a prescription and regular monitoring, so a rheumatologist can tell you whether it makes sense for you.

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