Brilliant Board Review & CME

🎙️ Episode 25: Methotrexate for OA Pain? Believe It or Not

• Season 1 • Episode 25

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🧠 Surprising contender:

OA is not just wear-and-tear — there's an inflammatory phenotype.

🧪 Trial:

MTX 10–25 mg/week in knee OA with persistent pain.

Significant ↓ pain and improved function vs placebo.

⚠️ Side Effects:

GI upset, mouth ulcers, fatigue.

Hepatotoxicity, myelosuppression, pulmonary fibrosis (rare).

Always co-prescribe folic acid.

🧩 Clinical Takeaway:

Consider in refractory OA when NSAIDs, injections, and PT have failed.

Especially useful when opioids are not an option.

Speaker 1:

now let's talk about pain reduction using methotrexate in osteoarthritis and you're like what? That doesn't make sense. Well, I know your textbook tells you otherwise, but osteoarthritis has an inflammatory component. This has been noted for years. The textbooks haven't caught on and it's a chronic pain that reduces quality of life. I don't know if you've had a loved one, patients, somebody down the street, whatever Yourself is, if you're not moving and you're just kind of stuck and it causes you to have pain to move. Just think about your quality of life. Think about just doing basic things grocery shopping. Maybe you like hiking and you can't hike anymore. Maybe you want to do just simple things going up the stairs in your house and the pain is so much that you cannot do these things. So this is a study. It's a multi-center, randomized, double-blinded, placebo-controlled trial, nice this is in the UK and it's between June 2014 and August 2017. And the patients had to have radiographic osteoarthritis and knee pain within the last three months, with inadequate and knee pain for at least three months, an inadequate response to current medication. They were given methotrexate once weekly and it was started at 10 and titrated up to 25 milligram dose versus placebo, and there was significant reduction in pain in the scores, in the pain scores. So this may be something we're looking at, because when you're treating osteoarthritis, what are you going to get? Usually the patients are older. You can't bang away NSAIDs on them because you're going to have GI bleeds and the side effects of the NSAIDs kidney failure and those kinds of things. You also acetaminophen has been proven to be worthless for osteoarthritis. And then what are you going to use Opioids, and then you have the side effects of opioids. So this may be an answer.

Speaker 1:

Now, methotrexate is not perfect. Remember this is a chemotherapy medication. In fact it's one of the first chemotherapy medications. So GIs can nausea and vomiting about 20 to 65% of the patients Mouth ulcers and sores. People get headaches, fatigue, and you call this methotrexate fog is they kind of feel blah the day after taking one of those pills and you go blah, blah. So what can you do to help? Folic acid, one milligram daily, or you can do five milligrams once a week. Folic acid is cheap. No, methotrexate is cheap.

Speaker 1:

Now, liver damage. Now this can be anything from fibrosis to liver, but more than likely it's just elevation and liver tests and this can happen. Anywhere from 15% to 50% of the patients Now there is inflammation can have inflammation and fibrosis of the lungs. In fact, whenever somebody comes into a pulmonary clinic and there's fibrosis, if they look for methotrexate they're going to blame it on that right away. There also also kind of drops in the WBCs and platelets in a patient. So this is maybe a start to look at of what we can do differently for osteoarthritis, because right now our treatments suck, our medical treatments suck and getting a knee replacement sometimes is not a viable option in patients because it's a pretty rough surgery to come back from. The orthopods do a great job of putting those knees in. It's the recovery and the risk of clots, both DVTs and PEs in that recovery process. So there's a lot of things that we need to do to get better at knee osteoarthritis. Maybe this is a start.