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

🧠 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.

Transcript

Speaker 1 0:01

now let's talk about pain reduction using methotrexate in osteoarthritis and you're like what ? That doesn't make sense . Well ,

Methotrexate for Osteoarthritis Pain Reduction

Speaker 1 0:11

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

UK Clinical Trial Results

Speaker 1 0:59

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

Limitations of Current OA Treatments

Speaker 1 1:33

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 1:46

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%

Methotrexate Side Effects

Speaker 1 1:57

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 2:20

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 .

Future of Osteoarthritis Treatment

Speaker 1 3:13

So there's a lot of things that we need to do to get better at knee osteoarthritis . Maybe this is a start .