What longterm side effects have others had from being on methotrexate?

@salgalincal - I don't have any experience with Methotrexate but there are a lot of discussions by members asking about side effects. Here's a search link that lists the different discussions - https://connect.mayoclinic.org/search/discussions/.

Great question! I started pred end of March, 2025 & it worked immediately (Now at 3/3.5 alternating days) Rheumy started me on methotrexate end of May, 2025. I don’t know of any physical side effects except maybe what’s going on inside my body. My hair thinned, weight gain around my midsection bigly, & dreadful bruising at the slightest bump on forearms/hands. Prednisone? Method?
I did notice in my recent lab work where numbers for kidney functions while in the “normal” range were getting lower, (labs done every 3-4 months) one on the cusp. I brought that up last week to Rheumy who said let’s test in 6 weeks. If I hadn’t mentioned this to him he’d probably not authorized the test. He said oh your labs look good then went quickly on with our short virtual visit. Lucky to get 10-15 min to discuss issues like what’s side effects, biologicals, etc. guess I should be thankful I even have a Rheumy!?

Sometimes we have to be like that door to door salesman in the old movies and cartoons and not let the doctor get out of the door. Specialists are usually overbooked and in a hurry to get to their next patient. As long as you're still talking to them, they can't leave the room. Say anything you need to until you get your thoughts together with your questions. If possible, bring someone else with you to your appointment and tag team your doctor. It can be difficult to think quickly enough with follow up questions after you hear something that interrupts your train of thought.

The pulmonologist said methotrexate caused interstitial lung disease and I have to stop taking it. The rheumatologist said that's nonsense but has taken me off methotrexate regardless. I don't think it's the cause of my lung disease. I think it's due to living in an industrial suburb for three years.

Watch your liver enzymes. I went from fatty liver to borderline cirrhosis. Fortunately, I was able to reverse it by stopping methotrexate and following a strict diet - no fried or processed foods, red meat, alcohol and limited dairy. I had a prescription for Rezdiffra but couldn't afford the $1000 Medicare copay. Good luck. You can do it.

I’ve been on long-term methotrexate as well (different autoimmune condition), so I can share what tends to come up. First off, the fact that you’ve tolerated 20mg weekly for 3 years with only mild hair thinning is actually a pretty good sign. A lot of people who struggle long-term usually have issues much earlier. From what I’ve seen (and experienced), the main long-term things doctors monitor are:
liver enzyme changes (regular bloodwork is key)
fatigue the day after dosing (“methotrexate hangover”)
hair thinning (often folate-related and dose-sensitive)
mild increase in infection risk
less commonly: mouth sores or nausea if folate isn’t optimized
very rare: lung inflammation, which is why any new persistent cough gets checked
Most people who stay on it for years do so because it keeps things controlled and lets them stay on low or off steroids like prednisone.
For conditions like polymyalgia rheumatica, it’s pretty common to stay on MTX long-term as a steroid-sparing med while tapering prednisone.
Honestly, if you’ve made it this far with stable labs and minimal side effects, you’re probably in the “this is working well” group rather than anything concerning developing later.

Been on MTX for 22+ years for Psoriatic Arthritis. Have had no discernible side effects. With PMR and Prednisone, I feel MTX doesn't help me. Definite side effects with Pred. 15mg weekly MTX, 7mg Pred.