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Methotrexate not working so what next?

Hi everyone as the title says my Methotrexate meds don't seem to be working. I currently take 6 tablets a week and I started taking them in February this year . I am still in a lot of pain I have immense fatigue and feel miserable. I am living off pain killers. Even the steroid injection only worked for a week.

Has anyone been through the same as me, and find that the meds simply haven't worked so you have to simply start again.

Any advice very welcome. I have called my nurse specialist but she hasn't got back yet. What do you think she will suggest now?

Thanks everyone.


19 Replies

Hi--- sorry you feeling so bad at the moment. I started taking mthx in October last year and expected results quite quickly. It was at least 3 months before I noticed any difference and am noticing a huge difference now. Hang in there- it's very early days x


I'm afraid Jacki08 is right it's early days and these meds take time. I started MTX in September along with naproxen and gradually built up to 8 tablets (20mg) a week by the end of December. Things have been in their stride since mid February and now it's looking good regarding fatigue, swelling and pain (though I only ever had a little pain compared to what others have described).

A lot of us here have also changed our diets to a 'cleaner' diet with less refined sugars and processed foods in it to help our bodies cope better with this condition. If you look in past posts your find quite a lot of discussions around diets, supplements and other stuff which is interesting and may be helpful for you.

I hope things start turning around for you soon.

All the best



Hi ya,

I remember the frustration at the beginning, they started me on 8 tablets, didn't do much for 4 months so upped me to 10, after another 3-4 months it did start to help (watch out for mouth ulcers, mine were horrendous, needed 6 x folic acid tablets a week to keep them at bay). The hardest thing is the waiting. All I can suggest is surround yourself with super, helpers and people to make you smile, expect it to be s long haul and it does help.

In found family helpful but sometimes whose because every bodies first thing to say was "how b are you feeling? Are the tablets working?" Which made it worse for me. In the end I explained to everybody it was going to take at least 6 months to get anywhere and please stop asking.

You will get there, feel better and get back on with life. Never underestimate the impact on your mental health. I felt a lot of frustration not being right for my young children (aged 1&3 at the time) which really did affect my pain and fatigue, so if your team has access to counselling I really recommend it. It's s marathon not a sprint this illness so all the chopping strategies and tools you can get will only help you through.

Good luck and wish you well x

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Hi, if you started to take them in February then I'd say it's still early day's. Not what you probably want to hear, but true. If you research Mtx you'll find it often says between 6 and 18 wks for it to be noticed. Still ring the Rhuemy helpline but don't be surprised if you are told to give it a bit more time. They may suggest increasing the dose a little too as 8 tablets isn't a huge amount. Paracetamol is good for pain relief and easy on the tummy. Good luck and let me know how you get on.


Hiya, I am slightly ahead of you as I was diagnosed last Sept & like you was started off on methotrexate & a steroid injection. Methotrexate did nothing for me, but you have to give it the full 3 months before you can be sure. Come to that the steroid injection did nothing either. My follow up appointment was with the nurse after taking methotrexate for 3 months & she went back to talk to the consultant when he got back from his holiday, (after I had emailed to subtly remind her). I then had no DMARDs for 3 months as the methotrexate gave me loads of side effects, particularly with my stomach. I hated doing that, but the consultant was right. It took most of that 3 months for my stomach to return to normal, & before then we would not have been able to tell if anything was a hang over from methotrexate or a new drug. [One of the methotrexate side effects was not being able to tolerate a drug that I had taken for years before with no problem]. I then had steroid tablets for 2 weeks, which did work, & I am now on Sulfasalazine - hooray, hooray, hooray, that works. The joint pain & stiffness has stopped progressing - just goes round & round at the same level - & the fatigue is definitely less. And no side effects - just a bit of tummy rumbling at the start. I feel lucky as it's only the second DMARD I've tried. Next step for me is trying to get hold of the Rheumy nurse & see if I can increase the dose to see if we can make the RA lessen, rather than wait for my next appointment which is still 4 months away. I'm afraid it's a long haul with no quick fix. But at least nowadaays there are lots of different fixes to try & find which is right for you. Keep phoning, RAinK


If you can take Sulfasalizine you are very blessed. I lost 13 pounds in 8 weeks. I had no appetite. It took every ounce of energy I had not to mention the diarrhea. The methotrexate isn’t doing anything for me. They have to start you out on the crappiest drugs because insurance doesn’t want to pay for the good ones. I have Psoriatic Arthritis. It not only affects my joints but every single ligament and tendon in my body as well.



like the others say, it takes time. If that dose of MTX really doesn't do it for you there are lots of options that the Rheumatology team can consider. There's room to increase the dose or they might decide to add another drug or two or try something completely different.

The steroid depot injection is just a stop gap measure - they should have explained to you that it would wear off.

The waiting game is very frustrating but you will feel better once they have found the right dose/combination for you.


The guidelines tend to be that you need to try a drug for 6 months before deciding if it has failed. Obviously if you have bad side effects then you stop sooner/immediately, but otherwise it can take that long to be sure. There are many other drugs, but MTX can be the most effective of all of them so it's often considered the best one. Also, if you started at a lower dose and then worked your way up then it really is early days as you need to get to 10mg or so before it has any effect.

It's frustrating, but don't give up hope that it'll work. I felt the same for ages after I started taking it and then one morning I woke up with NO pain - it was brilliant!


Hiya, sorry to hear you are not feeling any benefit from yr meds yet, but im sure others will tell you its still early days yet as you only started them in february, its needs a lil bit more time to build up and get working yet..x


Hi so sorry to hear your pain :( this happened to me 2 yrs ago in the end because nothing was working I was put on Bio drugs, and I've been a lot better, sometimes get mild flares and stiff but nothing compared to what pain I was suffering !! So now inject with Enbrel it suits me + I take Sulfazalazine hope this is helpful and I'm sure your nurse will soon have you sorted, take care xx


You need to keep nagging them for a response, I'm afraid. They are so overwhelmed that it is only those who persist who get attention.


You've received solid advice from everyone but I would question if you've still not been prescribed an NSAID? It's often the case that whilst waiting for a new DMARD to work an NSAID will be prescribed to help towards reducing the inflammation & in turn the pain. I've mentioned before in another reply when I was first diagnosed I had two types of NSAIDS, one to take daily & another to take as required plus a short course of steroids to help ease the inflammation in order to give the DMARD the best chance to start tackling the disease itself.

We can't second guess what your Rheumy nurse will suggest next but I would think she'd like you to persevere a little longer or another increase could be suggested, there's room to increase from 15mg though if it was me I'd be questioning whether I needed something else adding to help the MTX work. I've had RD 7 years & been taking MTX for 6 & always had an NSAID as part of my arsenal.

How often do you take folic acid? If you're not replacing enough of what is lost (MTX is an antimetabolite) that could be adding to your fatigue, so if you're only taking say 2 x 5mg a week you may benefit from an increase. Do you hold your own drug monitoring book, for when you have your bloods taken or maybe you have printouts of your blood test results? If so compare your initial results from the first test taken to the most recent & see if your ESR/CRP level is decreasing. If so this would indicate that the MTX is working even if you don't feel as though it is.

I hope the information you've received helps & gives some hope. We all remember how it is at the start of treatment & waiting for the meds to work, it seems an age. x


Hi I started on methotrexate end Nov and also had a steroid injection which lasted a weekend! A desperate phone call to my consultant's secretary resulted in being prescribed prednisolone to take for 10 weeks until methotrexate kicked in. I started on 30mg prednisolone and what a difference!! I would certainly ask for tablet form as my consultant did say that for some people the steroid injections are very short lasting. I only came off them about a month ago as I did still need at least one a day until then. I started on 10mg methotrexate and am now on 20mg. I have my

Fingers crossed that it is now finally working but am now suffering from lots of fungal rashes , lovely!,! This can be an issue with people on immune suppressing medication,, so "Dr Google" advises. Best wishes and ask for steroid tablets until the methotrexate is effective.



Its like im reading about myself!!!

Im not sure but i think now its even the worst period of my RA. Pain its so strong and im all the time on pain killers and even i was month on sick note from work first time since i get year ago this but nothing change.

RA its going deeper my neck and my muscles are same like other all joints.. So as depression so will see what my super extra dr will say - i dont even remmember how he is looking becouse i have seen him only once on December and he was not even sure what happened to me..



Thank you everyone who replied to my question. Some sound advice from you all. I will persevere with my meds and see how I go .

It's a comfort to know that we have very lovely people on this site in our times of need.

Thank you 😁😁


Hi - I have just had the same problem and my consultant has recommended that the next step is to take methotrexate via injection; and if this doesn't work after 6 months he is going to try another drug (which I can't remember the name of) will find out and post.


Hi, I'm so sorry to hear about your pain. My specialist told me at the start of my MTX treatment that I had to be patient, as the meds take time to have an effect. He also recommended folic acid tablets six times a week, on days that I don't take MTX. After what seemed like a long waiting period, I am now comparatively comfortable. The pains and stiffness do start up from time to time, but I've learnt to take this in my stride.

Patience and best of luck. XX

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Thanks Buddie.

Patience isn't my best thing . I guess I will have to start learning .

Thanks x


that was one of my first ones I have had that xeljanz both tablets, enbrel, and actemra ivs infusions. Been trying to find something for the last two and half years still looking. My doctor gives me prednisone which is a blessing. I have been looking into cbd oil and found some online that isn't to much so I am going to try that. I also saw where one lady said she drinks four cups of pineapple water a day and she is almost of her meds. I knew pineapple was good for inflamation and pain so I might try that to. Maybe with the cbd oil and the pineapple I can get off prednisone at least.


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