Methotrexate does it really work?

Hello all,

It’s been a while. I’ve been busy with work and home life, I am sure it’s much the same for most of you.

I was put on methotrexate initially 15 mgs with 5 mgs folic acid on day after. It didn’t help with the pain, I only suffered the side effects, mouth ulcers, exhaustion and night nausea. Went back to the rheumatology clinic the methotrexate was increased to 25 mgs with folic acid for 6 days of the week excluding the day I take the methotrexate. Last night was the second time I have taken the 25 mgs and still no pain relief, but nausea and exhaustion is still occurring, I can barely move this morning. I feel like I have been run over by a tractor. I have an appointment with the rheumatologist just before Xmas, but I feel I should see him sooner as all I am getting is just complications added to an already complex diagnosis.

What I really what to know is people’s experience of methotrexate and what’s next if this treatment fail. A colleague of mine who has RA has mentioned biologics and so did my rheumatologist at my last visit. I have read up on it but I am still not entirely sure.

What’s been your experience?

Thanks, Nicole

Loads of people do say it really does work but that it can take its time to work as in months and more than three months.

Loads more people use it in addition to things like Humira and Embrel (the first stage ‘biologics’ for the want of a better phrase) as it can help them to be even more effective. And loads of people use it combined with other DMARDS like sulfasalazine or leflunomide before they ever start the biologics.

For me - it just hated me. I tried it first in tablet form and then tried it again a year later by injection. It’s said doing it by injections lessens many of the side effects too so maybe that’s an option for you? Can you call a nurse advice line to discuss? And what other pain relief are you being prescribed in addition to the mxt? I was told given its long lead in time to get effective that I also needed prednisone and anti-inflammatories plus tramadol.

I was also told I had to ‘fail’ two DMARDS before biologics would be considered. And I’m not failing sulfasalazine yet at all as it’s doing some good, more than some good finally after 5 months and with none of the issues I suffered whilst trying mxt. As you’ll gather each of us reacts differently to the various drug options and what works for one doesn’t necessarily work for another. So do take heart as it sounds like you’re just starting to try all the various meds which means you still have a load of options to try. However it also sounds like you might need to up the pain relief in the meantime. :confused:

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I have been on the methotrexate now for nearly 4 months. I also take hydroxychloroquine (I’ve been on this for just over 2 years), Cocodamol, Naproxen, Pregablin and Nortriptylline all for pain. There are some added drugs for back spasms. Unfortunately, I am allergic to sulfalazine.
I know this journey is different for everyone but sometimes hearing that someone else who has been through a similar ordeal makes you know that it’s not just in your head.

Did the biologics work for you?


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You are getting closer. There is a reason you and many others are still on NSAIDs and MTX (or other DMARDS) while they close in on “the right” combination. Its because these meds do work in some measure for most people. They may not work as well as one would hope but so long as there is SOME change based on examination (not just the always subjective reporting of the patient) They will keep them The process is called selection. For a real simplified explanation:

How many rolls of six dice does it take to get six sixes?

Statistically, the chance for it to happen is 1/46,656 – one roll, out of 46,656 on average is six sixes. But I can do it consistently it in seven rolls.

So how how does that happen that happen? Selection. I simply keep the sixes, and reroll the rest. That’s the power of selection. each additional “roll” brings one closer to the desired result…


Hi Nicole.

I think it’s very positive that your rheumy has broached the subject of biologics, it’s good to know that he is considering this option.

My experience of Methotrexate is that it did help considerably but not enough. I also found that upping the dosage really did make a difference. However it’s a slow drug in so many ways so I doubt you’ll know whether the 25 mg makes a difference for a little while yet.

Do you get nausea and exhaustion only (I know, ‘only’ doesn’t seem the right word!) on the day after taking it, or are either or both those things longer lasting? I take Mtx to prop up Humira (a biologic) and strangely, despite being particularly well recently for the longest time ever, I’ve started experiencing a one day ‘Mtx hangover’ for the first time in over 5 years of taking the drug! I think it could be that previously I couldn’t really tell the difference between the yucky Mtx feeling and the frequent yucky PsA feeling! Certainly exhaustion can be a symptom of PsA, possibly some mild nausea too.

Managing the disease through lifestyle definitely helps with PsA symptoms. Possibly it helps with drug tolerance, though I’m on less firm ground there. If you can keep moving - walking, swimming, yoga, tai chi … anything - you may find that fatigue improves over time. Forgive me if I’m preaching to the converted! Drinking a lot of water regularly is also essential when taking Mtx.

Humira has made a huge difference to me. I started it two years after diagnosis and fairly quickly re-discovered a relatively normal life. There have been ups & downs but basically it’s a game changer. Mtx isn’t so glamorous but it can be very useful if you can tolerate it, best to give the higher dose a chance I think, but to get back to your rheumy if side effects are severe despite your best efforts.

And then, if you get the chance, I’d say go for the bio! Sophisticated drugs - yes. Hard on the body - I think not, usually. There’s some degree of risk attached to almost any drug including aspirin, paracetamol etc. (both can be pretty damn risky if taken to excess) but if a drug makes us more mobile and much happier then that has a positive effect on overall health too.


I think there’s not much of it that is just in our heads. I think it’s just the mother and father of a disease and too idiosyncratic and irrational too much of the time, given the huge range of various positive reactions to the meds we get along with the huge range negative effects. And that goes for just the disease itself as well.

I couldn’t understand at the beginning why each one of us was effectively a guinea pig for each med. I understand it just a little better now but it’s still just hard. I’ve yet to try biologics and I imagine it might be a while yet before I’m offered them, given the sulfasalazine is apparently working.


It’s not just in your head. Period.

That said, it is amazing what your brain can do to help make things feel better (won’t stop progression) if you train it. So whilst it is not the cause, training it to be helpful, is definitely worthwhile (meditation, yoga, whatever works for you individually).

As for MTX, no, it had no effect on me. I struggled for 12 months, first 3 on nothing, then 6 months on MTX and prednisone, then another 3 on MTX, prednisone and plaquenil.

There is a large spectrum on the site, however, from people like me, to those who notice it helps with the bios, to those who have successfully been treated by it as a stand-alone therapy for many years.

It is important to know, though, that it’s action is completely different to the biological meds - if MTX doesn’t work for you, that is no indication that the bios won’t. And in fact, even if one biological in the same class doesn’t work, that doesn’t reduce your chances of a different type, in the same class, working.

Being the guinea pig for months to years whilst you find medication that works is not fun - but if you persist, it is EXTREMELY rare not to find one that does.

It is a really hard road, but keep going :hugs:, almost all of us do find the better path :grinning:


Hi there. Early on when there was no real alternative I used methotrexate. It helped my symptoms but I stopped using it bc of feeling nauseous all the time and the terrible mouth sores. Both pills and injections had the same effect. I just couldn’t function on it and not working full time is not an option.i had to change docs to find someone who would prescribe a biologic. At the time,biologics were still new where I live . I hv a wonderful doc now and I was lucky enough to get enbrel and now Humira. I can’t say enough about these drugs. Simply amazing!!! Hang in there :slight_smile:


Hi Nicole,
Sorry methotrexate isn’t your friend…I live in the U.S. and we don’t necessarily have to fail two DMARDS before we get a biologic. I refused methotrexate and sulfasalazine…but, I was diagnosed for 6 years before I caved and agreed to go on Enbrel. And, that took a LOT of encouragement from my doctor, my family and the moderators here. I’ve nearly got a phobia of meds, but when my symptoms got unbearable I had to do something. I think it was that I had psoriasis so long (nearly 40 years) and diagnosis of PsA for 6 years (with symptoms at least several years before that) that there was no problem getting my insurance to cover the biologic. And, I’m so glad I went on Enbrel…I hope if the methotrexate SEs continue to be so bothersome for you your doctor gets you started on a biologic. There’s a pretty good chance you won’t have any SEs from it.
Good luck, and hang in there!


hi Nicole, I have been on Mtx for seven years now, Initially in tablet form and then by injection. I take 15 mgs. I found it started to work for the pain in my hands after about 3 months, it helped with stiffness and some of the swelling went down also. My rheumy increased the dose to 20mgs but it started to cause nausea which was when I changed from tablets to injections, this helped enormously. I now inject Enbrel as well as I have AS too and my spine is painful and stiffening up. The Enbrel started to work fairly quickly, so if you are put on biologics you may find a big improvement. Everyone is different and what works for some does not work for others. I know the mtx is working as I have had to stop both of them for 3 months as I was ill with a parasite I picked up - cryptosporidium, nasty thing! My hands became very painful and once I resumed the mtx the pain subsided considerably. You may need to try a different dmard, hope you get sorted soon.


Hi there Nicole, how are you going on the Methotrexate now?

Wanted to add my experience with it to date to the others comments :slight_smile:

When I first started on Mtx, and again with each dose increase I had what I called a Mtx hangover the day after I took it… fatigue and a bit rough feeling generally… and ended up with ulcers under my dentures too… somewhere around the 3-4 weeks after each increase these SE’s settled and now I don’t seem to have them at all (currently on 20mgs per week, with folic acid every day (except Mtx day))… I also found taking the Mtx before bed meant I slept through to worst of the SE’s and drinking plenty of water with the Mtx and the next day also seemed to help. Improvement of the minor skin issues has been good, improvement in arthritis symptoms (pain and fatigue) seems minimal at this stage (have been on Mtx for just over a year, but only about 3 months on 20mg), trying to stay positive about what seems to be minimal improvement I do wonder if perhaps the Mtx is at least stopping the joint symptoms from worsening, or slowed down that progression, something I guess I’ll never really know. If your SE’s are not too extreme to cope with I’d suggest you hang in there if you can… if you have concerns about SE’s perhaps a chat to your GP or pharmacist about them might be useful.

Wishing you all the best for some rapid improvement!!!

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Thanks for all your kind words and information. It’s not been a great experience taking the full 25mgs and folic acid every day except for the MTX day. The side effects far outweigh the benefits. If I am honest there seems to be no benefits at all. I am still taking pain killers and NSAIDs to help with the joint pains and stiffness. I should be seeing my rheumatologist after Xmas, but I’ll try to see if I can bring it sooner. As the weeks go by my ability to do things are gradually decreasing. Yesterday I couldn’t open a jar of peanut butter, my fingers and wrist were so painful. This morning I can’t walk down the stairs normally as my knees are in agony. I really am not enjoying this journey I want to stop and get off this ride, but I know I can’t.

What next?

Nicole x

Well, you can get some very ingenious gadgets to help with the jars. I’ve just got two sticky pads, one to put jar on, one to place on the lid so I can open it with the heel / palm of my hand but there are better things.

If Mtx isn’t working you will have done your 3+ months ‘trial’ by now I think? Plus you’re taking, or have taken, hydroxy? If your PsA is moderate to severe and you fail to improve on 2 DMARDs then biologics may be considered. I would recommend getting up to speed on biologics in advance of your appointment. As your rheumy has already mentioned them, they may well be the next step so it’s best to think ahead & be prepared!

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I’m so sorry the MTX doesn’t appear to be working. I must admit I had a similar experience, and I understand it can be really discouraging.

As far as what comes next though -yep - what Sybil said. There Are still a lot more options, and almost certainly you will eventually find something that works.

It is a great idea to research the biologics, or any other DMARDs you haven’t tried yet, so that when you do talk to your Rheumy about a medication switch you feel like you can participate properly in that decision.

One thing from my own experience; I did have a similar decline as you on MTX, couldn’t open jars or bottles, had to start walking sideways down the stairs, it was pretty gutting.

For me though, it seems it was just slowly building inflammation that caused the decline, not severe joint or bone damage. Once I got medication that worked, I could walk up and down those stairs again, and, whilst I admit I love having the jar opener in the draw, I only use it occasionally.

So stay hopeful :grinning:

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I was on methotrexate for a few years. I takes a while to work so i was on other medications to help with the pain until the methotrexate kicked in (I think it took 8 weeks).

I found that if I took my dosage on Friday night after eating a heavy meal I slept through the big part of the side effects. I did have fatigue for the weekend but I would just take it easy and be mostly recovered by Monday for work.

The longer you take it the less side effects you should have. The thing to remember is that the side effects you read about on the internet are for higher dosages used to cancer treatment.

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Thanks all, for your advice, greatly appreciated.

I took my MTX as per usual on Thursday night. Felt like a zoombie on Friday. Like I was having an outer body experience or on a super bad hangover. I felt a bit better on Saturday and again worse for wear on Sunday. I have been having really bad joint pains from my neck all through both my arms to my fingers, they are all stiff and extremely sore to touch. I went to bed in agony last night (and yes, I did have all my meds., including pain killers). I was really unsettled throughout the night and was awoken with chest pains twice. Both lasted a few seconds, but it felt like ages before they wore off. I had another this morning and it too has worn off just leaving me with tightness of my chest, similar to when I am having an asthma attack. I have had chest pain before, about 6 months ago. I had been to my GPs and had an ECG taken, but it was clear. I did try to contact my GP this morning, just to be on the safe side, but I was number 20 in the queue, so I know I wouldn’t get seen today.

On the whole, I feel pretty rough again today and I’m wondering if this is all due to the MTX or a PsA flare-up. I will call the rheumatology clinic and ask for my appointment to be moved forward, but in the meantime I really don’t want to be walking around with chest pains. I’m pretty sure they aren’t cardiac related or that I’m having a stroke. So I am presuming it’s the MTX or PsA to blame.

Does anyone know if having PsA or MTX can cause chest pain?



PsA can cause rib pain Costochronditis (not sure I spelt that right) which can be really painful and indeed make you think you’re having a heart attack. Look it up. I had it on the left side the first time and it came on at night and I was certain it was cardiac issues, which of course I did nothing about at 3am except lie there scared silly. It then shifted to the right side so I thought that’s just silly thinking it was cardiac related and then looked it up and saw this. So I calmed right down and felt it was just PsA related. It did however take some weeks to go and bounced around all over my ribs in the meantime. And it was really, really painful at times.

I’d always advocate if you’re that worried about it - making sure it’s not cardiac related but certainly PsA can give you chest pain. It’s like the bits in between your ribs just get inflammed.

I hope this helps.


PsA frequently does. The first time I had it, it was so sudden and severe, it really felt like people describe a heart attack. At the moment it’s just a bit of a tight chest. It is sometimes referred to as costochondritis.

I’m not aware of MTX causing chest pain, with the possible exception of it being related to a chest infection. As you say, move that Rhuematology appointment forward, but if in the meantime your chest is still bothering you and you are feeling unsure about it, get an appointment with the GP, even if it’s in 3 days time. You can always cancel it if you feel better.

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That’s great to hear that PsA causes chest pain. Now I know I’m not totally crazy with my self-diagnosis. The sharp pain has gone but I’m left with tightness in my chest. I tried calling my GP surgery but I was number 20 in the queue. I just got dressed and walked to the surgery. No appointments left, even after I told the receptionist I was having chest pains. I am now sitting on my staircase at home waiting for a GP to ring me. Fingers crossed it’s some time soon.

N x

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I get a lot of chest pains. Either they’re worse at night or it’s just that’s the quiet time when they’re more noticeable as are darker thoughts! I do really wonder what the hell’s going on sometimes, PsA has such a ‘repertoire’.

My chest / ribcage get more tender as the day goes on, if possible I remove my bra by about 4pm -I wear light, soft ones but they seem to get tighter and more uncomfortable through the day.

Clearly PsA kicks quite a few of us in the chest. But I think you’re wise to check it out. So many of the symptoms of this disease could easily be due to something else and I suppose we shouldn’t mess with chest pain.

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