Why increase mtx to "max tolerable" so quickly?

Am I missing something here? If methotrexate takes at least 6 weeks and sometimes months to show it is effective, why is the initial dose (routinely) increased every 2 to 3 weeks to a greater dose?

I am tempted to buck the trend and stay on my initial starting dose (10mg) until 3 months and THEN reassess. I understand "aggressive treatment" concept but maybe there are some people who would be sufficiently treated on a lower dose?

39 Replies

  • Hi. Mtx is pretty toxic and makes your liver work hard trying to get rid of it. In the early stages of treatment it's more about how you're tolerating the drug. They'll increase the dose depending on your bloods results.

  • That is why the Methotrexate tablets I get are at the first dose 7-5 any stronger and it effects my kidneys and lowers my blood count I am allergic to many tablets at the moment it's waiting on hospital decision to see what else can I get to ellimate pain and help with movement

  • 10mg is the starting point for a therapeutic dose. And I guess it's 40+ years of using the drug that leads doctors to reckon that it's most effective above 15/17.5 mg. Some doctors ramp up, and others start high and drop down. Like with folic acid different doctors have slightly different approaches.

    I was advised to go for aggressive treatment so MTX built up to 20mg, + 3g Sulpha, + 400mg Hydroxy quite quickly. And stayed on that until I reached remission/low disease activity. Now I've been able to drop down to 17.5mg MTX and lower doses of the other drugs too. It worked for me so no complaints.

  • Thanks Helix - your answer helps a lot. I guess they really have figured out the most effective dose & I must just trust that the increase is necessary (conquer the fear!)

  • Hello Seneca,

    What I have understood is that a higher dose at start is a good thing and does not cause more toxity than a lower starting dose but is more efficient. I have also understood that it usually takes about three months to kick in and if there is no change it's probably not working. There is actually a test that can check if it has been working. You could also try to get the subcutaneous version which is more bioviable and with less adverse effects. I can look up the test for you if you don't already know about it.

  • If you don't mind, I'd love to see that test. Where can I find it?


  • Thank you

  • That's very interesting. Thanks Simba.

  • HI, is this test something that a patient can ask for on the NHS? It looks like an American private test? I am curious as have been told I may have a type of RA which is more resistant to treatment so this sort of test would help and avoid unnecessary trying for months on MTX if it's not going to work

  • I can't see it listed on labtestsonline.uk so also wondered whether this is an American thing?

  • This is the labtestsonline.org.uk link for the MTXP blood test Simba labtestsonline.org.uk/under...

    As I understand it it's normally only used for high dose MTX though, rarely low dose.

  • May be that this is something used in the US. The study that I actually was referring to ( and couldn't find) was explicitly talking about mtx-polyglutamate testing for RA patients after 3 months of unresponsive treatment to avoid further over medication, incase of mtx not being suitable or help in finding the right dose.

  • They will start with a low dose then increase once they can see you tolerate the drug. Also the goal is to achieve remission as quickly as possible. If you are tolerating it well but symptoms not yet under control they will increase the dose, not wait. Hope this makes sense to you lol

  • Thanks Damaged - I know that makes sense. I just think that sometimes they don't wait to see if the low dose is getting symptoms under control before increasing it.

  • That dosnt alway work If they start you on the higher dose and your liver or kidneys start giving you unnecessary problems what's going to be the solution then you will have damaged your organs if you have to come of the RA drug your pain will be worse a small does to start with then increase if your blood and organs are accepting the RA drug

  • So disease activity is the signal for docs to increase methotrexate? That would seem to make sense but my rheumatologist started me on 15mg and then moved me to 20mg at next 4 monthly app despite the fact that my RD seemed to be quiescent with very low inflammation levels. As it happened, 20mg resulted in nasty side effects so was advised to drop down to 17.5 where I am. now. At my last app in March she talked a lot about moving me on to injections so I could possibly tolerate a higher dose even though I have been lucky enough to have very little disease activity since diagnosis and my bloods are fine. Any ideas why rheumy is so keen to put dose up? I keep worrying that there is damage being done by the disease with no symptoms.

  • There seems to be different opinions on what is the optimal dose. Many advocate that it is very individual and if the low dose is working it should not be increased before signs of increase in disease activity. The low dose that seems to work for many is 10mg per week and adding a low dose of pred first instead of increasing the mtx dose is also seen as an alternative..So it is very individual how you react and over or under medication seems to be a common phenomenon 😕

  • Thanks. I was on prednisolene (decreasing dosage) for 9 months when first diagnosed and prescribed mtx but had no problems with the decrease. At moment I think I'm happy to stay on 17.5 mtx rather than inc dose unnecessarily. Thanks again. 👌

  • This is exactly my question, Bookworm. Why keep upping the mtx if no increase in disease activity/blood markers? I don't like the push to take the highest possible dose - its such a scary medication. I'm glad you were able to decrease the mtx and are stable at 17.5mg. Best wishes

  • My consultant said that my Mtx dose (by injection) should be increased from 15mg to 20mg. So I saw my GP to get the prescription approved and he said he wasn't happy to approve it because it was taken subcutaneously (ie more effective). Back to consultant, who wasn't pleased that the GP was overruling a specialist and has again recommended the increase, but this time to 20-22.5mg. It's difficult to know what to do as I am concerned about lung and bone marrow damage, even if at 15mg my liver results seem okay. But of course I need to remember the damage being caused by the underlying inflammation. Sigh....!!

  • Hi ranne21 - did your consultant say why the mtx should be increased? Were there signs of increased or unresolved inflammation even though your bloods were OK? Sometimes it feels like they want to see at what level you DO have bad side effects and then they reduce the dose a bit. But the less I have to gamble with mtx the better, if you ask me!

  • I agree. The consultant thinks my condition is 'not as well controlled as it could be' on the basis of blood tests (but no recent scans to check progression) hence the recommendation, but I'm not sure I'd want to go beyond 17.5mg at the moment. I asked about invisible damage (eg lungs) but the he waived that aside on the basis that I currently have no breathlessness....!?

  • Having said that, I'm seronegative with low CRP but showing anaemia and low haemoglobin.

  • The anemia and low hemoglobin may be cause by MTX. Increasing it would seem the last thing to do ? It is all very confusing. I do not want to be a trouble maker but let's face it , we must be involved in all aspects of our own health care. I no longer remain passive with any doctor. They are human and prone to error.

    Just this past few weeks my GP prescribe amytriptaline . This despite my being very clear about NO mood altering or psychotropic drugs. I did not take them , fortunately. The same week my dentist discovered abscesses in eye tooth. He prescribed Clindamycin , which cannot be taken with Amatriptqline. I developed hives from antibiotic but may have assumed the other drug was cause. Next I developed UTI (e coli). CI pro also cannot be combined with Amitriolaline.

    The point is simply this. It is your body and you are responsible for what goes in it. Doctors make mistakes, have egos , are not created equal. There are excellent doctors but many who are not so great. In my case, as many of you know, drugs are a problem. I have learned to trust myself to know what is best for me. Ultimately, it is the only thing we still control.

  • That is what I say you have got to speak up and question the RA Dr if he is going to prescribe any additional tablets as long as you can manage to keep the pain at a lot you can live with keep it at that I've seen woman landing up on wheelchairs them on higher doses it can only effect your other organs keep moving don't sit too long as you will stiffen up

  • That is why I have been taken off the tablet and it's only 7-5 my blood levels are very low I may need to get a blood transfusion it's quite worrying. I live myself and I am 86 it's more the falling in the house I'm more fighters off I will struggled to get on my feet I have a buzzer for help if need be and have good neighbours though some are older than me I hope you get help

  • Hmmm - I suppose that's the reason (not-improved-enough-blood) but I wish they'd explain in more detail. Also, I wish we could have chest tests every now and again. The lungs thing is my biggest worry!

  • It's a cost/benefit thing isn't it. Surely the Mtx risks increase as the dose is increased, although of course the dose can always be reduced again as appropriate. Mind you, clinic visits are few and far between.

    It'll be interesting to see what the GP says when I see him again.

  • I was started on 7.5 with the intention of increasing to 17.5 over the next few weeks. As it happened every time I tried to move to 10mg my neutrophils dropped so I had to revert to the lower dose. After 3 attempts my rheumy decided to leave me on the low dose and see what happened(I was also on hydroxyl). Even at the low dose I have been in remission for the last 3 years. I am very glad I was able to stay at the low dose, with no nasty side effects.


  • Wow. That is really encouraging SueB. I'm so happy to hear that at least some people manage to control RA at a low dose. Wishing you all the best

  • Hi this is very confusing. I was ramped up from 15 to 25 mg over just 3 weeks, now been changed to injections (as had bad side effects) so back down to 15mg on basis subcut has more direct effect - however was told if I tolerate it for 4 weeks they will increase up again. Isn't there some kind of standard?

  • Exactly - very confusing. 15 to 25mg seems like a big increase over a short period of time - sorry you had a bad time with it.

  • Well people who are unfortunate to need it for cancer take 35mg daily for 7 day periods......so my 17.5mg weekly feels relatively modest!

  • I think many docs are of the opinion that high and aggressive in the beginning gets you into remission qucker, but then again other studies do support a more individualistic approach and believe there is a sweet spot that works best it may be higher or lower depending on the patient. Since the docs really don't know I think we as patients need to follow how we feel and insist that the docs take this seriously and explain thoroughly why a certain dosage regime is recommended in your perticular case.

  • Helixhelix did you start taking all 3 at the same time? OH is on methotrexate (6 months) and hydroxychloroquine (1 month) now but still isn't there - I'm wondering when / if sulfa might be added?

  • I started with MTX, slowly increasing dose up to 20mg (I can't tolerate more than that). Then hydroxy was added in, which helped a bit more but still not completely controlled. So then a few months later Sulpha was added in and again dose slowly increased up to 3mg. And then bingo! RA controlled.

    All in all it was about a year. And then another year while I was still improving, and finally got to low disease activity/remission. And the last 4 years have generally been ok. So keep hoping, it does take time!

  • Ive had my MTX increased from 15mg to 20mg and have now been told by nurse i should have bloods taken once every two months as apposed to one month when i was on lower dose. I asked her why this was and she says this is the way we monitor now.

  • The frequency of monitoring is also about how long you've been on the drug, not just the dose. I now only have blood tests every three months.

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