I am new here but have been reading this great forum for a while and found so much knowledge and encouragement from everyone who contributes so it feels like time to say hello. I was diagnosed with RA in March this year and started on MTX. Been on 20mg for about 4 months. Although esr and crp have gone down a lot the pain remains not much changed and is every-day. I am about to start injecting the MTX .
I was wondering whether anyone can explain about Bioavailability. I have read that this varies from about 50-80%. So if you are a 50%er taking 20mg of MTX you only get the effect of 10mg. Would this apply to the side effects and toxicity as well or is it just the effectiveness of the immuno- suppressant part?
Sometimes trying to understand RA makes my head spin but other times it helps a lot to try and thoroughly think about it.
warm wishes to you all...Rosey
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roseyx
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Hiya Rosey, welcome, pleased you've now joined us & that you've found being here helpful. There have been many studies of comparison on this subject, one of the more up to date & comprehensive ones is this link.springer.com/article/1...
Note the drop down boxes following the Abstract, these contain Bioavailability, Efficacy & Tolerability, Conclusion etc.
If there's anything you need clarification on I'll try my best to help, that's if it's not beyond me!
On a personal note I had to change over to subcut when my liver objected to an increase in dose from 15mg to 20mg oral. I started on 15mg which was fine by my liver but didn't control me well enough so it was increased to 20mg which my liver had a benny at so I went down to 17.5mg which at the time was ok for both disease & liver. I've tried 20mg twice but the same happened, liver objected so I've been on 17.5mg plus 2 DMARDs. I've responded negatively to both so I'm relying on MTX & low dose prednisolone, which I had been tapering but this has been halted until my next Rheumy appointment when I'll have a review.
Thanks very much Nomoreheels. That article answered a lot of things I have been wondering and gives me some hope that changing to injections might start to bring improvement. So far MTX has been a disappointment and its hard to keep on taking it when it does'nt appear to be working. It's interesting what you said about 2.5mg dose change having such a critical effect for you.I felt a lot more side effects and generally knocked out after going past 15.
Pleased it helps. Sorry MTX has been a disappointment, although it is showing promise if your inflammatory levels have lowered so I wonder if it needs a little support by the way of an NSAID or pain relief as you still have pain. When I was first diagnosed 9 years ago I was prescribed a DMARD (not MTX, that was my second, I was given hydroxychloroquine) & a couple of NSAIDs, one to take nightly ( the intention being it would help with morning stiffness) & another for when the nightly one wasn't enough. I was also given a short course of steroids though some are given an injection, both intended to reduce inflammation & in turn pain whilst the DMARD had chance to work. You probably know that DMARDs don't work straight away, they can take 12 weeks or more to work although subtle changes are usually noticed before then, your inflammatory levels for instance.
Re your hair, it is a common side effect although more often than not temporary & related to the reduction in folate. This is why you're prescribed folic acid because MTX works by blocking DNA synthesis slowing the growth of not only unwanted cells but also those we need such as DNA cells in the GI tract, hair follicles, skin, liver, brain & other areas. You'll notice they're all related to side effects, this is why we need to supplement with folic acid. As it's not specifically licensed for use with MTX & is thought to reduce the efficacy Rheumy's differ in their thoughts on prescribing. When I first started MTX 8 years ago I was prescribed FA just the day after which was increased to the day before as well when my hair started thinning. My current Rheumy prefers all her MTX patients start on 6, that's 5mg every day except MTX day, she's in the camp that are of the belief that it only reduces the effect if taken on the same day. So, with luck you'll be like most & find your hair settles but if it becomes a real concern do discuss it with your Rheumy. Mine thinned more with my last DMARD, leflunomide, more than it ever did either at the start of MTX or with any increase but it was short lived. To be honest it was only my hairdresser & I who noticed & she just cut it a little shorter & in an easier style so I didn't need to use much product or faff about styling it too much. One thing that I am happy about is that though I have a quite a lot of hair it's fine & ramrod straight but it's grown back with a curl so has lots more body I hardly need do anything with it except wash it & let it dry.
Yes I was ready for waiting but sometimes it feels endless and hope starts to disappear... but thanks for answering my concerns.It really helps and the explanation of Folic Acid is great. I am going to try taking 6 as my GP says take however many you want since there is no consensus on dosage. I don't have much contact with rheumatologist but good doctor on the island where I live.
I wouldn't stop MTX because of hair thinning but it's disturbing.
What about NSAIDS and MTX combination? I was taking diclofenac before starting the MTX but was told not to mix the 2 because of increased toxicity.I also had 2 IM steroid injections early in the year which were wonderful relief. I have been told I can have another this winter so saving it up for a bit as winter has a long way to go.
It must, I understand that, but with your inflammation levels lowering even though you may not notice it helping I would think if it was stopped within a week or so you'd be seeing it was!
Pleased the folic acid explanation helped. So, the DMARD (MTX)/NSAID question. Yes, under normal circumstances the two wouldn't be mixed but sorry to say we're not classed as normal any more! By that I mean exceptional circumstances come into play so if they're indicated we're prescribed them. The concern is they give the kidneys a bashing but we're well monitored, regular drug monitoring blood tests include urea & creatinine so would show & be picked up if they were being affected. Usually unless otherwise indicated one of the COX-1 NSAIDs, naproxen, ibuprofen etc would be prescribed (& co-prescribed a ppi, stomach protector.. omeprazole or similar as they can be hard on the tum particularly when taking them regularly, taking them with or after food helps). If you're at risk of developing ulcers or needing them longer term a COX-2 NSAID would be prescribed, etoricoxib or celecoxib, those I've been prescribed for around 5 years. Obviously the aim of our treatment is to avoid if possible any erosion or damage of the joints, this is caused by inflammation, hence the additional prescribing of an NSAID, which also eases pain so it's use is two-fold. Not only that uncontrolled inflammation can also have an affect on the comorbitidites of RD, we need to protect the heart, lungs plus the nervous system, so the nerves, uncontrolled inflammation compresses the nerves resulting in conditions such as Carpal Tunnel Syndrome, peripheral neuropathy, sciatica etc.
They don't like to give too many steroids, or have us rely on them, because of the adverse effect on bone thinning, skin thinning in the topical forms & at the site of injections, possible hypertension & they can cause blood sugar problems & cause diabetes. Many other things too so usually they try to limit them to 3 general a year & similar for injecting into specific joints. So, yes, try to hold off as long as you can though don't leave it too late because it makes sense if you have more issues the higher the dose they may need to inject, or it may need to work harder so likely to not be as helpful for as long.
Thanks. You are very knowledgeable and generous to take all this time explaining. Is it Ok to continue on this thread with another question. (I have never forumed before) ..
there is one thing I'd like to query. I thought that NSAIDS did not prevent joint damage which was why they are so keen to get the immuno suppressants started ??
I am very reluctant to take any extra drugs if it's at all possible to tough it out with the pain unless there is a very convincing reason to.
It's encouraging what you say about MTX working to some extent and yes there is no way of knowing how much worse it would be if I wasn't taking it but at the start the doctors make it sound almost certain that once the MTX kicks in life will be back to normal. Still.. , I know they want to raise your spirits.
The advantage if you started another thread if you have another question is more people may see it & respond. If it's within an existing thread & the original title or replies don't apply to them it may be skimmed over & missed if it doesn't interest them or they don't think they can add anything constructive.
That said I'm happy to answer your question! No, NSAIDs can't prevent joint damage on their own but they can be helpful as an additional aid to dampening down the inflammation that can contributes to joint damage, not on their own but as part of treatment alongside DMARDs. They are helpful though as the linchpin of Osteoarthritis treatment, there's little else except for pain relief & exercise that's beneficial in easing the symptoms of OA. So, back to RD, NSAIDs are used as an additional med to help in controlling the inflammation that can contribute to joint damage, particularly whilst waiting for DMARDs to reach their potential, the 12 weeks or so they're building up to working, this is why they're so often co-prescribed at the start of treatment. They're also helpful in controlling pain because the inflammation is in the joint, if the NSAID works it allows us to use the joint whereas if we didn't the likelihood would be we wouldn't use it or use it less because of pain & that's not good either. So, if your Rheumy thinks you'd benefit he'll prescribe one. I've just replied on another thread about the last corner of a fitted bed sheet, by the last corner my hand was screaming so had my h do it. Never push a joint to the point of extreme pain, it can't do it any good.
I think Rheumy's tend to work comparatively, they mean compared to not having treatment you'll be normal bycomparison. They're trying to tell you that things will be better than they are now. There are people who go to their diagnostic appointment who probably haven't even heard of RD, or what the future holds, all they know is they're in the most terrible pain which often came on quite suddenly. Those who do have an idea maybe have looked online & frightened themselves half to death by searching on poorly controlled sites giving conflicting info likely spurious at worst.
It's like I said about if you stopped the MTX you'd realise it has been working, however little, you could be feeling a whole lot worse than you could be & yes, you could find out how much worse it would be... by stopping it, but I don't recommend that!
I think it's good to think about it all, as personally I feel the more I understand the better able I am to manage my disease. But as with everything, the more you know the more you realise you have still to grapple with!
Anyway, I think the paper NMH has linked does cover the medical knowledge of this. For me, the switch for tablets to injectable did help side effects. I had developed mouth ulcers which immediately vanished and although I hadn't really suffered the nausea that other mention the vague feeling of queasiness on MTX day also vanished. So it is the reverse, by injecting I was getting the benefit of more of the MTX but instead of feeling more side effects I felt less.....
Thanks very much HH for your reply. Its just as you say...the more you know the deeper you find there is to go. Its also good to hear your experience of side effects with injections. I am almost looking forward to it now..
Hi Rosey
Hoping you get relief soon. We seem to all react differently to various drugs, as seen by previous responses; and my experience is different again!
I have had mouth ulcers, itchy rash that erupts and scabs without me touching it, mood changes, white blood cell counts dropping but not yet a reaction by the liver or a bout of pneumonia..
As I understand it Bioavailability describes how much of the drug your body actually absorbs. When taken orally some is inevitably lost but the figures I have read say there is a variation in absorption rate of between 50-80% ( for oral )
So I just meant by 50%er, someone at the lower end whose dose is effectively being halved.
I wondered if being at that end of it means your body is good at getting rid of toxins?
With injections dose effectiveness is raised by a third on average. So if you began on injections then that was all bypassed anyway.
I hope the leflunomide works for you. I suppose its like starting again with the waiting.
I came over to see your profile, roseyx after that stunner photo I stumbled across.
I just want to say that as I am embarking on my RA journey with meds having toughed it at much as I could without RA drugs, you really helped me understand all this so much better.
First you shared beauty, now knowledge. Thank you, roseyx
Hi Airie, Thanks for such a nice message. I am glad you enjoyed the solstice jellyfish. It was very special to me. I wonder how long you toughed it out for and hope you feel positive about starting the meds. Is it MTX you are taking ? & are you a landscape painter ?
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