Azathioprine

Bones, joints and muscles
1

Good afternnoon everyone

I wrote before (under the name PatC) under another thread about my experience so far - and thank you for your responses. Like all new members of this forum, it is so great to know I am not alone!

I have now managed to see a Rheum Consultant who confirmed GCA and PMA and had recommended a gentler withdrawl regime from 20mg - 1mg every one or two weeks depending how I feel. He says I could be off steroids alogether in 2 to 3 years. I am very happy with this level of withdrawl as I have been on 20mg for nearly 2 months now but don't want to risk the seroius withdrawl symptons I had last time.

He has also recommended Azathioprine to help steroid reduction but I can only have it \"if my TPMT levels are satisfactory\".

Has anyone had any else had experience of Azathioprine?

2

Hi Patsy Ann,

I googled Azathioprine and it seems a very strong medication with nasty long term side effects. But I don't know enough to comment and wondered if you could say a little bit more about why he is considering it for you. Jill

3

Whoops missed out a couple of sentences. Did you start on 20mg - it seems low for GCA. Perhaps that's in your other thread. What's the title of your other thread? I just googled TPMTs and the chemistry - it's beyond me so I'll just but out now. :oops: Hope you go well with it. Jill

4

Patsy Ann and Jill 48, this site has many drugs listed and you need not 'google them'.

Go to Patient UK Home, it is on the top left hand side of this page and then follow the link.

Alernatively here is the web link https://patient.info/medicine/Azathioprine.htm

As everything on this site is medically checked it is helpful.

5

Hi - I didn't comment earlier as I have no personal experience of azathioprine but I did spend a long time yesterday looking for papers about it. This is what I found:

Like methotrexate and a couple of other drugs it has been used in very small-scale clinical trials to see if it has any value as a \"steroid-sparer\" in long-term steroid treatment in PMR. The general opinion seems to be that it might possibly help but that much larger-scale controlled trials need to be done. One of the other drugs (an anti-TNF substance) had the trial abandoned early as there was a possibility that it was actually detrimental.

The main comment about azathioprine was that the effect takes a long time to appear (at least a year) and, since it is a very powerful drug, should be reserved for elderly patients with a range of other illnesses which make steroid use unadvisable, for example diabetes, osteoporosis and pre-existing heart disease, or for use in cases where a high dose of steroid is needed to control symptoms and which then becomes impossible to reduce to an acceptable low dose. There was also a comment warning that just because something works in this way in other autoimmune diseases it should not be assumed that it will will work in PMR - both because the mechanism of the disease is not yet known and because it is also not entirely clear how these drugs work in some of the other diseases to allow less steroid to be used.

The opinion seems to vary as to what \"low dose\" means but is somewhere between 5 and 10 mg per day. Some doctors are of the opinion that once we are at about 7.5mg per day that is the amount our body produces anyway and so the long-term side-effects should be negligible - others want to get down to 5mg per day. As we know, others want us off steroids altogether irrespective of whether our body and the PMR approves or not!

I did find some work from a group who are asking whether this spectrum of diseases is a manifestation of inadequate adrenal function - which is something I brought up as a possible cause of PMR several months ago in a post. If this is shown to be the case then our steroid treatment is a \"replacement\" treatment, like insulin in diabetes and thyroxine in hypothyroidism. Since we are almost never (as far as I know anyway) investigated for anything in the endocrine diseases spectrum other than thyroid function at a very superficial level to rule that out when we present with PMR symptoms no-one is likely to know about that at present.

Whilst PMR is possibly or even probably a close relative of rheumatoid arthritis it certainly doesn't seem to respond to the same drugs - although, the DMARDs are used to prevent the damage to the joints which happens in RA and doesn't in PMR. As I have learned a bit more about RA I have found that the muscular problems and stiffness (which parallel the main component of our disability in PMR) often remain even with the newer and very effective RA treatments and there are some rheumatologists who are diagnosing fibromyalgia as well as RA - although in some cases the symptoms complained of by the patients sound more like PMR. It is a complex problem there is no doubt about that and I do wonder if there are different versions of PMR - after all, the name merely describes the symptoms \"many painful muscles in flux (in different places at different times)\" - so some people need treatment for different periods of time.

If it were me I think I would want to try with reducing the steroids very very gradually this time - and keep the azathioprine as a reserve at a much later stage. Just because you can't get below 10mg a day or so in the first couple of years doesn't mean there's something wrong. For the first time yesterday I found repeated comments that whilst many patients do get off steroids in a couple of years, a high percentage (more than 40% comes to mind) need treatment for 2 to 4 years and some need a low level

6

This is from PatC - otherwise known as PatsyAnn!! Sorry everyone - got a bit confused about how to use the system.

Jill - I started an earlier thread entitled \"Methotextrate\" where I outlined my experience so far. My original doseage was 60mg back in April, after I had been very poorly for 5 weeks. I am convinced that my current GP is not well informed about GCA or PMA - hence her recommended reduction from 20mg to 15mg in one step 6 weeks ago. I have been on 20mg since then, awaiting the results of the visit to the Rheum Consultant and his advice about Methotextrate. It was in response to this query that he has recommended Azathioprine. Perhaps its cheaper!!! The Azathioprine would also require a fairly arduous regime of blood tests every fortnight, to check liver funtion, renal function and a full blood count.

Just to confuse things even more, I have just moved house so will have to change to another surgery. This gives me a chance to start a relationship - hopefully with a better informed GP.

Eileen - thank you so much for all your research. From what you say, I do think it would be best if I try the gentle reduction of steroids first - after all I haven't done this yet.

I had a SED blood test this morning and plan to see my GP on Friday to discuss the results and the contents of letter from the Consultant. Thanks to you all, I will be much better informed! I will ask for the steroids in smaller denominations so that I can start the reduction program. I will also tell her about my plans to move to another surgery and get that moving.

I can't tell you how great is to know you are there!!

7

Hi Pat+!! :lol:

Just remembered a statement in one of the textbooks - any reduction should never be more than 10% of the current dose. So that means 20 down to 18 is OK, no more. 20 to 15 is 25%, a massive drop, no wonder you didn't feel too good! For simplicity (using 5 and 2.5 mg enteric coated pills) I would have tried dropping from 20 to 17.5mg on one day the first week, 2 days spaced over the second week, 3 days spaced over the 3 week and so on as long as I managed OK. Even more gentle would be to use 1mg tabs and do the same 1 mg at a time.

In fairness to your GP, had you had only PMR and STARTED at 20 mg for a few weeks, a drop to 15 would probably been fine but you had already been on much higher doses for a few months. I'm sure you've already read loads on here about reducing and will have seen that some people need very small drops and to do them very slowly. If you haven't already done so, have a look at the pmr-gcauk site (google that plus northeast support site to get there) you will find articles about patient experiences with steroids, PMR, GCA and reducing. Ragnar, a Swede, developed a very gentle reduction scheme for himself and was eventually successful. And since you have had GCA, it does seem it will be more difficult to get right down without risking a flare. MrsK and MrsO are your experts here - both have had GCA - and I'm sure will be along soon with their advice from personal experience which is of tremendous value.

But the heavy guns? I repeat - keep them for when the simple regimen doesn't work.

EileenH

8

Hello PatC

Like you I also have PMR and GCA but fortunately for me I was able to reduce (under the direction of a very clued up rheumatologist) from the initital starting dose of 40mgs to 30mgs in 2 weeks and thereafter successfully managed weekly drops to 20 and then 15mgs. It wasn't until I reached 5mgs that the fun began again!! I then had to increase back up to 10mgs on a couple of occasions due to flares and was advised to stay on 5mgs finally for some 5-6 months before reducing again. At that stage I really thought that I would be one of those people who remained on 5mgs for life as Eileen has mentioned. I stuck to an anti-inflammatory diet with very little carbs and sugar and am sure that has gone a long way to helping me finally get to where I am now at 1mg although I still have my fingers crossed! As Mrsk has often said, PMR will go when it wants to and not before but having said that, I believe we still have to do everything we can to help it on its way!

Unlike a few posters on this site, my pain levels and inflammatory markers have always corresponded, ie increased pain = increased inflammatory markers so the rheumatologist relied on regular blood tests showing normal readings before each reduction.

Although I have given you the example of my experience above in the hope that it may help, I would add that we are all very different both in our pain levels and response to steroids. In your case, if 20mgs has been controlling the pain for a couple of weeks and your blood tests are normal, then if it was me I would now try 17.5 or 18 as a next drop. Hopefully, this time you will be successful and I have my fingers crossed for you.

MrsO

9

Hallo Pat and very sorry to read of your horrors. Fingers crossed for a better-informed GP when you move. I'm sure someone will warn you of the stressinvolved in moving house and not to be surprised if you have to boost your Pred. a bit. Just considering moving was probably the trigger of my second bout of PMR after 5 years completely clear but perhaps I'm made of weaker stuff!

Re Eileen's interesting bit about no reduction being more than 10% reminded me of the experience of a friend many years ago. He had\"just\" GCA and it took a while for him to be diagnosed. Too young; wrong gender. He started on 60 and finally finished eleven years later, completely cured, no recurrence. BUT he frequently regressed until his wife remarked that as the dose reduced they were a larger %. You wouldn't need a maths degree for that insight you might think. She bought a pill chopper and drastically modified the reduction steps and they finally got there. Luckily he was ok with the bog standard pills and didn't need the coated ones that, obviously you cannot chop.

Good luck with fiding a regime that works for you and may the sun shine on your moving day. BettyE

10

PS WHoops! :roll:

You have already moved house! Must read more carefully.

My excuse.I spent the afternoon trying to persuade my Int. Connection that I was me. Finally a splendid young man from virgin talked some sense into it. Interestingly having felt a bit \"off\" all AM the stress of fighting a stupid computer made me feel much better. How silly is that? But I have often reported on here that I seem to have too much adrenalin so maybe a fight was what I needed. Hope your move went well Pat. BettyE

11

Patsann, Pat C and Patsy Ann (Yippee I just love it - so many names - royalty comes to mind).

Yes, its me, coming along to add my sixpennorth.

It will be four years Feb next for GCA. Taken this long to finally get down to 3mg and holding - just been down for 1 month and won't go down to two for another two months. I follow the this regime. ie When down to 10mg drop 1 mg every month, when reach 5, drop 1 mg every three months. Why did it take so long - two flare ups and back to 60mg first time, 40 mg second time.

Been offered Methotextrate etc - refused them all after careful investigation and as they did not cure it, I stuck to the drug that had been on the market longest ie pred.

Pred with all side effects, grim and horrible as they are, you don't get them all.

Decided when looking at the side effects of the others offered and how young they were, I would just say, thanks but no thanks. But it is a very personal decision, but you know yourself best and you can decide which road is best for you.

Unlike Mrs O, my CRP rate can go up and down and guess who panics, the GP, not me. ESR is a marker/guideline and can shoot off the scale, if I get some other infection or problem and the CRP does the same.

I know what the GCA symptoms are and at the first sign of trouble, I up the dose and contact with GP asap. If I cannot see him I will up it until its gone. My GP insists I keep 60mg of steroids all the time as an emergency supply. I am glad he insists, I am happy knowing they are handy.

Steroids stand between my sight and the loss or partial loss of same. And I will not risk that for anybody.

Finally, the bottom line is that everything you are offered apart from Pred (whihc is a steroid) is a steroid sparing agent. Not a cure - a 'steroid sparing agent'. These drugs have been developed for other illnesses, not specifically for PMR and/or GCA.

I really want a cure - or a friendlier medication.

Mrs O is better at PMR and GCA as I only have GCA.

Like Mrs O, I eat natural as far as possible and take Manuka Honey, Tumeric, Glucosamine (Osteo P). Oh and a large brandy now and again (purely medicinal of course!!!)

PS Download the BSR Guidelines on both GCA and PMR, put them in your handbag in case the new GP is not up to speed. GCA - you are 1 in 50,000 last time I looked. Pretty exclusive club so the stats say, me I don't believe the stats, but do know that I am the only the second patient in my GPs practice and that was only because one of the GPs had a case over 25 years ago.

Good luck and may both of them take a long walk off a short pier and soon.

12

I am with Mrs.K where the steroid sparing drugs are concerned.

While I was trying ( unsuccessfully ) to live with PMR without steroids I developed a pain slightly above my left ear and rushed off to the surgery in case it might be a symptom of GCA. I was feeling fraught, anyway, partly because of the pain of PMR without steroids and partly because the said steroids had caused me a lot of problems and I wanted to avoid them if possible but not at the risk of my sight. First doctor asked would I allow her to seek a second opinion ( yes, please, by all means ) Senior partner came up and said no need for biopsy, no sign of claudication and a very strong pulse at the site of the pain and no need for \" even scarier \" drugs. I didn't ask what they were. BettyE

13

Hi there everyone

I have now seen my GP to discuss the Consultants opinion etc.

1) On the question of moving to another GP, she wants to keep me on her books until eveything is sorted out. I'll see how things go with this.

2) I asked why Azathioprine has been recommended and her reply was that as my SED rate had gone up again (from 45 to now 76) they feel that the withdrawl process is going to be lengthy so I need a steroid sparing drug in anticipation. Especially because of the weight gain, bruising, cramps etc. I can only take it if my body has a certain enzime, and the blood tests take a while so nothing will happen immediately. She did acknowledge that how I feel is as important as the figures, and as I am currently feeling ok, she has agreed to a 1mg reduction to 19mg for the next fortnight when I will have more blood tests.

I'm hoping that the SED figure will come down in the fortnight, and I will then be able to argue against having Azathioprine. Fingers crossed.

3)

14

Hi Patsyann,

The ESR (sed rate) is merely a guide and it is accepted by the experts that the ONLY guide to how your taper is proceeding is how you feel. Just because your ESR goes up does not necessarily mean that your steroid dose needs to go up. It applies just as much as the converse - I have never had a raised ESR and at my worst was in constant pain and almost unable to get out of bed and stairs were done on hands and knees! So I didn't have PMR they said as I was too young anyway. The ESR can be affected by other things and is utterly non-specific, it's not diagnostic of anything whatever anyone tries to tell you - it indicates there is something going on but not what. There are some of the contributors to this forum who do have increases in pain that are paralleled by higher ESR values but not all of us do.

I just looked back over your post - after GCA in the spring to be down to 20 and trying 19 seems not a bad rate of progression to me and it is accepted that getting the dose down after GCA is much more difficult. But I am not a doctor. However - I do know that monitoring the clinical picture is more important than looking at lab values.

Good luck and keep us informed,

EileenH

15

Hello again Patsyann

You have mentioned your Sed Rate (ESR) increasing as being the reason your GP is recommending Azathioprine. Although as I have previously mentioned I am one of many people whose blood test levels always increased alongside increased pain, I do agree with Eileen that raised ESR can be a sign of things other than PMR going on in the body. However, do you also have CRP (C-Reactive Protein) blood tests as this test is generally considered to be a better marker of inflammation in the body. At diagnosis in my case both these tests showed very high inflammation but especially the CRP one and therefore both tests were always carried out prior to any dose reduction and I have been led to believe that the CRP test is the more important of the two.

The good news is that you are feeling ok at the moment and reducing by just 1mg to 19, so slowly does it, take things easy and better luck this time.

MrsO

16

Hi all (again)!

I just posted part of this over at the other thread about bruising but I thought I'd repeat it here for ease of relating to this thread.

During this afternoon's online reading session :lol: I noted the following piece of information in a chapter in a medical textbook dealing with the treatment of GCA and the use of the so-called \"steroid sparing\" drugs:

30% of patients who got off steroids in less than 2 years had relapses of GCA and/or PMR. An even higher relapse rate was noted for patients who were on steroids for less than a year.

There have been some trials of the idea of using very high doses of intravenous steroids at the start of treatment of GCA for a short period until the inflammation has been totally controlled (on the basis of the ESR values) and then changing over to longer term lower oral doses. This has seemed to offer a promising way of dealing with a nasty disease which threatens your sight as it was associated with good recovery rates and few relapses.

These points do suggest to me that it is very important that the inflammation in the blood vessels MUST be got under control at the outset for a successful longer-term result - and that it is a mistake to be too hasty in trying to get off the steroids.

In addition, I now have several pages of notes from several medical journal sources about the use of the steroid sparing drugs. To summarise:

There have been a few attempts to use steroids along with other immunosuppressive drugs to try to reduce the amount of steroid given to patients and so reduce the longterm adverse effects of taking steroids. The results of these carefully controlled studies (as opposed to anecdotal reports) have been mixed and provide contradictory opinions. In the case of methotrexate, two studies showed a slight reduction in the amount of steroid the patients took but no difference in the adverse effects over a long period of time whilst another showed no benefit at all. No benefit is seen until after the MTX has been taken for a year and it needed to be started at the initiation of therapy.

In the case of azathioprine, it also takes a year for any advantage to be identifiable and the overall benefit is not as good as MTX . It was said that azathioprine could be considered for use in \"patients with refractory disease who have other risk factors which make the use of steroids undesirable and who are contra-indicated for MTX\".

Both MTX and azathioprine are associated with adverse effects. Another drug (an anti-TNF substance) was dropped after 22 weeks as being of no benefit at all and possibly detrimental, despite the fact that this \"TNF factor\" referred to has been identified in the blood vessels in patients with GCA so apparently may be involved in the disease process.

In a nutshell: if you are old, frail and have steroid-induced or steroid-contradictory problems such as diabetes, osteoporosis (to the extent of having fractures) and the PMR/GCA isn't responding well to the normal dosage of prednisolone (15mg/day) then MTX and azathioprine could be considered. But steroids are the gold-standard for both GCA and PMR and should be used in the first instance with the other stuff being held back for when it is unavoidable.

It was also said in one publication that in the case of GCA, in particular, dose reduction once at 20mg per day should be at no faster than 1mg per month, possibly less, with the reduction rate being slowed in the event of any sign of relapse. PMR patients may generally get off steroids in 2-4 years but it is not unknown for treatment to be required for 5-7 years. I've already mentioned elsewhere that reductions should never be more than 10% of the current dose in any case.

And just so you know: this information stems from papers and textbooks by groups of rheumatologists, ophthalmologists and neurologists who are actively researching and working in this field. The most recent

17

Hi Eileen and wow :wow: - what fantastic research with very interesting stats.

Seems like I was one of the lucky ones then to manage to reduce below 20 by 1mg a month with my bloods remaining normal right down to 5........when the fun began!

No wonder even the experts get confused when some GCA sufferers have the TNF factor in their blood vessels and yet the anti-TNF drug proves to be of no benefit!

Thank you Eileen for all your hard work on our behalf - I found this very interesting reading and after all that you're the one who now definitely deserves a bubbly :bubbly:

Off to watch \"Strictly\" now - poor Anne Widdecombe, but I'm sure we'll see her next week!

MrsO

18

Thanks again, Eileen for all your work on our behalf.

but it is not unknown for treatment to be required for 5-7 years

As I have previously reported, my friend ( male and in his early fifties at the time ), took 11 years to get off but was and remains fine, having sustained a multiple heart by-pass and will soon, as he loves to tell us, be in his ninth decade. I quote him to myself when I want to hurry to get to the end of steroids.

Wonderful two days here and another to come, we are told. Hope you all had the same. Best wishes for a good week. BettyE

19

Sorry. Forgot AGAIN to press Quote at the end. Hope all is clear. BettyE

20

Tee-hee - maybe the site has PMR/steroid brain fog too!!!!!!!