Leflunomide

Started by Smachak, May 17, 2017, 01:38:28 PM

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Smachak

Hello, my dog is trying to get over autoimmune meningitis since last August. Has had several relapses while on prednisone. Tried to add cyclosporine but he got very sick on that.  About the only option left is leflunomide.  Anyone have any experience with this drug? Side effects, how well does it work?  Thank you.

Catherine

Did you try Azathioprine as well? I have no experience of Leflunomide but my AIHA dog did very well on Azathioprine and
Preds.

There have been a few posts about Leflunomide, just put the name in the "search" function on the site.

Smachak

The vet thinks that the leflunomide would have less side effects and be less harsh than the azathioprine.  Maybe because his liver enzymes are already  somewhat elevated from the pred.  Thanks for the tip about searching!

Catherine

Some vets do see Azathioprine as a "baddie", maybe because of elevated liver enzymes. It may not be right for every dog but I found it okay with my dog although she was on the lesser 25mg a day tablet so approximately 1mg per kg daily.

Jo CIMDA

Hi

Leflunomide is being used more these days and I have known dogs to reach remission whilst being treated with leflunomide.   Relapses of SRMA are not uncommon in the first few years of treatment but it usually settles down and long term remission is achieved. 

It is a shame that the preds did not achieve remission.  Steroids are usually very effective with SRMA (steroid responsive meningitis).  Was your dog on a good protocol?  Check it against the one below.  This is an excellent protocol and can confidently be used as a guide.

Jo


Example: Reduction Protocol for prednisolone:
Clinical Immunology of the Dog & Cat , 2nd Edition,  by Michael J Day
Professor Michael DayBSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS 

Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.
This example is based on a dog receiving an induction dose of 1.0mg/kg/q 12hrs (q = every)
Dose                           Duration (based on clinical effect)
1.0mg/kg/q 12h                          10-28 days
0.75mg/kg/q 12h                       10-28 days
0.5mg/kg/q 12h                         10-28 days
0.25mg/kg/q 12h                        10-28 days
0.25mg/kg/q 24h                        10-28 days
0.25-0.5mg/kg EOD                    at least 21 days
0.25-0.5 mg/kg every third day      at least 21 days
Every reduction is made after consideration to improvement of clinical signs, blood results and side effects of the drugs.

Smachak

I don't know exact pred dose while he was in intensive care for 4 days, after he got out he was on 20mg but could only keep him on that for 2 weeks as he he went from 40 lbs to 30 lbs in less than 7 days.  Since then his taper has been very slow less than the 25%, and also when starting taper it is done eod, then every two days.  Every time he hits 10mg day he starts to have problems....and never sure if it actually relapse as symptoms always seem to be different, but always involve pain somewhere on/in the body in different areas.

Jo CIMDA

Hi

Anecdotal evidence suggests that using the Michael J Day protocol as a guide, and gradually reducing the DAILY dose of preds until it get to a very low dose, and then to go over to every other day dosing, reaps better results and more chance of long term remission.

When steroids are used in high doses the aim is to bring the disease under control and into remission with the initial treatment regimen, but this requires an excellent drug protocol.  Relapses are always possible but by leaving the dog on a reducing daily pred dose for longer, and then go to every other day and every third day dosing etc...... often achieves remission the first time around and avoids recurring relapses and having to return to a greater use of steroids or another immunosuppressive drug regimen.

SRMA has a good prognosis and long term remission, especially as the dog is out of adolescence and into mature adulthood, is very realistic.

If the present side effects of the preds are not too severe then he might be able to cope with raising the preds to 20mg (the dose he came out of hospital on) and then reduce the dose with the guidance of the Prof Day protocol.  You may avoid having to use Leflunomide or any other drug.  Or you could add leflunomide or Azathioprine and also raise the preds to bring the disease under control, and then reduce the preds whilst still having the added support of another immunosuppressive drug.

I believe the problem you are seeing is as a result of going from a relatively high/middling dose of preds to every other day dosing, without gradually  reducing the preds to a low daily dose first.   I have never known this regimen to work and relapses are predictable.

Jo


Smachak

Jo,
I guess I was not very clear, but this was the method used...went from 20 to 15mg for a month, then went to 10 for a month..next relapse went from 20 to 15 for a month, then 12.5 for a month, then 10....every time there was a reduction went for 2 to 3 weeks in with eod, then every second day then 3 days then to finally new dose every day.  Slower taper than on the listed method.  Dosing was also split to every 12 hrs.  The problem now is the side effects of the pred are taking a toll after 9 months. Also never sure if it is really a relapse because meningitis has similar symptoms as the pred, and here in US CRP testing cost $270, so it is not done when reducing pred.  Also my dog has IBD so CRP can show up high even without meningitis relapse.  Very frustrating.  I also think there may be other issue autoimmune going on as he has always (he is 6) had hypersensitive to touch at times...another autoimmune??? or all slight bouts with meningitis.
Thanks for your help.

Jo CIMDA

Hi

It can be very confusing when there is more than one problem and also, the numerous side effects that can be seen with long term use of preds throws a spanner in the works too. It is sometimes hard to know if it is the drugs or the disease/s that is causing the symptoms.  Also, when a dog has had one AI disease they are predisposed to get others.  That doesn't mean they will, but it is possible.

I am sorry I misunderstood your first post about the dosing.  Clearly the preds have been reduced gradually, but there are no guarantees with AI disease and sometimes a dog has to stay on a low maintenance dose of steroids to achieve long term remission.

Having said that, sometimes these relapses occur for a few years following the initial onset, and then, for no apparent reason, it all settles down and it may never happen again, but there is no way of knowing. 

Introducing another immunosuppressive drug is a good idea and hopefully this will achieve remission.  It is very frustrating though.

Jo




Smachak

Thank you Jo!  I have just been reading on cell oxidative stress and glutathione...seems like there is some information and studies out there that point toward glutathione as being a very effective antioxidant as well as antiinflammatory in autoimmune diseases.  Have you or anyone you know have experience with this?

Jo CIMDA

Hi

I don't have personal experience but I have read about it and have listened to some of the very interesting webinars by Dr Tom O'Bryan.

It is very important to limit potential trigger factors because once an AI disease is in remission, for it to become active again, or to get another AI disease, it has to be triggered.

I do think antioxidants are important, and if possible a natural and organic diet to minimise trigger factors and pollutants that may re-trigger AI disease.

I think a diet high in glutathione can only be a good thing but I understand taking supplements may not reap the same benefits.

I am very interested in any new information you discover and how you plan to use it because sharing on a forum like this results in good practise.

Jo