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Author Topic: Initial IMPA treatment - does this sound right?  (Read 120 times)

MelAndZen

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Initial IMPA treatment - does this sound right?
« on: May 22, 2018, 10:13:51 PM »

So I am a brand newbie with IMPA.. we were diagnosed on April 15th when suddenly we woke up and she couldn't put any weight on her back end, and was throwing up. I thought she was bloating so I took her to Emergency. We had ultrasounds, xrays, blood tests, ANA test, tick borne disease  test and joint taps. So far, everything was clean so IMPA is primary diagnosis.

Once diagnosed- the internist immediately put her on a combo of Prednisone and Azathioprine and various supplements. (Cosequin and omega 3) At time, my dog weighed 96 pounds and the original prescription was:

Prednisone 20 mg- 1 orally in AM and 1 orally in PM
Azathioprine 50 mg- 2 orally once daily for 10 days - then 2 tablets every other day

 After 3 weeks I ended up switching vets and got a second opinion. (Long story) And after another joint tap, we decided we could start decreasing the Predisone which is good because she is not tolerating it well. In the month we've been doing treatment she is suffering muscle wasting and went from 96 pounds to 89. Her current prescription is:

Prednisone 20 mg- 1 orally in AM and .5 orally in PM
Azathioprine 50 mg- 2 tablets every other day
Denamarin - 2 orally once a day

I'm trying to keep her exercising doing low-impact exercises daily and water treadmill once a week. Besides the supplements I mentioned above, I made a chicken/veggie broth that is packed with vitamins and minerals including fenugreek and turmeric to add to her food. But overall she has no energy and is losing weight and muscle tone. Really just wants to sleep all the time and I haven't seen her want to run in weeks. She always was a mellow dog but she'd have periods of friskiness and playfulness every day that I don't see right now and I'm scared that I'm never getting my dog back.  Everything I've read says that dogs can live a long, normal life so long as it stays in remission. Is that true?

If she continues to be in remission, and we are able to get off the prednisone.. will she want to start playing again? The vets are very matter-of-fact and all they talk about is what we are doing in the NOW.. nothing about what to expect for the future. (Which makes sense I guess, given all the unknowns.)
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Jo CIMDA

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Re: Initial IMPA treatment - does this sound right?
« Reply #1 on: May 23, 2018, 07:39:03 PM »

Hi

The treatment that Zen has received is not the usual recommended immunosuppressive drug regimen necessary to bring IMPA under control and into remission.

A dog weighing just under 44 kg (Zen's original weight) should be on 1mg/kg/12hours, so an appropriate  dose of prednisolone is between 40-45mg/kg/every 12 hours.   44mg pred twice a day is considered immunosuppressive.  Unfortunately Zen has not received an immunosuppressive dose of preds.

In addition, if Azathioprine is used as a 'combination' immunosuppressive therapy drug then:

Taken from Plumb's Veterinary Drug Handbook, 8th Edition:

Azathioprine:   'general recommendations are:  Initially, 2mg/kg once daily for 1-4 weeks.  Then the dosage is reduced to 0.5-2mg/kg every other day.  After treatment has begun a lag period of at least a week and often as long as 3-5 weeks is required before there is significant clinical immunosuppressive efficacy.'


Azathioprine has been used for decades as a combination drug alongside prednisolone for the treatment of inflammatory AI diseases in dogs, and it has been very successful, but it had always been considered that it takes at least 10 days to kick in and it could take up to 6 weeks before a good level of immunosuppression is achieved, so the dose of Azathioprine that Zen has received has not been sufficient to achieve adequate immunosuppression.  The quote above from Plumb's Veterinary Drug Handbook (which is considered to be one of the best veterinary drug books and used worldwide) is the latest edition and therefore the information is up to date.

The idea is to significantly suppress the immune system and virtually wipe it out, and by doing this the production of destructive immune cells is stopped.  Once the immune aggressor is removed the body will naturally start to repair and produce synovial fluid to lubricate the joints.  After being on an immunosuppressive dose of prednisolone for a period of 10-28 days (usually, the initial dose is for at least 21 days depending on the side effects of the preds) the dose is reduced by about 25% and reduced again after 10-28 days etc.... (see the Michael J Day protocol below).  By this time the Azathioprine is starting to take effect and this allows the preds to be reduced sooner if necessary.  It is hoped that this will be an adequate amount of time to calm the immune system and for it to return to normal function.  The drugs are then weaned off over a period of approximately 4-6 months.

From the clinical signs you are still seeing it appears that Zen is not in remission and given the drug regimen she has been on it is no surprise.   It is likely that if you reduce the meds again her clinical signs may worsen.  This is because the inflammation has only been tempered and not fully suppressed.  The correct dose of drug and duration is crucial to a good outcome and achieving long term remission.  A dog that has had IMPA and has reached true remission will behave as a normal dog and enjoy life to the full again without pain. Until you see this you can assume that Zen is not in remission - but it is very achievable!

If Zen is coping well with the side effects of the preds then it might be possible for your vet to increase the preds back to an immunosuppressive dose and also increase the azathioprine, which should be having some small effect by now.  Zen is a large dog and they don't cope so well with the side effects of preds but all dogs cope differently and this has to be assessed by a physical examination and also checking on how the liver is coping.  Also, as Zen has had some weeks of being on prednisolone - even though it is not in immunosuppressive doses - and there will be an accumulative effect and this has to be considered when deciding on a new immunosuppressive drug regimen.

Zen should also be on a gastroprotectant such as omeprazole or Ranitidine to protect her stomach from the excess acid that the preds produce.

See the information below.  This is the best immunosuppressive drug protocol I have come across and it can be confidently used as a guide - but take into consideration the fact that Zen has already been on steroids for a few weeks.  You need to have a chat with our vet about how to go forward and focus on  the goal of long term remission.

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.

Prednisolone:  "Doses above 2.2mg/kg/day do not give more immunosuppression but do cause more side effects. Many internists believe that prednisolone doses should not exceed 80mg per day, regardless of the dog's weight."  Plumb's Veterinary Drug Handbook Eight Edition.

The dose of azathioprine 2mg/kg/24 or 48 hrs, can be reduced initially by giving a lower dose tablet per day, or gradually reducing from daily dosing to every 2nd day, every 3rd day, every 4th day etc.....  Remember, azathioprine tablets should not be broken or handled without gloves.

How Do I Know if My Dog Will Relapse?
Until you have attempted to wean your dog off of the tablets for the first time you will not know if he is likely to relapse or not.  Sometimes during the weaning off process, before you even get down to an every other day dose, he may relapse.  If this happens then the drug dosage has to be raised, probably up to the last dose before the relapse (maybe a little higher, depending on the severity of the relapse) and then start the weaning process again.  If this happens again, then you and your vet may have to settle for keeping him on a low maintenance dose to achieve a good quality of life. A low, every other day maintenance dose of prednisolone is preferred to enable the dog’s liver to rest in between doses. There are many autoimmune diseases that carry a good, drug free prognosis.  The more common, serious autoimmune diseases that may not need long term steroid therapy are: primary immune-mediated polyarthritis, autoimmune haemolytic anaemia and thrombocytopenia. However, as previously stated, all dogs are different and it very much depends on the individual dog, the severity of the disease, the experience of the vet and the vigilance and compliance of its owner.
If a relapse occurs whilst the dog is still being treated then true remission has not been achieved.  If the dog has achieved remission and has enjoyed a period without drugs or is on EOD maintenance drugs, when a relapse occurs or he develops another autoimmune disease, he has encountered a ‘trigger factor’ which has induced this change.







 
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MelAndZen

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Re: Initial IMPA treatment - does this sound right?
« Reply #2 on: May 23, 2018, 09:32:09 PM »

From the clinical signs you are still seeing it appears that Zen is not in remission and given the drug regimen she has been on it is no surprise.   It is likely that if you reduce the meds again her clinical signs may worsen.  This is because the inflammation has only been tempered and not fully suppressed.

Hi Jo

Thank you for taking the time to respond to my post. Well, I have to say this is really disturbing to me. I have already switched specialists twice and this one came under very high recommendation, mostly because of her experience with IMPA. I don't know why she would have continued on the regime that the other vet prescribed except when they did the follow-up and 2nd joint tap, Zen showed no inflammation what so ever. Would that still be classified as "tempered?"

Also, (And forgive me if this is an uneducated question.) Considering I'm seeing vets who are located in America I wonder if they are using Merrick's Veterinary manual instead of Plumb's? Would there be a difference in dosages?




If Zen is coping well with the side effects of the preds then it might be possible for your vet to increase the preds back to an immunosuppressive dose and also increase the azathioprine, which should be having some small effect by now.  Zen is a large dog and they don't cope so well with the side effects of preds but all dogs cope differently and this has to be assessed by a physical examination and also checking on how the liver is coping.  Also, as Zen has had some weeks of being on prednisolone - even though it is not in immunosuppressive doses - and there will be an accumulative effect and this has to be considered when deciding on a new immunosuppressive drug regimen.


Zen is already showing signs of no tolerance to Predisone, and that is on half the dosage that Plumb's Handbook recommends. What's more, after 3 weeks on the current regime her liver levels were up and that is why they prescribed the Denamarin. The only drug that was prescribed for her stomach was by the first specialist in the very beginning and mostly for her initial vomitting. She has prescribed Pepcid which active ingredient is Famotidine. Is this also a gastro-protectant?
« Last Edit: May 23, 2018, 10:07:44 PM by MelAndZen »
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Jo CIMDA

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Re: Initial IMPA treatment - does this sound right?
« Reply #3 on: May 24, 2018, 05:43:36 PM »

Hi

If Zen had been on steroids prior to the 2nd joint tap then this will mask the results. Prednisolone suppresses the immune response and this is why a dog should be steroid free for approximately 14 days prior to a procedure for the results to be reliable.

'I wonder if they are using Merrick's Veterinary manual instead of Plumb's? Would there be a difference in dosages?'  

The answer to this question is no, an immunosuppressive dose of prednisolone for a dog is 1mg/kg/12hours.  It used to be 1.1-2.2mg/kg/12hours but recent studies have suggested that a dose of 1mg/kg/12hours adequately suppresses the immune system and any higher dose than that will only cause greater side effects without greater immunosuppression. A lesser dose is considered to be an anti-inflammatory dose and not immunosuppressive.

If Zen's IMPA is not in remission, and the side effects of prednisolone are becoming a problem, then perhaps another drug can be considered such as leflunomide or mycophenolate.  These are two relatively new immunosuppressive drugs to veterinary medicine but they seem to be having some good effect. 

Famotidine is a gastroprotectant and it should still be included in Zen's drug regimen.

Jo

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MelAndZen

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Re: Initial IMPA treatment - does this sound right?
« Reply #4 on: May 24, 2018, 07:24:42 PM »

Thank you for the info!

I have a follow-up appointment on Tuesday and I will bring all of this up with the internist.

-m
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Jo CIMDA

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Re: Initial IMPA treatment - does this sound right?
« Reply #5 on: May 25, 2018, 10:38:54 AM »

Good luck on Tuesday.  Thank you for the picture. Zen is such a beautiful  girl.

Jo
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