Introduction

[Catherine]

Has she stopped the 30 mg of Leflunomide once a day then? I have no experience of Leflunomide but if it does a similar job to Azathioprine I would have reduced the Preds and then stopped the Preds completely before reducing and stopping the other drug.

If she is only having the Preds now I agree with you that it would be better to keep to the same amount daily if Sophie is coping well with the medication. So 7.5mg daily and then eventually to 5mg daily rather than every other day or different amounts each day.

[dalebrook.bp@gmail.com]

Sorry Jo - yes she is still on the Leflunomide - 30 mg per day.  I assume you would still keep doses even of two days - ie 7.5mg per day?

Patricia

[Jo CIMDA]

Hello Patricia

It is good news that Sophie is doing well. 

   I agree with Catherine, and I would use the reducing protocol by Michael J Day as a guide - but you can go slower at this stage if the side effects of the preds allow.  Anecdotally, if the last stages of immunosuppressive protocol is taken slowly, on a daily basis,  it usually reaps better results and a greater chance of reaching long term remission.  As long as she is coping with the side effects then there is no rush, but no two dogs are the same and the protocol has to be tailored to the individual. 

I am not a vet so I can only give a personal opinion on what I would like to do if Sophie were mine. In an ideal situation 10mg a day can be reduced to 7.5mg a day and if all is well it is best to eek out the duration to 14 days and if clinical signs allow I would stretch that to 16 or 18 days and then reduce to 5mg per day.  Then, one option would be to reduce from 5mg every day to 2.5mg every day -  or you could go 5mg and 2.5mg on alternate days. Again I would eek out the duration of this small dose for up to 21 days. Then you can go 2.5mg every other day etc., etc..... and eventually wean off altogether.   

There is no hard and fast rule at this stage of treatment but what you want to achieve is stability and homoeostasis and when dogs are on steroids for many months, taking the last stages slower seems to give a better chance of achieving this. These low doses are having no real therapeutic effect but anecdotally the evidence shows by giving a very low every other day dose, that is very gradually weaned down,  is less of a shock to the body and as the dose is lowered the body's own cortisol will naturally start to produce the correct level of cortisol needed to function normally.

Perhaps you can discuss this option with your vet.

Jo 

[dalebrook.bp@gmail.com]

Thanks for your help, Jo.  I feel much happier about the 7.5 mg a day, so I'll discuss it with the vet - Sophie goes for more bloods tomorrow and haematology and biochemistry are both going to be done.  She just had haematology a couple of weeks ago as her PCV had gone down the time before and he wanted to check that it had gone up to her usual level which seems to be around 38.  Apart from the ravenous appetite, which I guess might have become partly a learned behaviour, her other pred side effects are not too bad, so in view of her relapse, we have been taking things pretty slowly.

Thanks again - I really appreciate being able to discuss things with you and getting your advice.

Kind regards

Patricia

[dalebrook.bp@gmail.com]

Hi Jo

Have just been to the vet and discussed Sophie's dose reduction if the bloods taken today are looking OK.  He is very clear that he thinks it should be 10 mg one day and 5 mg the next day, to help stimulate Sophie's own system.  Having looked at Michael Day's protocol, this seems to fit, as I see that the protocol has doses on every other day after the initial period of time - it is now 6 months since Sophie relapsed, so the timeline seems about right.  She is basically going to have 7.5 mg per day over the two days.  I guess I am very nervous after she relapsed when on an every other day dose, although it was 5 mg every other day, and no dose on the in between day, so much lower doses.  And she will still be on the Leflunomide, which she wasn't having when she relapsed.  What would your feeling be about going with the 10mg one day and 5mg the next? 

Her bloods are looking ok I think - Alk Phos is down from 181 to 89, ALT from 319 to 149, AST from 62 to 59, CPK has gone up from 401 to 527.  Pathologist comment:  "Ian, the liver parameters are looking improved - at these values may be due to the drugs used - induction/increased permeability.  The lipaemia may be due to the steroids?"

The haematology is: RBC 5.22 down from 5.35, Lymphocytes Abs up from .2 to .4, Monocytes Abs down from .5 to .1, PCV is .37 down from .38MCH down from 26 to 25, MCHC down from 363 to 354, WBC down from 17.1 to 12.7, Neutrophils Abs down from 15.9 to 11.4, Lymphocytes Abs up from .2 to .4.  All other results are within normal ranges.  Comment: "Ian, the RBC parameters are low normal, marginally trending down again.  The haemoglobin (even though performed manually) is probably still artefactually increased due to the lipaemia of the sample.  This HCT is a manual PCV.  The MCV is still high normal so no indication of any iron deficiency at this stage (although at end June the MCV did drop to low normal)."

Thanks again for your help.

Patricia

[Jo CIMDA]

Hi Patricia

Personally, to give the best chance of reaching long term remission,  I would still prefer to go 10mg one day and 7.5mg the next but much depends on whether Sophie is coping with the side effects of the drugs and if the long term use of preds are causing the drop in PCV.  Of course the Leflunomide may be reducing the level of PCV too. 

  I can only give a personal opinion. Ultimately you have to agree the dosage with your vet.   I don't think you have any choice but to go with your vet and hope that as the dose of preds is reduced the PCV will rise and you can then start to reduce the leflunomide.

Fingers crossed once you have weaned down the preds the blood values will return to normal.

Jo

[dalebrook.bp@gmail.com]

Hello Jo

We went with the 10 mg one day and 5 mg the next day, and Sophie seems to be doing well. 

These are her latest bloods (I have had her cross matched with a potential donor in case of relapse, so these results are included too.  Obtaining blood quickly would be very difficult in New Zealand as we don't live in Auckland.)

* Cross match See Below
RBC 5.34 L x10^12/L 5.5 - 8.5
Haemoglobin 130 g/L 120 - 180
HCT/PCV 0.37 L/L 0.37 - 0.55
MCV 70 fl 62 - 74
MCH 24 pg 20 - 25
MCHC 349 g/L 320 - 360
NRBC 1 /100LEU 0 - 2
WBC 11.6 x10^9/L 6 - 17
Neutrophils % 91 %
Neutrophils Abs 10.5 x10^9/L 3 - 11.5
Lymphocytes % 2 %
Lymphocytes Abs 0.2 L x10^9/L 1 - 4.8
Monocytes % 5 %
Monocytes Abs 0.6 x10^9/L 0.2 - 1.4
Eosinophils % 2 %
Eosinophils Abs 0.2 x10^9/L 0.1 - 1.3
RECIPIENT: Sophie
DONOR: Bella
RESULTS:
Minor Crossmatch :
There was agglutination seen microscopically for the above animals in minor crossmatch.
Major Crossmatch:
There was no agglutination or haemolysis seen macroscopically or microscopically for the above animals in
major crossmatch.
Erythrocytes: Anisocytosis 1+, Polychromasia Occ.
Leukocyte morphology appears normal.
Platelets clumped. Sufficient numbers of platelets seen in film.

VETERINARY COMMENT:
Results marginally decreased from the last bloods, but still no overt anaemia - with low normal RBC
parameters.
The lowered lymphocytes are usually due to stress/ steroids.

She will be on the 10mg and 5 mg dosage for another two weeks before any change pending another blood test.  I am wondering what the next move should be.  I understand that the 5 mg is not a therapeutic dose, so if we moved to 5mg per day, she would basically not be receiving any advantage from the pred?  And the Leflunomide would be providing control of the IMHA - is this correct?  So would the next move be to stop the pred, or would it be better to go to 5 mg every other day?  I find it all quite confusing as I don't fully understand how the meds work.

Thanks Jo

Patricia

[Jo CIMDA]

HI Patricia

The bloods are looking ok. Yes the leflunomide is the primary drug and the prednisolone will be reduced and then withdrawn.  There are several ways to reduce when you are down to a low dose and none are wrong.  It largely depends on whether Sophie needs to come off the preds quickly because of unwanted side effects or her minimal side effects allow you to take it more slowly. 

When a dog is on steroids the part of the adrenal glands that produces cortisol becomes dormant because it is being artificially provided by the preds.    The reason for reducing the pred, as opposed to stopping it abruptly, is to allow the body's own cortisol production to kick in and function normally once again.  If you don't reduce in a controlled manner the dog will become deficient in cortisol, which can be dangerous.  So, yes,  a low dose is not having much therapeutic effect but it does give adrenals the opportunity to start working normally again and many vets will want to go to every other day dosing as soon as they can but, anecdotally, it seems better to get to a low daily dose before going to every other day. 

The most obvious reduction might be to reduce to 5mg a day,  but your vet may also decide to reduce to 10mg every other day.  By going to every other day the adrenals have to start working

Other options:

10mg one day -  2.5mg next
7.5mg one day -  5mg the next
5mg one day  - 2.5mg the next  etc...........................................

I have also known dogs, especially those who have previously relapsed,  to be reduced by 1mg at a time.  It depends on the individual case.

Jo

[dalebrook.bp@gmail.com]

Hello Jo

Sophie is doing really well - allowed off lead exercise now which she is loving.  Latest bloods are looking good:

Serum - Canine Profile 3
Haematology - Cumulative
HA1806696 HA1806208 HA1805802 HA1805483 Units Ref Interval
21/08/2018 6/08/2018 23/07/2018 9/07/2018
SOPHIE
MURDOCH

RBC 5.36 L 5.34 L 5.22 L 5.35 L x10^12/L 5.5 - 8.5
Haemoglobin 131 130 143 138 g/L 120 - 180
HCT/PCV 0.37 0.37 0.37 0.38 L/L 0.37 - 0.55
MCV 69 70 71 71 fl 62 - 74
MCH 24 24 25 26 H pg 20 - 25
MCHC 353 349 354 363 H g/L 320 - 360
WBC 10.2 11.6 12.7 17.1 H x10^9/L 6 - 17
Neutrophils % 93 91 90 93 %
Neutrophils Abs 9.5 10.5 11.4 15.9 H x10^9/L 3 - 11.5
Band Neut % 2 2 %
Band Neut Abs 0.3 0.3 x10^9/L 0 - 0.3
Lymphocytes % 4 2 3 1 %
Lymphocytes Abs 0.4 L 0.2 L 0.4 L 0.2 L x10^9/L 1 - 4.8
Monocytes % 2 5 1 3 %
Monocytes Abs 0.2 0.6 0.1 L 0.5 x10^9/L 0.2 - 1.4
Eosinophils % 1 2 4 1 %
Eosinophils Abs 0.1 0.2 0.5 0.2 x10^9/L 0.1 - 1.3
Platelets 333 x10^9/L 200 - 500
NRBC 1 /100LEU 0 - 2
Jenni Donald BVSc PhD Diplomate ACVP
Veterinary Clinical Pathologist

VETERINARY COMMENT:
Red cell parameters have continued to increase and now the MCV is within normal limits. The latter may reflect red cell
production returning to normal? Also we have lost the white cell response - decreased inflammation or changes to
medication?
Erythrocytes: Erythrocyte morphology appears normal.
Leukocyte morphology appears normal.
Platelets clumped, Platelet numbers normal.
** Thanks for sending a fresh film **

Owner: Murdoch, Patricia & Brent Date Tested: 21/08/2018 11:10
1/49237
Notification:
Phone: 07 827 0412 Fax Number: 6478493023
Page

Chemistry - Cumulative
HA1806696 HA1805802 HA1805138 HA1804620 Units Ref Interval
21/08/2018 23/07/2018 25/06/2018 5/06/2018
SOPHIE
MURDOCH
SOPHIE
MURDOCH SOPHIE SOPHIE
Sodium 150 148 150 151 mmol/L 141 - 153
Potassium 4.7 5.1 4.3 4.3 mmol/L 4 - 5.4
Na K Ratio 31.9 29.0 34.9 35.1 RATIO 27 - 36
Chloride 110 108 109 107 mmol/L 106 - 117
Creatinine 67 59 76 61 umol/L 48 - 109
Urea 4.1 4.7 4.9 5.7 mmol/L 2.5 - 9
Phosphate 1.30 1.40 1.60 1.10 mmol/L 0.92 - 1.82
Cholesterol 5.1 5.1 5.2 5.3 mmol/L 3.27 - 9.82
Total Protein 64 66 66 65 g/L 54 - 74
Albumin 34 35 33 36 g/L 33 - 44
Globulin 30 31 33 29 g/L 19 - 35
A/G Ratio 1.13 1.13 1.00 1.24 RATIO 0.52 - 1.7
Calcium 2.57 2.51 2.54 2.50 mmol/L 2.08 - 2.82
Bilirubin <2.5 <2.5 <2.5 <2.5 umol/L 1 - 3
Alk phos 63 89 H 181 H 103 H IU/L 13 - 87
ALT 66 149 H 319 H 236 H IU/L 23 - 88
AST 40 59 H 62 H 63 H IU/L 18 - 51
CPK 563 H 527 H 401 H 511 H IU/L 74 - 385
Amylase 400 372 371 357 IU/L 329 - 1074
Jenni Donald BVSc PhD Diplomate ACVP
Veterinary Clinical Pathologist
Mildly lipaemic sample which may interfere with some chemistry tests.
VETERINARY COMMENT:
The liver enzymes are now back within normal limits and the mild elevation in CK is likely from the
venepuncture. Her protein levels and other parameters all within normal limits.
Gribbles Veterinary Pathology

They are cumulative results for the last three or four bloods.

The vet wants to cut the 5 mg dose out and just do 10 mg every other day.  He doesn't want us to go back for 4 weeks unless Sophie shows signs that being on every other day isn't suiting her.  I'm not very happy about this - I did suggest doing it more slowly but he didn't want to.  I would be happier to do 10 mg one day and 2.5 mg the next day for two weeks, and then move to 10 mg every other day for the next two weeks.  What would be your comment?  She is still on the same dose of Leflunomide (30 mg per day) at the moment,  and that is remaining the same at this stage.  I'm not quite sure what the protocol is if I decide to do something different from the vet's advice - I guess it is just on my head, but obviously don't want to risk anything for Sophie.

Thanks again, Jo.

Patricia

[Jo CIMDA]

Hi Patricia

I am so pleased that Sophie is doing well and back to enjoying her life again.

I think you know how I feel about a reduction of 10mg one day and nothing the next.  I am not a vet so I can't instruct you on how to reduce Sophie's dose of preds, all I would say is as her liver enzymes have returned to within normal limits, clearly she is coping very well with any side effect of the preds, so you must ask yourself if there is any harm is reducing the preds slower than your vet suggests?   If you do this then it is your informed decision.  If the previous protocol was the same, and she relapsed when she went to every other day dosing, then it is prudent to try a different and perhaps a slower reducing protocol. 

So,  is there any harm in taking the pred dose slower?    -  not as long as she is coping well with side effects of the preds.

What benefit is there in reducing to 10mg on day and a lower dose the other?   -   It is less of a shock to the body to reduce the preds slowly, especially when a dog has been on massive doses of preds for a prolonged period of time.   The body systems need to gradually return to normal.

Is there any harm in reducing the preds to 10mg on day and nothing the next?   -  No, but the adrenal glands will kick in and produce their own cortisol on the day without preds, but they won't produce cortisol on the days that you give 10mg. 

What benefit is there in this method of reduction?  -  I don't know.

Do what your instinct tells you to,  and as long as you know that no harm can come to Sophie then there is nothing wrong with you making the decision.   You won't be the first person to, unbeknown to the vet, tweak the protocol and feel happier and more comfortable about this decision. 

Jo

[dalebrook.bp@gmail.com]

Hi Jo

Thank you for your help - Sophie is now on 10 mg one day and 2.5 mg the next day; I am wondering how to proceed from here. 

It seems to me the next step in a couple of weeks would be to bring the daily doses nearer in amount to each other: for example,
move to 7.5 mg one day and keep at 2.5 mg the next day for say two weeks; 
then 5 mg one day and 2.5 mg the next day for a further two weeks;
and then possibly 2.5 mg per day for two weeks before moving to every other day? 

I have had a look at Michael Day's protocol, and he seems to have the doses much closer in amount each day rather than a larger dose one day and a smaller one the next.  I'm not sure what advantage there would be to have a larger dose one day and a smaller one the next?  Professor Day doesn't move to every other day until the doses are much smaller - eg .25 to .5 mg/kg (in Sophie's case, she is 13 kg, therefore 3.25 mg to 6.5 mg).  I'm not sure if my logic is useful in this case!

The vet doesn't want to see her for 4-6 weeks (rather to my surprise as he has always said in the past that when we change the dose he wanted bloods done after two weeks on a new regime), which would fit in well with taking it down to 2.5 mg per day, if that's what you think it would be good to aim for?

On another topic, I wonder if you think that acupuncture can be helpful for IMHA dogs?

Thanks again Jo,

Kind regards, Patricia

[Jo CIMDA]

Hi Patricia

Anecdotally, better results are achieved when the daily dose is gradually lowered, for example to say 5mg and then start to lower the every other day dose.  When the dose is low, because it is not therapeutic, there are lots of ways to reduce and non are wrong.

Again, anecdotally, more dogs relapse when there is a marked difference in the doses given every other day.  I have heard of numerous variations of how to treat AI disease, and the protocol used, but none compare to the Michael J Day protocol.  It  is as good as it gets, but always one has to take into consideration the individual dog's response to therapy and the degree of disease process/remission.  It has to be tailored to the individual. 

The extract below is taken from a reply I sent to someone the other day.  It may help you make up your own mind on how to move forward. 

Although I like acupuncture and other supportive therapies, I personally wouldn't give acupuncture at this stage of treatment.  Some dogs are anxious and if the procedure causes stress this might cause a relapse of the AI disease. 

Jo


Prednisolone should never be suddenly withdrawn because during treatment it supports the adrenal glands.  As you reduce down to a low, daily or every other day dose, the adrenal glands will naturally resume production of glucocorticoid hormone (cortisol) again.   Glucocorticoid affects every part of the body and when it is given in excess, as is necessary to suppress the immune system and bring IMHA into remission, the whole body has to cope with the side effects so it seems logical in the last stages of the drug regimen to reduce as slowly as the side effects allow and for the transition from an immunosuppressive dose to an anti-inflammatory dose, to adrenal supportive dose, to be as smooth as possible in order to achieve a stable equilibrium - homoeostasis. 

Each dog has to be treated as an individual and when you get down to say, 10mg a day you have lots of options and can reduce as slowly as you like - again depending on how Rider is coping with the side effects. Anecdotally, reducing to a low daily dose seems best before going to every other day.  Below is not a protocol but an idea of options which can be tailored to the individual.  None are wrong because these low doses are not 'therapeutic' they just support the adrenal glands and maintain a balance whilst they become fully active again.

7.5mg once a  day

5mg once a day

5mg one day  - 2.5mg the next

2.5mg once a day

2.5mg every other day

2.5mg every third day..............  then withdraw.

I have also known dogs, especially those who have previously relapsed,  to be reduced by 1mg at a time.  It depends on the individual case.  Some dogs have to remain on a low dose of preds to achieve remission, but most can be weaned off altogether.

[dalebrook.bp@gmail.com]

Hi Jo

I've decided to go with the following (two weeks at each dosage):
10 mg one day, 2.5 mg the next - has been on this for 11 days so far
7.5 mg one day, 2.5 mg the next
5 mg one day, 2.5 mg the next
2.5 mg one day, 2.5 mg the next
2.5 mg every other day
2.5 mg every third day

I assume that after the 2.5 mg every third day for two weeks, we could either stop it, or reduce to 1.25 mg every third day?

Does this look reasonable?

This I'm sure is a silly question, but Sophie is under two vets - the one who has been looking after her right through (who is actually a surgical specialist but has experience of IMHA in the past), and a veterinary specialist from Auckland who visits Hamilton once a week, and who prescribed the Leflunomide.  I think once she is off the prednisone (or the current vet thinks she is, according to his idea of reducing the prednisone) she may just see the Auckland specialist, in which case, do I need to come clean about the way I have been reducing the pred, or will it make no difference to what he decides with the Leflunomide dose?  Sorry to ask silly questions, but I don't want to compromise Sophie's treatment. 

Thanks Jo.

Patricia

[Jo CIMDA]

Hi Patricia

Your proposed protocol looks good but as always you have to monitor Sophie every day to see that this is suiting her.

As said before, when you are down to a low dose there are many different ways to reduce pred, and none are wrong.  If this works well for Sophie then there is no reason why you should or shouldn't mention how you have achieved it, and it won't make any difference to the Leflunomide dose.  This dose is pred is not immunosuppressive.

The Leflunomide is taking over as the primary immunosuppressive drug.

Jo

[dalebrook.bp@gmail.com]

Hello Jo

We are well on the way to reducing the Prednisone, and Sophie is now on 2.5 mg every other day.  In herself she is doing really well, exercising her almost daily (not for too long) and she is pretty much back to her old self (organising me very efficiently!).  However, some time ago - I think late last year or early this year (she relapsed on 28 December last year) she developed a reasonably large area on her lower stomach which was a bit like a mild bruise.  I took her to the vet who checked her over and said she wasn't sure what caused it, but couldn't find anything specifically wrong.  This area has within the last week developed to be much darker (not like a really dark bruise, but darker than a fading bruise) and covering a larger area.  I will try to attach a photo - not sure if my skills are quite good enough!  Is this something that can happen when the Prednisone is reduced, and what causes it.  Her recent bloods were perfect - all within normal limits - done on 2 November although not a full biochem - just TP< ALB< GLO< AGR< BILI< ALP<and ALT.  Is it something she needs checking now, or ok to wait until 23 November when she has her next bloods.  Thanks for your help Jo.  (Sorry, the attachment was too large and I'm not sure how to reduce size.)