Relapsing on Leflunomide

[Kirsty.Stick]

Hi all,

We have recently experienced two relapses with Cali, our 2 year old Sprollie.

Just before last Christmas we were getting down to 2.5mg pred once daily, unfortunately cali relapsed on this dose, possibley because she picked up a bug going around in her dog walking group and her immune system just went in to over drive. Following this she was started on 20mg Leflunomide with 17.5mg pred on a 4 week tapering scheme. We got off the pred well enough and she seemed to be doing well then out of no where she relapsed in February again whilst solely on 20mg Leflunomide once a day. Our local vets reintroduced the pred in order to control the relapse quickly until we went to see the referral vets, on review the referral vets have increased the Leflunomide to 30mg once a day which is a mid range dose for her weight of 17.8kg. They want to come off pred again and remain on the Leflunomide which will also taper over time but I have little faith in this drug based on the previous relapse.

Anyone else's experience with it would be welcome!

Kirsty and Cali 🐾

[Jo CIMDA]

Hi Kirsty

I am sorry Cali has relapsed. Anecdotally, Leflunomide has mixed success. I have known it to suit a dog very well and I have also known it to be ineffective.  It is often used as a combination therapy for immune mediated polyarthritis.   I can't remember what AI disease Cali has but the usual mainstay of treatment when a relapse occurs is prednisolone given in immunosuppressive doses for 10-28 days and then reduced over a period of time and this is given with or without another immunosuppressive drug.  See the guide below.

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.

"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.

There might be a very good reason why Cali isn't prescribed a full immunosuppressive dose of prednisolone but if she can tolerate the correct dose of prednisolone then it might give a better chance of achieving long term remission than with leflunomide. 

You could ask the specialist why Cali isn't on a drug protocol like the one above and if the answer is simply a choice of drug then ask if the mainstay of treatment can be pred. You have nothing to lose by asking.

I do hope you see an improvement very soon.

Jo
 

[Kirsty.Stick]

Hi Jo,

Thankyou for such a detailed reply.

Cali has IMPA, it seems that with each relapse she develops worse symtoms, she has begun retching and gagging before the diarrhoea now which did throw everyone off the scent in December thinking she had a blockage but it was in fact the IMPA. She is currently on a pred tapper similar to the one you describe, she's on 1mg/kg every 24 hours though and that does sustain her very well with manageable side effects. We get the impression neither our local vet or referral vets want to rely on the pred long term again although we have discussed this with them as she is a much happier dog and we feel her quality of, how ever long or short, would be best on pred.
The current plan is to slowly reduce the pred every 4-6 weeks by a minimal increment until weaned and hope the Leflunomide holds the IMPA .

I know part of the reason to come off pred eventually is to allow us to spay Cali as her first season came at nearly 2 years old and was followed by a phantom pregnancy, there are worries about infection risks with recurrent phantom pregnancies as she has already shown fluid/gas on the uterus in abdominal scans done to investigate the retching in December. Also there are suspicions that the relapses may well be linked to the season and phantom pregnancy as all happened within a period of months. We also spent 9 months on pred last year and feel we were so unlucky to relapse on what seemed like nearly the end of the treatment.

I just have little faith in the Leflunomide after February's relapse and can't see it holding the IMPA without the pred, the lower dose pred seems much more effective based on her reduction in symptoms on a borderline immunosuppressive dose after the  relapse in Feb.

Kirsty

[Jo CIMDA]

Hi Kirsty

The problem you may have is if the leflunomide isn't having the desired effect then just putting Cali on pred @ 1mg/kg/24hrs will not be sufficient to suppress the immune system enough for it to return to normal function, without circulating autoantibodies that are targeted against the synovial fluid in the joints, and therefore it might be only tempered so when you get to a low does the disease becomes active again because true remission hasn't been achieved.   

IMPA commonly relapses in the early years, especially when the preds have been lowered significantly and near the end of the treatment regimen,  but IMPA does carry an excellent prognosis once it has been brought under control and most dogs can lead a normal life, without drugs, when true remission is achieved. 

I appreciate that they want to spay Cali but if the medication she is on is not going to bring the IMPA into remission then you can't spay her anyway.  Perhaps the control of IMPA and the target of  remission should be the priority and not think about how you are going to deal with spaying in future.  If Cali can tolerate the usual immunosuppressive dose of preds (1mg/kg/12hrs) then perhaps this is the best way forward.  Make sure she is having a gastroprotectant.  She will not have a season while she is on high doses of preds. 

I know this is disappointing for you.  If you are not happy then perhaps you can seek a second opinion. 

Jo

[Kirsty.Stick]

Hi Jo

I see your point about true remission, I wonder if this scenario contributed to her relapse in feb following the initial one in December where we only used 1mg/kg/24hrs pred to begin with.

I think we will give the Leflunomide a try at this higher dose along the same principle of the higher dose pred but if she relapses again I think we will push for a full pred regimen again rather than staying on the Leflunomide.

Spaying her would be good but it does come second to the IMPA treatment.

Thankyou for all your advice, hopefully we will have some good news to share over the coming months!

Kirsty