Canine Autoimmune Hemolytic Anemia (AIHA & IMHA) - Leflunomide (Arava) for IMAH???

Ruger's doctor called me tonight and she wants to start him on another immunosuppresant because he is not improving? She mentioned cyclosporine but said it is hard on their tummies and expensive so she was thinking about trying leflunomide? I have not read about any dogs on this drug? Anybody have experience with it? THanks!

Jaime Parker

I have been doing the Meisha's Hope Web site for over 11 years now and have heard from thousands of people whose dogs have AHIA/IMHA. In that time I have heard from very few people whose dogs have been on leflunomide. One dog that was on this drug was Watson, the April 1999 Success Story at the Meisha's Hope Web site: http://www.cloudnet.com/~jdickson/archives2.htm At the time Watson was using the drug it was as part of Clincal trials. A few years ago I did heard from a gentlemen who contacted Watson's vet. He told me this vet was no longer using leflunomide and was recommending that other vets no longer use it. If your vet wants to use leflunomide it may be very wise to ask him/her why and what their experience is with this drug as well as what their success rate with it has been in the treatment of AIHA/IMHA. Cyclosporine and Azathioprine do appear to be the drugs of choice for most vets these days when a drug in addition to prednisone is called for.

Joanne MN

Jaime, Leflunomide is classed a DMARD(disease-modifying antirheumatic drug)and is used for severe rheumatoid arthritis and psoriatic arthritis, also organ transplanation. It's not necessary for me to go any further into this description because there are 2 significant and serious potential side effects of this drug that *I think* really rule out using this for a dog that has AIHA. Number one is the risk of very serious liver damage and the second is the possibility for myelosuppression, or suppression of the bone marrow (where blood is made). There certainly can be liver impairment with prednisone, but that is usually reversible once the dose is lowered. It appears that Leflunomide can stay in the body for extremely long periods of time after it has been stopped. I see this as another potential contraindication. And finally, there can be allergic reactions to some of the inert ingredients. I know cyclosporine is expensive, but the nice thing about this drug is that, once the drug reaches efficacy in a week or so, the treatment period can be relatively short and the doses can be lowered, thus lowering the cost quickly. Of course every dog is different, so your experience could be different. Digestive issues can occur with cyclosporine, but most dogs can tolerate it really well without this. And that is pretty much the most serious side effect of this drug. There are a few other very rare side effects, such as a skin problem, but they do subside once the drug is removed. That's exactly why I don't like what I read about Leflunomide, it's going to stay in the body a long time after the doses are stopped. my best patrice

Patrice NYS

It sounds like using the Leflunomide may be a very big mistake. Please don't let your dog start this medication! Cyclosporine is expensive but the results for most of the dogs on this site is excellent. Research some more and encourage your vet, in a very nice way of course, to research also. Print out a lot of this information and provide for your vet. A good majority of vets, not their fault mind you, are not familiar with treating this disease. Check Meisha's website and print out info also and give to your vet. If your vet isn't open to any of this, I would seriously consider finding another vet who is and will work with you on treatments. Good luck.

Mardi Northern Calif

Jaime, My dog Nollaig's experience with this drug was very frightening.Her white cells down went down initially to a very low dangerous level within a few weeks of being on it(Nollaig never had a white cell issue prior to this only low red cell)but then they lowered the dose slightly and her white cells went back up to normal the vets rested on their laurels slightly thinking that she would be ok now in terms of low white cells. BIG MISTAKE... 9 days after her blood test when her white cells were back to normal, Nollaig had to be taken into specialist vet hospital due to a severe case of sickness and diarrhoea, and when they checked her white cells they were 0.1 or somewhere around there- almost non existent.She was immediately taken off leflunomide.Nollaig had nothing to fight the infection in terms of white cells,she was put on very high dose of antibiotics and put into isolation where I was told it was touch and go as septicaemia could set in.Luckily Nollaig is a strong wee beagle who pulled through it but she was in hospital for 2 very long and worrying weeks.The leflunomide never helped her red cell count either whatsoever in fact due to her sickness her red cells fell at faster rate and so not only where her white cells non existent her pcv was about 10% and she needed another blood transfusion too.It took about 6 weeks for her white cells to return to normal after leflunomide stopped. The vet told me that there was not a lot of research behind leflumomide and whether or not it helped in pure red cell aplasia(non regenerative bone marrow) a form of IMHA which Nollaig has but Nollaig had already tried all the usual immunosuppressants...Prednisolone,azathioprine(which she had to be taken off too due to white cell suppression not as bad as leflunomide but still too dangerous for Nollaig),cyclosporine(atopica),danazol, none of hich helped her at all.However I know from this forum that cyclosporine has helped many dogs with this condition.Nollaig never had any problems with cyclosporine, it just didn't help her red cells at all.Also leflunomide is incredibly expensive(over £200 for 2 weeks) much much more than cyclosporine. Anyway if you look back on this forum in the last few months you'll see what drugs and holistic treatments are getting Nollaig better after 7 long months and 5 blood transfusions and pcv dropping continuously to as low as 8%.Or if you want to email me direct or ask any questions, as immunosuppressants were not the answer for Nollaig, her bone marrow needed stimulation as opposed to suppression in her case.The vets can't believe she's getting better as I wouldn't let them give up on her and had to in the end tell them what drugs to put Nollaig on, after great advice from another girl on this forum called Karen, whose beagle Darcy got through this disease not with immunosuppressants either. You need to think very carefully about this leflunomide and remember sometimes the vets are just 'trying out drugs' in case they help but as you can see they can do a lot of harm instead.Cyclosporine should definitely be tried first as a lot more research with this drug and if it doesn't agree with the dog's tummy well you can take dog off it but it won't be as dangerous as leflunomide. Hang in there with Ruger though, and I hope that you make the right decision for him whatever that may be, as long as he gets well that's all that matters. Any questions just ask. Cheers Kathleen and Nollaig

Kathleen North Ayrshire

Jamie, sorry to hear of Ruger's sickness. Has his PCV dropped since yesterday? If it is staying stable at 18 I'ld question why they'ld even want to start another drug. It takes time for the drugs to kick in and when they do (especially the pred) you'll know cause Ruger will start to get his appetite back...and drink more water. It took my Tessy almost a week for these two drugs to kick in and during that time her PCV dropped to 10. She was transfused and her PCV climbed above 20 where it slowly dropped to 18 (approx. a week after starting the drugs). It then leveled off and slowly started to climb. All dogs are different and reaction times vary. If they do decide to add another drug you should really consider the cyclosporine (atopica). I added this to Tessy's med cycle and seen huge improvements...as did many others. If you can afford this drug it would be highly recommended. Talk to the doctors about adding a stomach protectant like pepcid. The main thing for now though should be top get Ruger stable. This MAY take multiples of transfusions to accomplish. Tessy only needed 1 transfusion but others on here have had many more than this. These just buy time for the drugs to kick in. One more quicky here....if you can remember you should always ask for copies of all results (blood, chem, etc). That way you can post results here and it'll make it better for us to help you. I'll keep Ruger in my thoughts and prayers. Johnny & Tessy

Johnny

THanks for all the input. I was also wondering about not starting any more drugs. He has been on pred for 6 days and the azzothiaprine for 2 and his holding steady at 18 so why add more drugs? I think I am going to ask my vet if we can wait to add cyclosporine if his humber start to drop. I am against the leflunomide. Any recommendations on natual things I should try would be much appreciated. I did go buy biopreparation and am going to start that as soon as I can get him home. The dr. did not think the algae supplements help but I am a believer in the more holistic medicines than all these harsh drugs. Thanks again.

Jaime Parker

I would get the cyclosporine started as it takes a few weeks to begin working. The only side effect my dog has had was loose stools not diarrhea, she has been on it for over a year now. Each dog is different though, but I would recommend you try it. Ginger also took the bioprep and I think it did help as her PCV rose 10 points in a months time, which was her biggest jump ever. I have since reduced her dosage of bioprep to 2 a day and her PCV has been holding steady in the mid 40's and we are reducing the cyclosporine very slowly.

Cheryl & Ginger Pineville PA

Jaime, I mentioned on your other post about stomach protectorants, so make sure he is on one. As for cyclo, because of the cost and if you decide to use it, ask for just a short supply, that way if Ruger can't handle it you are not stuck with a months worth of costly pills. YOu can get it filled at Costco cheaper than the vet. I would add milk thistle, its good for protecting and healing the liver. Please Joannes success stories. Macs story from this month, His pvc was holding steady at 19 for some time before a gradual climb. Cheryl and Patrice are right about finding what drugs work, I think I would add the cyclo as reading here the the success so many dogs have had with it. YOu also want to ask if Ruger has regenerative or non-regenerative AIMA. I think they can get an idea by the blood work. Take care Laurie

Laurie CA

Hi Jaime Im so sorry to hear about Ruger - Im pretty much a new person to this board also with my Riley, maltese shihtzu, who has Evans Syndrome, but dealing with IMHA at present - I have taken Riley to an educational veterinary hospital and they have increased the cyclosporine intake from 25mg to 50mg to try and get the PCV up - he is also on prednisone and azathioprine - in the first week his PCV moved up from 29 where it had been for a long time up to 34 - once its in the reference range, so Im told by the vet - we can start to reduce the other medications. Reference range is 37-55, so not too far away hopefully. He has had a blood test to see how the cyclosporine is working in his system - therapeutic level should be 300-400 - the first count Riley had showed 136, next few weeks with the increase showed 435! Hope that helps with something. I know from this board its helpful with the sharing of information. Joanne's site, Meisha's Hope, has some fantastic information.

Silka Melbourne Australia

My Dog Anastasia is on round two for IMHA pure red cell aplasia(non regenerative bone marrow). In round one - she was on the max dose for cyclosporine and prednisone - she was backed down off both drugs after she developed calcifications on her tongue, several skin infections, and lost the tip of her tail (due to a blood clot). This time around, her signs were more obvious and we started at a hematocrit at about 27% - on cyclosporine and prednisone we arrived at 41% within a month. We stayed at the dose for about two months and started to reduce the prednisone dosage slowly with the plan being that she would stay just on the cyclosporine. However, her red blood cell level dropped and is now at about 31% and she is starting to have issues with holding her bladder through the day (no bladder infection) and has become lethargic and seemingly depressed. My vet recommended that we add leflunomide (which the generic is much much cheaper than the brand) But I am concerned with the side effects and that I haven't read anywhere that it has helped... Kathleen from Scotland had written that stimulation was working? I'm wondering what supplements/drugs were used for the stimulation?

Shannon Boston

I am happy to report that Rugers PCV increased form 20 to 25 over the weekend and the dr. said we are headed in the right direction. The disease seems to be slowing down so I hope and pray that by next week it has stopped. The agglutination had slowed enough that they don't feel he needs another medication right now. Yay!!!

jaime Parker

I saw this on the other CIMDA site that Ryan had posted. That is such exciting news, going from 20 to 25. Triple yay for Ruger.

Silka Melbourne Australia

Jaime, that is wonderful news about Ruger! the meds are finally kicking in. ' Thanks for the update Laurie

Laurie CA

bumping this up for darren.

Samantha geelong australia

Hello Jaime, Just checking in to see how Rugers doing? Have a great night...Kelly

Kelly Redding

Ruger had another follow up appointment today. His PCV is holding steady at 30. He is eating and drinking tons but has an infection in his hind paw. We can't figure out what it is from but they started him on an antibiotic. Good news is we are getting to decrease his prednisone dosage. Yay! So far he is hanging in there, starting to act like himself and my husband, kids and I are all so happy!

jaime Parker

Jaime, That's great news..Good luck with the decrease and give him some love from Coco and I....Kelly

Kelly Redding

I am bumping up this thread for Jamie. I personally would NOT use leflunomide for a dog with AIHA. Also Azathioprine should be tapered before discontinuing it. Please read this thread very carefully and talk to your vet about starting cyclosporine instead of leflunomide. MANY, MANY AIHA/IMHA dogs have done very well on cyclosporine.

Joanne MN

So... Ana started Leflunomide before Christmas (along with her cyclosporine and prednisone) due to a failed taper of her prednisone (from pred and cyclosporine) By New Years she was very anemic and was very tender in the belly and Melena (Black sticky BM) and she was brought back into the Vet for a three day stay due to her PVC being down at 14% (which she got a transfusion for!) and bleeding ulcers (due to the prednisone)... It doesn't seem that the Leflunomide did anything before Christmas... I haven't read anywhere the success rate of this drug or side effects in dogs or how long before they typically see results.... Now she's on gastro-protectant and back on the original dose of pred as well as the max dose for leflunomide and still max for cyclosporine. The blood transfusion brought her to 20% and After the first 4 days of all the drugs, she was steady at ~25% I've also started her on the biopreparation to see if that helps... - I find out Friday if she's been maintaining 25% or not.... by looking at her gums it hard to say...

Shannon Boston

Shannon, Was Ana ever on the azathiaprine? Ruger has started the leflunomide but I am going to try and get him switched to cyclosporine tomorrow. He isn't really interested in his food again and I am kind of freaking out. Keep me updated...hope Ana is 25% or higher!!!

jaime parker

Good morning everyone. If you folks are truly interested in leflunomide, I would direct you to the research that was done at UC Davis veterinary school by Dr. Claire Gregory. Dr. Gregory was one of the pioneers in kidney transplants, and was lucky enough to be able to use this drug in an experimental setting (see Watson) but was unable to continue to use the drug therapeutically because it was so cost prohibitive. Please see the article "Leflunomide effectively treats naturally occurring immune-mediated and inflammatory diseases of dogs that are unresponsive to conventional therapy" in Transplant Medicine.(C. R. Gregory, b, A. Stewartb, B. Sturgesb, T. DeManvellea, b, A. Cannonb, T. Ortegab, M. Harbb and R. E. Morrisa). In that study, very few side effects were reported. The liver damage reported in people has not been seen in dogs (though this remains possible). The low white blood cell count has been reported, and we had a case of ITP that would not respond to other drugs (azathioprine, prednisone and cyclosporine, together) that finally responded to leflunomide. He developed a low WBC count, the dose of the drug was lowered and this dog is doing great. Remember that azathioprine also can cause liver failure and it is the standard of care along with prednisone for IAHA. In regards to cyclosporine, there is no evidence nor studies indicating that it does start working in 1 week and based on its mechanism of action we would actually expect it to take at least two weeks to be fully effective. That said, I think anectdotally that it does begin working sooner than 2 weeks. I caution those of you out there that make bold,non scientific statements to people whose animals are in desperate need of help. There are very few veterinarians that even know leflunomide exists, and I suspect most of those prescribing it have good reason to. I hope all of your animals are well.

Alanna Davis

Alanna, I only was able to find this: http://www.ncbi.nlm.nih.gov/pubmed/9865328 on the article you mentioned. Could you please point us to more info on that article? Thank You!

Joanne MN

Hi Joanne, I wish that article was free, but I guess it's not. The article is basically a review of the cases that various doctors at UC Davis used leflunomide for. It was when they had the drug for free. They used it for a wide variety of autoimmune diseases that were otherwise either unresponsive to conventional therapy or the patients were having unacceptable side effects to conventional therapy (usually prednisone and azathioprine). For IMHA, they had 6 or 7 dogs total, and all but one responded very favorably to the drug. They also sited cases of ITP, GME (an inflammatory condition of the brain), immune-mediated polyarthritis and systemic lupus. For the IMHA group, the dog that did not respond actually had myelofibrosis (scarring of the bone marrow). For all dogs studied (I think Watson was in this group), side effects were rare and included decreased appetite (2 dogs), diarrhea(I think one dog) and three dogs with suspected GI hemorrhage - though they were also on prednisone at the time. There have been other studies in canine renal transplant models that have shown myelosuppression (bone marrow suppression) at very high doses. I have also found, anectdotally from VIN, that epistaxis with normal platelet counts has been reported though this seems to clear up without further consequence. I didn't mean to intrude on your site, but while researching leflunomide myself I stumble upon this thread and felt this was important information to convey. Jaime, how is Ruger doing? I certainly hope he is holding up. I agree with Joanne that cyclosporine is a great choice for him and have many, many successes with that drug with very few side effects. Is there a reason your veterinarian gave for why they didn't want to prescribe it?

Alanna Davis

Alanna, I appreciate your positive info on leflunomide. Ruger's vet was actually at UC Davis during these studies and this is why she is a fan of it. The patent is off of it now and it is relatively cheap in comparison to cyclosporine with few side effects. The reason we have not done the cyclosporine is that for a dog or Ruger's size it costs about $400-$600 per month. In addition, the blood test to test the levels of it in his system are about $100 each time. We have already spent $8000. Not that I want $ to be my final determination but I have 2 young children to think about and I can't justify spending thoudands on cyclosporine when leflunomide is an option. If Ruger responds badly to the leflunomide then we will probably have to do the cyclosporine. Update on Ruger is...1 week on leflunomide and doing well. He is experiencing some decrease in appetite but still managed to gain 2 kg this week so that is good. His PCV holding steady at 32. His bilirubin is down to 2.5 but his liver values remain elevated telling us it is from the predisone and not the azzathiaprine as we were worried about so that is good because now we can go back to azzathiaprine if Ruger has any bad effects from the leflunomide. I am hoping and praying that this week the disease STOPS and we can get him off some of the prednisone. I am aware that cyclosporine may be what he needs but I am trying this other first. My 3 year old was in the hospital this week for a respitory virus and that is going to cost a lot of $$$ as well so that kind of put things in perspective for me. The leflunomide has to work!!!!!!!!!

jaime parker

That's great news Jaime! Good luck with Ruger!

Alanna Davis

Jaimie, thanks for your comment! It sounds like Ruger is doing better and I hope he continues to get better (without losing his appetite)And I hope your child is doing better. If I could give you a hug, I would... this time can't be easy for you.... As for Ana, Well - her PVC dropped from the 25% to 16% - the Vet upped her Prednisone (he's leery due to the fact that she didn't tolerate it well the last time with the skin infections and calcifications) yet for the 45# dog we are now on 100mg of Cyclosporine 2X daily, 40mg of leflunomide 2x daily, and 30mg of prednisone 1x daily, with a regimen of gastroprotectants.... I will be checking back in with the vet this week to see if the ulcers she had earlier are still causing her to bleed into her intestine - but now she has diarrhea and is bleeding due to the irritation....She had been tested for bone cancer the first go round and x-rayed and ultrasounded - all looking for cancer just in case - and nothing - this time she's also had an Ultrasound abdomen and her heart and everything was good... How can immunosuppessant treatment work and then stop working? My Vet says that she could develop cancer due to the body's inability to fight off abnormal cells...I am also feeling the financial pain and the first time around with medication total was about $10,000 and this time around I'm getting near $5,000 and I'm reaching my limit of credit... its financially stressful and its emotionally stressful - I wish there was something else I could do... but the outlook is getting to be poor. Alanna mentioned myelofibrosis... I read a little on the net.... Ana has non-regenerative IMHA - when her body attacks the bone marrow and in particular the cites that produce red blood cells, are they permanently destroyed? of does the body regenerate those cells as well? or does it form this scar tissue? and can this scar tissue keep growing? Could that be a reason for the immunosuppressant treatment to stop working? that there aren't enough cites anymore to produce red blood cells?

Shannon Boston

Sadly - Ana lost her battle with IMHA. She somehow stopped responding to the treatment although was very immuno supressed and wound up with a widespread infection on top of being very anemic... Thanks to everyone on this site and good luck to all of you.

Shannon Boston

Shannon, I am very sad to hear this about Ana. You tried so very hard to win this battle. My dog went through a similar serious condition in 2007. It was touch and go for many months. The risk of a general systemic infection was great. His marrow was essentially devoid of any cells and the specialist gave us little hope. These cases are very very difficult. I hope you will understand this and be comforted by the knowledge that sometimes we can try so hard and still find want we want just out of reach. I lived many mornings and many nights facing the possibility of success or the terrifying chance of failure. For the rest of your life, Ana's spirit will live on in you. People around you will notice something special and wonderful about you and may never know about her. Please accept my deepest condolences. Patrice

Patrice NYS

Dear Shannon Im so very sorry to hear about Anastasia - please accept my sincerest condolences. It seems to me you did everything you could, and then some. I will never understand this illness. Thinking of you Silka

Silka Melbourne Australia

Shannon, I am so sorry to hear that you have lost your Anastasia. I am sure she knew how much love you had for her. It is so heartbreaking to lose a best friend so please know that it does get better and one day you'll rememeber her with a light heart...Kelly

Kelly Redding

Shannon, I'm so sorry to hear of your loss. My sympathies and heartfelt condolences to you during this tough time. Run Free Ana. Johnny & Tessy

Johnny

Shannon, I am so sorry for your loss. Cherish the good memories of Ana and may they heal your broken heart. With sincere condolences, Brigitte

Brigitte BC Canada

I am very sorry your pup, Ana, passed. She fought hard and you were with her doing your best. All our pups are together playing and pain free. My heart goes out to you. Take care.

Mardi Northern Calif

Shannon - I'm so sorry to hear you lost Ana - It's so tough having gone through this once already and having to begin again. You are in my thoughts and I know Ana thanks you for the love and care she received while she was with you. She'll always be with you in spirit.

Lisa TX

Shannon Please accept my deepest condolences in the loss of your beloved Ana. Feel comfort in knowing that you did everything you could do for her and sometimes they just can't be saved. I pray for strength and courage to help get you through this difficult time. Godspeed Ana you have earned your wings. Cheryl & Ginger

Cheryl & Ginger Pineville PA

This thread was discussed between 18/12/2009 and 09/02/2010

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