Cornell Feline Health Center: Feline Infectious Peritonitis (FIP) treatment in the USA

greetings from itha everybody my name is Bruce cornr and I'm the director of the Cornell felon Health Center and thank you for joining us for a very special webinar today before I get to the topic and introduce our very esteemed speaker I just want to run through a couple of logistics um that have to do with how how things will run today um if you have questions please enter them in the Q&A function we'll review them and try to get through as many as we can at the end of Dr Cogan's presentation of course we're going likely to have hundreds of uh attendees so please understand if we can't get to all the questions but we'll do our best to get to a good smattering of them and a nice kind of a distribution of them a friendly reminder for those attending the webinar who want to receive New York State continuing education credits you must be logged in for the entire presentation once we end the webinar there'll be a popup with a survey that must be completed to confirm New York State continuing education credits if you miss that that's okay there'll be a reminding a reminder sent to you via email two days after the webinar those of you who are not interested in credit we welcome your feedback regarding our feline Health programming as well so now that we're done with the logistics um we're very excited to have Dr Sally cogins talked to us today about feline infectious peritonitis treatment in the United States you know I have to say I've been here for about 12 years and FIP is one of those thing perhaps the most commonly requested topic for us to provide guidance on and I have to say that uh until quite recently this was considered to be a disease that was almost routinely fatal so in my view and probably Dr cogins would agree with me uh the development of these new compounds for treatment of this uh really previously well still a devast disease but routinely fatal disease is one of the really big Paradigm shifts in veterinary medicine since I've been a veterinarian and I graduated in 1992 so we're really excited to have Dr kogin who's really one of the foremost experts on the treatment of cats with this new series of drugs so a little bit about Dr kogin uh Dr kogin graduate graduated from the University of Sydney Australia in 2007 and has been a feline only clinician since 2010 she attained membership sh in filon medicine with the Australia and New Zealand College of veterinary science in 2012 was the director at the Cat Clinic Melbourne an examiner with thez CVS and tutors for the center for veterinary education since 2020 Sally has been completing a phc investigating antiviral therapies for FIP and with that phc is imminent um where she conducted a national prospective uh study utilizing REM dise and GS 441524 characterize the invitro and invivo pharmacokinetics of REM dise in cats with FIP co-authored a retrospective collaborative study assessing treatment outcomes of 307 cats treated with r dise and GS 441524 and has ongoing research collaboration with within the United States UK Germany and New Zealand Sally also continues to practice clinically one day a week at Everet in Melbourne Australia so clearly a a wonderfully talented and experienced person who can speak in the clinical realm research realm and we're really quite happy and really honored to have her with us today Sally thank you so much and we really look forward to hearing what you have to teach us please take it away thank you so much Bruce that's very kind and yeah I'm very excited to to be back speaking for um the Fain Health Center this is such an exciting space and it's become even more exciting for people based in the US uh in recent months with sort of a more legal route now to accessing some of these drugs which has been a real barrier um and Still Remains a big barrier in in several parts of the globe now I guess the primary objective for me for this talk um I I'm aware that not all of attendees are going to be uh registered dbms that are treating in clinical practice um but for those of you that are I really want to try and make this as practical and help upskill you so that you feel really confident treating these cats in practice um and so there are some quizzes throughout this webinar and they are probably a little bit more directed towards the vets in the room but everyone's welcome to um to participate if they wish firstly my disclosures I have um delivered a number of webinars like I'm doing tonight oh yeah tonight your time this morning my time um for honoraria on the topic of FIP treatment and um I guess I just want to disclose that no external group has had any influence on my research or the content of my talks uh I will however be discussing the off Lael use of ram des and the non FDA approved use of gs-441524 mol perir eid1 1931 paxed and mequin for the US in cats with FIP a bit of a a rough outline of what hoping to tick off today um essentially I'm just diving straight into the treatment aspect of this I'm not going to be discussing uh the evolution of how how this came to be that we got access to these drugs I'm not going to be discussing how we go through diagnosis of FIP but I will direct you to some additional webinar resources at the end of this talk for that um but the key antivirals and expected response rates is what I'm going to spend the most time discussing today and the current treatment protocols that are being implemented we're then going to go through the recommended monitoring and expected response to therapy um and when we need to be considering dose adjustments I then want to go through troubleshooting refractory FIP cases and introdu you to those additional antivirals and then I'm going to do some case examples uh to finish hopefully if we have time but I think the elephant in the room and I just want to uh sort of run through this from the GetGo is still around the legal the legality of compounded GS 441524 in the US this slide is adapted from a wonderful colleague of mine Samantha Evans who co-presented a webinar with me um recently on this topic uh and I'm I'm borrowing this from her because it was it was well uh constructed and to the point and essentially compounding of GS 441524 is not legal but but it is expressly allow by the FDA under the DFI number 256s enforcement discretion now the FDA announced their position on the use of compounded GS 441524 to treat FIP and explicitly stated that they do not intend to enforce new animal drug approval requirements for products compounded from GS 441524 GS is under review as a substance approved for office stock um but whilst it's under that review process it can be ordered and kept as offer stock in the meantime except for the following states if you are residing in those following states that doesn't mean that you can't access GS 441524 through compounding um Stokes compounding pharmacy it just means you can't have it pre sitting on your Pharmacy shelf you need to order it for the individual patient GS 441524 remains under patent until 2029 but there have been no efforts to stop compounding pharmacies from producing this in other countries for the veterinary market so essentially it is legal for a DVM in the US to prescribe GS 441524 to a c with suspected FIP through a licensed compounding pharmacy now I just want to take a little um pulse on the room um or or the attendees that are here live if you pull out your smartphones and scan this QR code I'm really hopeful that this quiz will work I always get nervous introducing Tech into my talks um but if you can all just sort of pull that up and just start um entering in which countries you're tuning in from I'm sort of assuming most of you are from the United States um and I just wanted to make sure that I I'm not surprised to see we've got um Canada but I'm just interested in other parts of the globe that may be tuning in because the application of this is quite independent of um you know exactly where you're you're tuning in from okay great so yeah a lot um from the US as expected but um we we're definitely seeing Canada Brazil Chile Australia hello fellow Australians um Germany cool all right so it's um it's a bit of an international mix excellent let me see if I can move so this is sort of a bit of a a map that I created in the last couple of months of just who can get GS from where um given the majority of attendees are probably going to be tuning in from the US uh Stokes Pharmacy is the compounding pharmacy that is doing GS 441524 tablets and they are using the exact same formulation as B compounding so B are who kind of started all of this uh in Australia back at the end of 2020 we got access to compounded REM Desir as a parental formulation and then um Ral GS 441524 the UK quickly followed because boa have operations in Australia and the UK and from the UK Botha can export to a number of different countries which are sort of starred here in the purple the darker purple stars for Germany and Switzerland um it they do have access to B stock but it's for research purposes only and for our New Zealand colleagues they get Ram Desir from Optimus healthc care so it's it's gradually increasing the number of countries that have access to um well formulated compounded versions of these drugs which is really encouraging I've got another quiz for you all if you can keep your smartphones out and it may just flick if you keep the browser open it may just flick to the next one but for primarily the clinicians that are in attendance I just want to know who right now would feel confident treating a case of FIP if you were presented with something tomorrow or you know tonight who is going to have some clue of where to start okay great so I'm glad there's um people that are not confident are in attendance because hopefully um I can help increase your confidence uh it looks like there's sort of a little a few that definitely have some experience which is amazing um awesome okay great thank you all for your contributions that just helps me know where pitch this a little bit better as we move through so with the um with the drugs that I want to introduce at the Forefront of all of this are these two compounds Ram Desir and GS 441524 and it's important to recognize that these drugs are linked essentially REM Desir is the prodrug it's a nucleotide prodrug of GS which is the core nuclear side when we give REM dese to a cat it gets turned into GS or we can just give straight GS to a cat and we get GS but ultimately that GS is then further hydrolized into an active triphosphate and it's the active triphosphate that is the actual antiviral component um but it's just important to be aware that if we give one we sort of get the same result is is essentially um the the methodology behind how some of these protocols work as well and I guess just to introduce as well there's another pairing um which I will touch on briefly which is mol p and eid1 31 it's a similar concept where MMA perier is the pro drug and the eid1 1931 is the core nuclear side now these are just some recent Publications that have purely used the compounded formulations and this talk I am very much focusing on the use of the compounded formulations and off label access to human drugs I will not be discussing um the the unlicensed formulations which are defin Ely still out there and may still be your only Avenue depending on parts of um the world and the US that you're you're sort of coming in from but ultimately in terms of the expected survival rates that we can um achieve with these drugs our prospective study from the University of Sydney we achieved an 86% survival to 6 months this was the retrospective collaboration that um the amazing Sam Taylor sort of headed up uh wrangling 307 retrospective histories from between mainly the U um the Australia and the UK uh we achieved 84.4% survival in that study and then another uh retrospective study from the Royal veteranary College achieved 81.3% there are prospectives underway in Europe um mainly with Munich and Switzerland um so Munich Germany and Zurich Switzerland but also the University of burn have a prospective or using B formulations uh and there was a recent publication from our colleagues at the University of Munich uh it's an exciting new publication looking at shorter duration of treatment comparing 6 weeks to 12 weeks of therapy their overall survival rate was 95% um but just a little caveat that um the selection of those cases was a little bit biased towards the less severe forms of FIP whereas these other Publications included Mar fed animals because we had uh parental REM dese so we could give an IV whereas the Munich study they were only studying oral and so animals needed to have a competent swallow reflex and and to be um in a sound enough state to be able to receive oral medications with regards to um our study here at the University of Sydney I have updated survival data uh for those cats and we achieved 83% overall survival to 18 months a lot of these cats now have just hit their three-year long-term survival Mark and I'm still in contact with a lot of their owners and receive delightful photos of fat happy cats which always brightens my day the one cat that died uh after the six-month Mark uh likely was due to neurologic complications of congenital pituitary dwarfism but we were unable to do a postmortem in that animal so I couldn't 100% exclude FIP being involved it was considered unlikely um I think another key statistic that is helpful to me as a clinician though is that the majority of cats that we start on treatment in terms of where we see that mortality it tends to happen very early on in the course of treatment and whether this is due to the fact that their disease is just too severe to reverse or we need to optimize how we're managing these patients which again is why it's so imperative that vets are driving the the treatment of these diseases and that we have these cats in our Hospital environments when they need to be if your cat survives for the first 48 hours then the 18mon survival um percentage goes up to 92% so in terms of how um I the clinician go about presenting the enormous amount of literature to a client who I um you know am faced within in private practice essentially my uh my sort of speech that I will go through with them is that FIP is a disease that historically carries a near 100% mortality rate the overall survival rates following treatment with these new antiviral drugs across the literature is between 77 and 96% of cats are going to survive and although we've made enormous progress we do still need to let our owners know that we don't win in all instances and unfortunately we do still see on average about 15% of cats that may still die of this disease but if their cats survive the first few days of treatment then their long-term survival chances go up enormously and we're looking at more like 92% survival so this is the current summary of um treatment protocols with the use of REM dese and GS 441524 um this uh all these slides will be emailed to attendees as a PDF after the talk so don't feel like you've got to randomly scribble down all of these things you're welcome to take photos or screenshots as I go though I don't have any problems with that this changes regularly it's stayed the same for the last couple of months but um it's really important to keep referring back to the most recent presentations because we're having literature published in this space on a weekly basis and there's some much bigger prospectives that are drawing to completion and are in the pipeline for publication that's going to continue to modify and adapt how we're approaching treatment for this disease But ultimately whether you're giving rem dese or you're giving GS we use the same dose rate um the main distinguishing thing that you need to establish as a clinician when you're trying to determine the dose rate is going to be whether or not these patients have opic or neurologic involvement because if they're plain effusive cases or dry um cases so granulomas and other tissues that not Opthalmic or neurologic then we're generally treating them with the same dose these days which is 15 Mig per K per day if I'm giving that as parental REM dese I do that once a day as a slow CRI and I'll discuss that in more detail in a second um if I'm doing um oral GS then you can look at doing that as a divided dose um there are certainly some uh evidences suggest that we may have higher 24-hour plasma concent ations or maintained at a higher level over 24 hours if we split the dose the thing that's still lacking for me though is firm evidence that this is a plasma concentration dependent drug um so we've been sort of doing some therapeutic drug monitoring stuff and there's a lot of variation with cats but I can't actually correlate that variation with outcome um we're looking at doing some population pharmacokinetics but there's another amazing group over in Edinburgh that are doing work in this space and I'm really really excited to see um what they what they eventually publish um but for now for me given that pretty much all of the Publications to date have used Sid dosing for effusive and um and non-neurologic dry cases and the the current sort of treatment duration is 84 days splitting the Dos is essentially asking our owners to double the frequency of administration and I think compliance can start to become an issue depending on the temper of the cat um so I'm very happy doing Sid dosing but sometimes to troubleshoot I will split the dose and I'll talk you through that um subsequently uh with neurologic cases though I do generally divide those um from the start so it's 20 Mig per K per day of oral GS but I will generally administer that as 10 Mig per k b rounded up to the nearest quarter tablet um I think it's important to highlight that most cases now we do treat with rlgs from day one when you read the literature A lot of the protocols that were first published including my own um protocol advocated for using IV Ram Des AE for the first few days and then transitioning them to either subcutaneous RAM dese and then onto oral GS or then straight to oral GS really that's because of how the timeline of drug availability evolved and where our ethics applications were up to at the time so we only had REM Des for the first 12 months and my ethics application was written that all these cats had to start with REM deser as we got access to Legal GS we had ethics allowance for me to continue to monitor cats if their vet and their owner elected to transition them onto tablets and as we built confidence with um cats outside of the prospective study we we rapidly decreased the duration of subcutaneous um administration of RAM dese and ultimately just move to straight giving these cats tablets from day one as long as they're in a well enough state to be able to swallow a tablet and not needing really intensive Hospital support so although the literature promotes IV Administration first I touchwood I don't remember the last time I used IV REM dese it's definitely been more than 12 months because we're able to access oral really rapidly and we're um very proactive with um sort of confirming our diagnosis and starting treatment I'm not seeing these really endstage cats anymore either which is really encouraging um so GS if you haven't seen it uh these products are sorry these photos are courtesy of Stokes Pharmacy this is essentially what it's going to look like if you um write a prescription for compounded GS in the US these are a 50 milligram quad scored tuner flavored tablet we still recommend giving these fasted I generally withhold food for one to two hours before for administration but if these are teeny little kittens it's definitely more toward the hour Mark um it's okay though to give this with a tablespoon of wet food or one of those little creamy churu treats to help wash it down and to make it a positive experience for the cat and then I'll generally Reserve uh giving them a full meal until about 30 minutes after we do always want to round up to the nearest quarter tablets so that cats continue to grow into their dose and not grow out of their dose um these cats will often put on a lot of weight over the course of treatment um as we'll be familiar a lot of FIP presents in our younger cats although we do definitely see it in cats of any age um but most cats will put on on average about a kilo of body weight over 12 weeks so we need to be accounting for the fact that they may gain a considerable chunk of weight between reviews and it's important that we are rounding up and letting them grow into that dose boa who Supply Australia and the UK and pretty the rest of the world that's not um the US they do also do a tuna flavored oral suspension which Stokes are definitely in the process of um of hopefully launching imminently um so you will be able to titrate doses a little bit uh more finely with the oral suspension which is really helpful if you are faced with cats that are less than 2 kilos the quarter tablet increments do become quite a big jump in dose rate whereas or suspension gives you more flexibility there and um this again um is a slide that I credit to another amazing colleague Samantha Taylor uh just reminding us to make this uh think about compliance and help our owners help these cats so don't be afraid to use these creamy treats we really do need to try and invest time in making um medication time a positive uh part of the day for our cats and our owners um and these are just two cats that um this cat literally on the left just licks the tablet with the churu on it because he's a ginger um this little kitty on the right was a little bit more um tricky these owners were actually crushing the tablet into the creamy treat and then syringing it back into an empty foil wrapper so that it looks to the cat like it's just a treat um however you need to do it to make it um feasible for your owners I think it's really important that we're investing that time and sometimes it is about um you know scheduling time to to your owners to be um upskilling them on how to use pill poppers or or you know oral medicating um their cats when it comes to Ram dese I I probably will fly through this a little bit quickly but again you can refer to the slides ultimately um vlar is the the formulation that's available in the US this is used for debilitated patients that don't have a swallow reflex so essentially um given that it's a little bit harder to come by in the US oral is going to be your main state of therapy but if you do have a really obtunded debilitated animal um there is an IV option that's FDA approved for human use in covid-19 patients therefore and you can use it off label as a veterinarian so you can write a script for this as a DVM through off label use in your cats the issue is it can be quite difficult to obtain and it can also be very expensive um ultimately because this is a an IV formulation it's not something you're going to find at your corner drugstore um these are generally if you're going to find these vs they'll be Ines associated with human hospitals or teaching hospitals uh and it's not something that every vet is able to access from what I've heard I'm just communicating with dbms over in the US so I think it's really important to anticipate that this could be a presentation that you might need to deal with and it would be really good to reach out to your local pharmacies to figure out whether anyone does actually stock these vials and what sort of cost you're looking at so that you're prepared but in terms of how we prepare um vlar it comes as a powder that needs to be reconstituted in the vial initially but then further diluted in sodium chloride or 5% dextrose if you follow the manufacturer's recommendation um the final concentration should be between 1 to 2 Mig per Mill um I do say from a cat perspective you probably want to aim for that to PR final concentration purely because of volume overload being a potential issue um when we're looking to then administer this over 30 minutes to 2 hours now um I did note a little discrepancy and I just want to flag that with you all in the original um slide that I showed with the summary of dose rates down the bottom it will say that you can give REM dese over 20 to 30 minutes IV that is if you're using the Bova REM dese if you are using vlar um we recommend you have to do this sort of pre-dilution Step but um the general recommendation now is to give it between 30 minutes and 2 hours anaphylaxis has been reported in humans following rapid IV boluses which is where um you know we've kind of followed suit that we're not in a rush to jam this into these animals I however am not aware of any cats um experiencing anaphylactic reactions and when we were first doing our prospective study and I was doing the phic kinetics on these cats I was administering these boluses over 30 seconds to 60 seconds and we didn't have any adverse outcomes but I'm not in a rush so generally I'm setting this up as a continuous rate infusion for my patients um I just going to run you through a case example on you know if if you are in practice and you're presented with a really debilitated animal um this is such a debilitated animal this is Milo who was one of my prospective kitties he had a non-a usive FIP or dry FIP without any Opthalmic or neurologic signs um he was developing hypo aoic Rim signs on both of his kidneys and had enlarg meic lymph nodes we did aspirates of his kidney um and it was coronavirus PCR positive and also immunocytochemistry positive to confirm his diagnosis but he also had a lot of those Hallmark signs on biochemistry of hypog globul anemia hyp rub anemia and nonregenerative anemia all of the sort of waxing and waning pyrexia and weight loss but he was 3 .8 kilos um at the time of diagnosis and so for a dry FIP case with no optho or neuros signs we were going to administer him a 15 Mig per Sid IV Ram Desir dose which calculates out to be 57 milligrams now if you're doing that 2 Mig perm final suspension of um or final dilution of your resuspended RAM deser solution that equates to 28.5 Ms and if you're going to administer that over 2 hours that's 1.5 maintenance rates for that animal um and that's again where I think it's really important that you're um calculating ahead and then looking back at final concentrations final volumes sorry of the drug that you're administering relative to your patient and making sure that you're delivering it in a time that's not going to encourage fluid overload um Milo responded really well after the first few doses of IV RAM dese and so we then switched Milo onto oral GS 441524 tablets so if we now want to transition this cut onto tablets we do the same calculation because we're going to use the same dose rate of GS so 15 Mig per KCK which is the 57 milligrams um because these are 50 milligram tablets and we need to round up to the nearest quarter tablet um we elected to give Milo one and a quarter tablets which equals 62.5 milligrams so that he's growing into that dose so this is him when he um sort of first went home after having his few doses IV and he' started eating his pyrexia had broken he was starting to look more alert and and be able to move around the cage freely um skipping ahead a few weeks so at week six Milo had gained um nearly a kilo so sort of 800 gram of body weight it was 4.6 kilos which meant that 15 Mig per Ki we needed to be aiming for 69 milligrams which means we bumped him up to one and a half tablets of GS go to Weight 10 where he now weighed 5.2 kilos so he needs 78 migrs we're now going to give him 1 and 3/4 tablets and then this is Milo two and a half years later who is whopping 6.42 kilos and remains quite chunky to this day um but this is just an example of how important it is to be um monitoring that weight creep and making sure that you're adjusting the amount being delivered to continue to meet that dose rate requirement things that I avoid with REM Desir and GS um the first thing is I don't like my CS to drop below 15 Mig per K per day at any point anymore we always want to estimate up initially I set that bar at 10 Mig per K but um we were still seeing the occasional case with refractory um FIP or or sort of breakthrough symptoms on 10 Mig per K per day so generally the standard dose seems to be moving towards 15 Mig per K per day and that's certainly um you know what was used in the munic study that I've referenced we don't want to adjust the dose down with weight drops and this is this is how we approach things there may be um some different methodologies out there but essentially particularly with our fusive cases it's quite common that they will drop weight when they resorb their affusion I'll show you a graph of that in a minute essentially if I start them on that weight and they um are resorbing their fusion and and get a bit lighter for a while tend to hold steady on the same amount being administered and then just wait for them to start to regain healthy body weight for me to adjust up from there I've revised this statement to say caution stopping treatment before 12 weeks historically I've said do not stop um treatment before 12 weeks until we have more information I mentioned pardon me that um we do have a new publication that's emerged from our colleagues at Munich um who have done a prospective randomized comparing six weeks of treatment to 12 weeks of treatment with the 20 cats in each group that has now been published and it's really exciting to see that um out in in um published literature the thing that I will say is um I mentioned before there there is probably a slight bias in that population to be um recruiting less severe cases and um personally I have definitely seen cats come out of remission with shorter duration of treatment where we've been limited by the the finances of the owner so I I am still generally going to be aiming for 12 weeks but the main thing for me is that I really want to make sure that all referable signs of FIP so their biochemical changes their physical exam changes have all resolved for at least two weeks before I'm going to discontinue the antiviral so if you do have a cost constrained donor or a patient that's just responded so well and bounc back to pretty much all normal parameters within 2 to 4 weeks absolutely I'm now going to have a bit more confidence to think maybe we can stop at six weeks but I I'm I'm reticent to say that all cats can just be treated with six weeks because we we have seen cats fall through the gaps even with extended treatment trials you want to avoid using continued corticosteroids beyond the first one to two weeks if you can and the main caveat to that would be uh immune mediated hem anemia that can sometimes present secondary to FIP as a as a complication those cats often will need longer duration of corticosteroids but in general most of the inflammatory signs that we see that necessitate corticosteroids like uiis um in our ocular presentations or um sort of depress mation in neurologic presentations most of th those cuts should be responding quite significantly within that first one to two weeks of treatment if they're on an effective dose of the antiviral if their dose isn't high enough then those symptoms can linger and I get a lot of second opinions of cats that are still on three different types of eye drops and um prisone but they're only on six M perig of um Ram dese which was one of the first published dose rates which we've now revised as soon as you bump those cuts up to the 15 Mig Pig those symptoms resolve and we can discontinue those so I'm not saying that um if you've got a cat with over signs that's really painful with its Uvis that you just stop treating it but I'm saying that if your cat's Uvis is due to its FIP and you're not seeing a significant Improvement in the amount of inflammation you need to consider that maybe that cat isn't on an effective dose or you need to switch any virals or look for another complication of that Uvis so sometimes we might see that that progresses to glaucoma and um you know a lens laxation which is a case I'll sort of discuss in a minute but just just in general we don't want to leave these cats on protracted corticosteroids because the concern is that we may impair their ability to mount an effective immune response to help continue to clear this virus and Achieve long-term remission in terms of the minimum monitoring time points that I'm advocating for with these cats at the very least we want to be doing a weight check every two weeks or ideally weekly if they're being managed at home so sometimes we will have cats that bringing them into the clinic is just too stressful too traumatic or it's too expensive um I think the the fallback is to have um you know diligent owners invest in some baby scales some digital scales at home and be communicating with you what their weight's doing and how they're how they're um progressing but in general I want to be seeing them if we can in practice at least every two weeks over the course of treatment I um have said to focus on the clinical response in the first 12 weeks because sometimes blood results will look a bit worse before they get better with respect to globulins in our aive cats and again I'll speak to that in a minute now that we have Publications advocating for six weeks of treatment in some instances then I'm definitely going to be doing a blood test at four weeks if I have a cat that's responding really well I want to know that everything's normal at four weeks so that I'm treating them for at least two weeks Beyond normalization before I discontinue drug so um you know for those instances I probably would introduce an earlier check sorry clicked ahead um but otherwise um definitely at 6 to 8 weeks and definitely again at 10 to 12 weeks to make sure that things have normalized and they've stayed normal before you discontinue has historically been how we monitored these cats and at a minimum we want to be doing a CBC biochemistry if you have access to acute phase proteins you can absolutely include an AGP and serum amalo a if you've done a dose increase and you need to recheck well you should recheck that cat um within one to two weeks to make sure you've seen an quate response to that dose increase and generally if you do need to sort of do a dose increase or they've not met your emission criteria by the defined date I'm generally extending things into weekly increments with them this is the trend that I've alluded to a couple of times around um weight drop and globulins going higher in our effusive cats so this is this is specifically for effusive cats um it's quite common that around the point of aus resorption which is typically around that two we Mark that we see a spiking globulins a transient drop in PCV and a dip in their weight and um our hypothesis for what's going on here is that these are often very high volume highly proteinous um effusions that are occupying a third space and that we are you know essentially seeing resorption of um those proteins and that fluid back into the circulation which is creating the spiking globulins a bit of hemo dilution that's producing that PC V drop and then um a transient weight drop as they're peeing out that extra fluid but from there things should normalize and weight should start to come up what do we consider to be a suboptimal response um so these are essentially the the Milestones that I need my cats to hit if I'm just going to continue treating them at the the sort of standard dose rate and duration um if we see pyrexia persisting Beyond 5 days I'm going to be tweaking doses if fusions are still hanging around Beyond 2 weeks I'm going to be considering adjusting things um hypog Global anemia for me really I want to see that actually probably normal closer to the six we Mark but with the Munich population of cats both with this new prospective that was published but also their original paper using mustion um their globulins were often normal by the four week Mark so I think there can be some potentially Regional differences or just individual case differences again whether it's a severity issue or whether there's actual differences in how susceptible the virus is in different parts of the world um but in general if I've got a hypog global anemia Beyond six weeks I'm going to be adjusting doses um or any new referable signs to FIP at any stage during treatment so this was one of our um first kitties that was recruited that was on a much lower maintenance dose than we're now advocating for who kept having breakthrough um anterior flare and uiis that would also correlate with the spike in globulins that kept necessitating dosing increases adverse drug reactions with REM Desir and GS there is a potential for alt elevations we sort of seeing like mild alt elevations kind of reported in most of the literature in my prospective cohort it was really hard to elicit whether or not this was like a disease or a drug effect or something unrelated but they're rarely or in my instance they've never required specific treatment they're sort of not usually more than um you know more than one times the sort of reference interval so it's not something that's necessarily requiring specific treatment I don't advocate for any supplements routinely with my FIP treatment um and they all seem to normalize and do well with REM dese um injection site discomfort and Mild skin irritation are definitely reported and that appears to be anecdotally more severe if you're using unlicensed GS as um as subcutaneous injections troubleshooting these cases so um what do we do if we do have a delayed response if they're not meeting that criteria the first thing you need to do is ask yourself this question is it FIP to begin with um I'd say over the last six months I've seen a really big shift in the emails that I'm receiving for case advice it's gone from how do I access these drugs to dvms that are now seeing cats that have ended up on Pat ractic courses of antivirals that didn't have a confirmed diagnosis to begin with and we we're trying to sort of retrospectively decide gosh you know is this FP or have we missed the point and is there another pathology going on so one was it FIP to begin with and even if it was if you achieved a definitive diagnosis and you're able to get biopsies and imunohistochemistry and had all of the referable signs have you checked for another comorbid pathology um because increasingly I'm starting to see these cases where yes they had confirmed FIP but actually they had lymphoma too and we didn't request the the standard hystology we went straight to imunohistochemistry and we missed the fact that actually there's cancer in this animal um or is there a secondary um infection is there a concurrent um bacterial component to what's going on with them it's really important that before we just continue on and and do dose increases with these antivirals if we didn't have a strong strong index of Suspicion as clinicians that these cats had FIP to begin with then I think you really need to question whether you continue that antiviral or stop and start looking for another disease um if you do have a strong index of Suspicion it's making sure we're not missing something else going along parallel with that FIP but if you are confident that you're dealing with FIP and it seems to be lagging behind those Milestones the first thing I do is a dose increase by 10 to me 10 sorry 5 to 10 me per K per day this is definitely when I'd be moving to a divided dose and if you are in an area that's got therapeutic drug monitoring available then that's something that I'd request on the animal but therapeutic drug monitoring is still very much in its infancy and there's not anyone in the US that's routinely offering this at this stage so just put that in a a watch bucket um this is when I would be considering switching to a different Annie viral um such as Eid 1931 m p or Pax and I think we do need to reassess the role of immune modulators and there are some exciting prospectives that are underway at the moment sort of reexamining some of these feel free to reach out to me though I talk to vets all around the world on um cases with FIP so if you're feeling a bit stumped and you're not sure don't be shy I'm very happy to answer questions I'm going to skim through this really quickly mainly because mola p and Eid at the moment are not legally available in the US these are the current recommended dose rates that we using the big difference is that it's always bid and it's always oral with um mola Pur and with Eid um watch this space i' I've put there because Eid may eventually be released by Stokes because boa do it and I know that they sort of initiated conversations around whether Stokes can get eid1 1931 into the us but there's a much narrower safety margin with these drugs um there's a slightly different mechanism of action with these antivirals where they um do do have a potential mutogenic um impact both from a host and a virus perspective um so you want to be wearing gloves uh you need to be careful for adverse side effects and the main one that we see is lucenia so bone marry suppression is something that we document with higher doses um but there's a lot more adverse effects that we're sort of noting in the M Pia literature having said that in some Avenues this is the only legal um option so where m p has been registered for Co use so um particularly over in Asia places like Japan are using a lot more m in Australia we're using a lot more M overall survival rates are coming out around 77% so still a good chance of survival but for me I really want to reserve these drugs to be a second line antiviral mainly because of the safety concerns the um the potential in human literature we've seen the emergence of specific viral mutations in Co that um suggests that the use of mov has created that um genetic drift in those viruses so I think it's really important that we exhaust GS and REM Desir as an option before we move to the second line antivirals in my opinion Eid there's been um a prospective case series similar um adverse effects were noted the doses range from 15 to 20 migp KB in that instance Hax is the drug I want to spend a bit more time on because this is a drug that um dvms in the US can use off label so you can write a prescription for this and most of the the corner drugstores are going to stock this like your your regular human pharmacies will generally be stocking paid paid contains two different antivirals there's neat which is the protease inhibitor which has the antiviral action um and ronov which sorry isn't an an viral it contains two drugs neat is the antiviral ronov is a PK booster um so essentially neat is metabolized really quickly um but it's metabolized via the cyto um for p450 pathway ronov inhibits that so it delays metabolism and keeps plasma concentrations higher for longer um so that's something that UC Davis are doing some really exciting work with and um hopefully we'll have some Publications from them in the next 12 months uh but we have started using this in cuts that have failed GS failed mon the P where we're really um sort of don't have many other options and so we've taken an educated stab in the dark as to a dose rate um and what we've been advocating for is essentially a quarter of the human um dose rate which works out to be half of one of the neat tablets and a quarter of a ratton ofir tablet twice daily um we use this in addition to GS or in addition to mure we do not use paid as a monotherapy um but it's definitely becoming my sort of go-to option for True refractory FP particularly if you're based in the US this seems to be the main um accessible option but it's expensive you're looking at about $1,500 us per box and that box is only going to last 20 days at that dose rate um I know UC Davis are actually trailing a lower rate so using a quarter in aatul and an eighth of the reton ofe um and it it it may work out that that's going to be just as effective so that's sort of something else you could consider but so bringing it all together how do I decide which things I'm going to use if I'm hypothetically now based in the US as a clinician um essentially the first question is going to be how sick is your animal if it's ab tunder and it cannot swallow then absolutely IV is going to be your best route and you need need to scramble to try and find either legal Ram deser or this is you know a reality where unlicensed parental formulations probably do still have um a place at at starting to turn these animals around um I would then transition them to GS 441524 to complete a total of 84 days or if they're responding brilliantly and they tick all of my criteria then maybe I'm considering a shorter duration these days um if they have a competent swellow reflex go with oral from the get-go I don't care what form of FIP they have if you have a suboptimal response consider adding in off label Pax leid or owners May Source unlicensed M or eid1 1931 and if you have reemergent FIP then um you can consider repeating GS at a higher dose rate or this is definitely when I would be adding in pxs ofid or again um there might be unlicensed avenues for Mur eid1 1931 uh again just to note to the dvms in the audience don't just always think that an antiviral is the only thing these animals need usually for the first few days they're going to benefit from other supportive medications particularly um sort of moratin or andanet tronin and sort of metazine to kind of help from a nutritional standpoint monitor their blood pressure some of these guys are pretty hypotensive in the first um week of treatment so just be um monitoring these animals as you would for any other sick cat it it needs support now I'm just going to work through one case because I think we're we're going to run out of time unfortunately this is um an email case um that was that I've been sort of assisting with who is based in Australia but this is a seven-year-old male needed domestic short hair that presented with Lethy pexia in appetence a large volume ofes and a palpable abdominal Mass with no Opthalmic or neurologic abnormalities there was a istent hyp globular anemia on um biochemistry and an Alum ratio um in the blood of 0.5 they did fluid analysis and it was pretty high protein it's 50 g per liter and the AL glob ratio is 0.5 it was technically classified as an exate because there were quite a few cells there um but that's not uncommon for FIP and it's sort of on my list of things to to put some data around and publish is not all of these cats um are just a pure um sort of low cellular high protein yellow straw sticky fluid we do get some that have um lymphatic fluid or or Hemorrhage or more exudative um presentations um and the pathologist on the cytology report noted that FIP infection is suspicious and considering the history provided and recommended uh doing a coronavirus PCR which was performed but was negative now um again I'm not diving into Diagnostics today but unfortunately a lot of our confirmatory tests do have the potential for false negatives so we end up in these tricky situations where it's like we can't quite catch the virus in action but this cat is meeting a lot of my criteria for a really high index of Suspicion of FIP um these vets did do um sort of aspirates of the mass which um looked P granulomatous um there weren't any um obvious bacteria on Gram stain they didn't specifically culture the fluid but um C logically they didn't see any evidence of of infection and there was no suspicious cells to suggest neoplasia so FIP was really at the top of our differential list for this cat and the owners were not comfortable taking this cat to surgery um they they were really not keen to go for invasive Diagnostics um I'm going to skip through what your differentials are just because I'm running out of time unfortunately but to just continue this story through essentially um we elected to do a treatment trial with this cat because for an effusive FIP with non Opthalmic and non-urologic involvement 15 migp Sid of GS should produce a pretty considerable response in the first week to two weeks of treatment but unfortunately although at two weeks later Fred was much happier and weight was stable and there was no further fever there was a persistent large volume of fusion and and the abdominal Mass was still there and again I'm not going to jump to the quizzes but in terms of what you do there um you know we're we're constantly torn about okay well this is a cat that's not meeting that criteria is this definitely FIP and there was another discussion around taking this cat to surgery for biopsies versus do we go with a dose increase in the Gs and the owner elected to go for a dose increase in the Gs so we bump this cat up to 15 m per per day four weeks later cat's still happy still eating pretty consistently weight still stable still no fever but still has a large volume a fusion and an abdominal mass now at that point um we proceeded with exploratory laparotomy so the vets that were managing this case were able to discuss that we really need to go back and reassess what's going on there was a mass associated with the J junim and biopsies were taken and the histopathology report has confirm that this was actually a case of feline sclerosing is anilic fibroplasia now I've not seen one of these lesions produce a large volume um abdominal affusion but um this is just going back to the fact that cats don't read textbooks and they don't like to fit into boxes um medically so um this cat essentially received six weeks of GS for a nonviral disease and needed to be started on corticosteroids and we've essentially inadvertently deprived this cat of a rapid Improvement in its Disease by six weeks because we hung our hat on FIP and I I still don't know whether we could do anything differently in this instance but more and more my inbox is flooded with these kinds of cases where we weren't able to confirm a diagnosis and sometimes the index of Suspicion of FIP is way lower it could be something as simple as a non-regenerative anemia ends up on a 12-week course of unlicensed GS because an owner well- meaningly founded as a differential and connected with a well-meaning social Media Group and the bid in between has been skipped and this is again where it's so important if you're not a DVM and you're in this space of of FIP please be directing potential cases to their clinicians to be sure that we're ruling out other pathologies because um things just aren't as clear-cut as they seem and although our general sort of conversation has been well look we're really happy with the safety profile of GS let's just start it because we don't want these cuts to get worse and we know that the longer we delay treatment um the the poorer the prognos in some instances but if we're not really really really suspicious of FIP I implore you to hold off on commencing antivirals until we've done some further Diagnostics because now we're ending up in this really muddy situation where we we can't we can't now distinguish whether or not these are true resistant infections or whether this was never FIP to begin with because what we do know is that once we start these anti viral any test for FIP is probably going to be negative within a week of starting treatment so we can't really go backwards without stopping it and seeing whether they get worse so um really do your absolute best to try and be as confident as possible about a diagnosis and even if you can't confirm the FIP be confident you've tried to rule out all the other things that could be going on um there was one final case but it was a neurologic f FIP that's been managed over in the US and I'm just going to run you through um more the video progression essentially this cat was given a presumptive diagnosis of um neurologic FIP and was started on unlicensed um formulations of GS and improved a little bit initially but then started to deteriorate again when they were switched to oral unlicensed formulations this poor little kitty became increasingly a taxic um was really struggling and could sort of barely move around um at the point that the DVM reached out to me for case advice and I don't know whether this is going to let me advance my slide because I made my videos too big um ultimately we added in PID in this cat and this cat um responded um started to improve within six days of starting treatment um two weeks into starting treatment um it was able to jump up onto its scratching post again and I've connected with these owners and this little kitties um you know now a month or so into treatment this is his little mate but you can see we've got function again this cat's way less axic he's um you know playful and and sort of moving around um a lot more freely um there was a complication with the I uiis had um created glaucoma and a lens laxation and then they've needed to enucleate but this cat's now happy and and improving I'm going to leave it there treatment's going to continue to evolve rapidly um so just make sure you're continually checking in with things and um these are some webinars that you can watch back on demand that myself and some other esteemed colleagues in this area have produced in um four Stokes for sort of uh DVM advice so if you want to touch up on diagnostics um if you want to hear more in-depth discussions on things you can definitely access those on demand and if you're a DVM that loves infectious disease um come to isad in Vancouver in October I'm going to be speaking there um and I will stop sharing my screen and wind up well thank you so much Sally that was amazing and just so useful we really appreciate this really um comprehensive review We and of course this is an evolving story like the virus is evolving uh we have time for one or two questions um I'm GNA ask one from somebody that was submitted beforehand they asked questions about they had a a cat that was treated um he's a two-year Survivor after receiving uh injections from online GF injections uh and notic that the cat developed apparent p p appears eating and is asking whether you've noticed that as a side effect of no um that's the first time Pik has been raised I I've definitely not heard on it and I guess my my gut reaction to that would probably be it's unrelated okay fair enough um here's a question that talks about whether KNE crops have been done to track What treatments du to the virus within the tissues of the body yeah and you know that's kind of that's what we're all itching for but the the happy problem that we're having in the prospective study space is that not many of these cats are dying unfortunately the three that did die um in my perspective because we always need to work in accordance with owner um preferences around this and also we were dealing with the logistics of the middle of Co lockdowns and um there were sort of two instances where we just couldn't get careers and labs to coordinate in a timely manner to achieve a necropsy um or owners have declined necropsy um I know UC Davis have um you know done necropsies in any cats that haven't um survived in some of their studies just talking to Crystal rean there and they're having a really hard time pulling trying to find virus anywhere these cats tissues after being on antivirals for usually a week we did have a really interesting um case that was reported out of Germany so um the same group at Munich who did the mustion study back in 2021 using um mission to treat FIP one of those survivors who was doing really well sort of six months down the road very tragically got hit by a car and the owners very vigilantly realized the opportunity from a scientific perspective and presented the cat immediately to the uni for necropsy and they were unable to find virus anywhere in its cats tissues so the suspicion is that we are probably dampening down viral replication to a point where the immune system can figure out how to now mount a competent response to hopefully clear these cats because I'm definitely not seeing an inundation of reemergent FIP years down the road there's a handful of cases I'm aware of that um you know meet that criteria but I suspect um you know these cats may actually have a more robust immunity to Corona viruses um on the flip side but we need data around that fair enough thank you uh and if anyone in this audience is the owner of one of these beloved survivors and their cat does succumb to a different disease although this is a horrible thing to have to think about as pet owners we never want to be thinking about this but these are really important cats for us to understand and I think doing necropsies um is going to be really important and I know there's a lot of institutions in the US that would be interested in this so if that eventuates I would really encourage you to allow your DVM to do an necropsy well thank you that's certainly very important uh this question was probably prompted by the covid uh situation is there any correlation between canc diagnosis of FIP and blood type that you're aware of not that I'm aware of um that's an interesting question I think um we really need to dive into the Immunology um with these cats more and there's some people working in this space already and so I think blood type should be one of the many things that we're looking at but I'm not aware of a susceptibility thing with blood type emerging in the FIP literature today okay um and uh one one final question uh what What's believed to be the mechanism of imh a in cat is this in cat is it antigen deposition or do we have any idea or do we know no know I don't know that we we really know I guess um you know cats are quite good at getting secondary IM to any kind of inflammatory process or other disease process so I'm I'm personally kind of lumping it in the same bag as you know a secondary imha for other disease reasons um I know a Petra is cating some cases of imha um hopefully she'll sort of be looking at publishing that once she gets enough cases together whether we can tease out some commonality in terms of what's triggering it and I think again as um viral sequencing becomes a bigger conversation in this space we may start to tease out that particular mutations might lend themselves to slightly different manifestations of FIP but at this stage we don't really know okay thank you and one final question this is sort of a combination question uh the risk about exposing cats with FIP to other cats especially young kittens will they still be shedding Corona virus and other infecting other cats potentially and I I'll add on to that has do we know has there been any evidence of a cat shedding mutated form of virus or is it still an internal mutation hypothesis um I I think we we are going back to the drawing board I'm pretty much everything we thought we knew about this disease now that we have survivors that we can study and you know these are RNA viruses that love to mutate I think it was naive to think that things would ever stay the same um in general historically it seems very rare that cats um who are exhibiting fipv um so actual FIP um presentations are actively shedding infective virus however um the main thing that's really thrown um that into question more recently is a a huge outbreak of FIP that we've seen in Cyprus and there's a big um International collaboration underway to flesh out um the the real um the the issues of how that emerged and um Cornell are doing a lot of the sequencing for this it does look like in this instance we've had a recombination with a highly virulent canine Corona virus that has potentially led to a directly transmissible form of FIP and we definitely have these um you know documentations in the literature of outbreak kind of situations that seem more than just um standard kind of we do think there's a genetic susceptibility that needs to be fleshed out so sometimes lates will go on to all develop FIP but they've been rehomed to completely different environments we're still figuring it out but in general it seems unlikely that an FIP cat is going to directly transmit to um another animal in the house and I'm not actively recommending that you quarantine these cats um at the moment if you're not in Cyprus or or Europe but um if you feel like you are seeing an outbreak of FIP and there is a suspicion of transmission reach out to to Cornell um Gary Whit there I'm sure we'd be doing some sequencing because we do need surveillance to know whether or not we're seeing new strains of FIP emerge and are we seeing Cypress strains hit um the us or Australia um so it's it's another evolving be but in general no most of the time thank you and of course evolving situation yeah well um yeah first I want to thank you so much from the bottom of all of our hearts for doing this this is really wonderful um and thanks for staying a little extra time of course uh I think that's about all the questions we can get to today I believe uh as you said the slide deck will be made available yes and I've um I've sent through the PDF I remove the case examples just to kind of streamline Le a little bit more but yeah people um are welcome to refer to that as I said there are some good um watch On Demand um webinars around how all the literature came to be and what the diagnosis um how to sort of nail down a diagnosis um that is all parked on that Epicure Stokes um web page as well okay that is so great and we'll be sharing the PDF with attendees so thank you so much and so in closing again we really can't thank you enough for doing this has been wonderful uh to uh folks from all around the world who are joining us thank you so much for joining us I know please keep track of Dr Collins kagin's uh work um and use those other resources that she put up if you have questions contact us if we can't answer them we'll contact her because she's thank you so much um and again remember everybody and here's my plug the Cornell feline Health Center we can only do this uh with the support of donors we're completely donor supported so please consider following us on Facebook and on Twitter or X whatever it's called nowadays uh join us as a member um and thank you so much everybody uh for joining us today uh uh without any further Ado I was going to say good night but I will say good morning to you Sally and I hope you wonderful the future yes but you know best regards uh to all of you from all of us here at the center and I hope you're all doing well and please keep your eye out for future webinars Take Care thank you