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Clinical Review

Treatment of FIP in cats with remdesivir
David Hughes BSc BVSc
(Merit) graduated from
Sydney University in 2010.
He immediately landed
a new graduate job in apractice he had been working as a trainee and went
on to purchase this practicein 2013 - Concord Veterinary
Hospital. The hospital andvets in the practice havelong, strong association with The Cat Protection
Society of New South Wales, something Hughes isproud to continue. This gives him a high feline caseload and a strong interest in all things feline medicine.
As a result of this case load and experience withcats and kittens – with the assistance of Jacqui
Norris and Richard Malik – Hughes has developed a
special interest in the clinical side of treating
patients with FIP. David also has a special interest in
ophthalmology which holds him in good stead forocular and CNS FIP cases. His greatest joy has comefrom seeing essentially end stage cases of FIP leave
Concord Veterinary Hospital entering remission andon the way to a clinical cure.
Gretta Howard BVSc, MVS,MANZCVS (SAM) graduatedfrom the University ofSydney in 1999. She worked
in mixed practice in country
NSW, then in private
practice in Sydney whilst
completing a Masters
through Murdoch University.
Howard worked as a locum
in numerous practices
throughout the UK, and on the way homevolunteered in Sikkim, India with Vets Beyond
Borders. In 2006, she gained Membership of the
ANZCVS in Small Animal Medicine. Howard has akeen interest in infectious diseases. During the past
year during lockdown, she started volunteering
as a vet with the FIP Warriors Facebook group,
communicating with other vets and owners aroundthe world, to assist in the management of their
FIP cases. Through this rewarding experienceshe has learnt many tips and tricks from other vetsand rescue groups who treat vast numbersof FIP cases. Howard thoroughly enjoys clinicalwork at Turramurra Vet Hospital in a family
practice in Sydney’s North Shore.
Richard Malik DVSc
MVetClinStud PhD FASM
graduated from the
University of Sydney in
1981. He is a specialist
in small animal internal
medicine and has a special
interest in infectious
diseases of dogs and cats.
Although active in clinicalresearch through postgraduate scholars, he issemi-retired, living in the southern Highlands of
NSW on a brumby sanctuary. He helps out at a few
practices including Southern Tablelands Veterinary
Hospital, Double Bay Vet Clinic and Paddington
Cat Hospital. He also works for the Centre for
Veterinary Education helping to organise CPD.

www.theveterinarian.com.au

Feline infectious peritonitis (FIP) is aninfectious disease of cats, predominantly
young cats. It occurs when feline entericcoronavirus multiplying in the intestines
undergoes a critical mutation whichchanges its tissue tropism from enterocytes
to macrophages. FIP virus moves roundthe body in macrophages – the ultimate
Trojan horse mechanism. This leads to adisseminated infection and the development of a fibrinoid necrotising vasculitis
and serositis due to deposition of immune
complexes consisting of cat antibodies and
FIP viral antigens.
Broadly speaking there are two forms of
FIP – effusive (‘wet’) FIP and non-effusive(‘dry’) FIP. The actual disease process canoccur in the abdominal cavity, the thoracic
cavity, pericardium, the eyes, or the central
nervous system. Mix and match combinations of different tissue involvement anddry and wet disease are not unusual.
Until recently, a diagnosis of feline
infectious peritonitis (FIP) was by andlarge a death sentence for a feline
patient. But that notion has been
turned on its head over the last few
years as a result of the pioneering
work of Professor Niels C. Pedersen
and colleagues at UC Davis.

Omega-interferon(Virbagen)andpolyprenyl immunostimulant (PPI) were
the first drugs used to treat FIP and both
had reasonable efficacy in some patients.
Omega interferon was useful in cases of
effusive (‘wet’) FIP, often combined withlow dose prednisolone according to
Ishida’s protocol, whereas PPI, which waspioneered by Prof Al Legendre, was more
useful in cases of non-effusive (‘dry’) FIP.
In some cases, both drugs were used inconcert. The trouble was that both formsof therapy were often expensive especiallywhen both dugs were used, so althoughpatients might improve and have durable
clinical remissions while receiving
treatment, permanent clinical cures
were exceedingly rare. As a result, mostvets still considered a diagnosis of FIP to
be a prelude to euthanasia.
That all changed a few years ago becauseof the culmination of a life-time of FIP
research by Pedersen. Niels is an amazing
veterinarian, a North American, with
Danish heritage. He grew up on a chicken
farm and initially wanted to be a large animal clinician, but with amazing foresight,
decided a background in basic sciencewould hold him in good stead in the longterm. So, soon after graduation, he
travelled to Canberra in the 1960s to theJohn Curtin School of Medical Research at
ANU where he undertook an immunology
PhD on kidney transplant rejection withProfessor Bede Morris, using sheep as theexperimental model to study lymphocyte
kinetics.
When Niels returned to UC Davis as clinical faculty, he developed a special focus
on infection and immunity. Although hecontributed to a huge range of topics incanine and feline internal medicine, FIP
was his favourite disease because of its
commonness and also its complexity. Hisstudies extended from the 1980s, when thefocus was initially on diagnosis, virology,
and disease pathogenesis, to the presentday, with an increasing focus on therapy.
Working with colleagues at Kansas State
University, Niels showed that a purpose-designed protease inhibitor GC-376 could
prevent and cure experimental FIP in
research cats.1,2 However, clinical trials in
actual feline patients with naturally-occurring disease in the field were somewhat
disappointing for reasons that are notentirely clear. So not easily defeated,
he moved onto a different drug known as
GS-441524,3,4 a nucleoside analogue being
developed by the North American Pharma
Gilead. This drug molecule proved to
be much more effective than GC-376
for treating FIP, both in experimental
infections and in spontaneous cases in
the field. Starting with pharmacokinetic
studies, and then dose escalation studies
using a wide range of clinical cases, Niels
and colleagues determined that the dose
required depended on whether or notthere was ocular or central nervous system(CNS) involvement.5
Surprisingly, Gilead, the pharmaceuticalcompany which developed GS-441524, has
so far shown no interest in developing thismolecule as a veterinary treatment for FIP.
So, to fill in the void for effective FIP
therapy worldwide, various laboratories
in China and eastern Europe started
manufacturing GS-441524 and selling it on
the black-market.

Figure 1: One of many brands of
GS-441524 products available on
the black market

The widespread availability of GS-441524,
often of high quality, and typically very
expensive, provided a way for dedicatedcat owners to save cats with wet or dry FIP.
Studies by Samantha Evans a clinicalpathologist at Ohio State University
suggested a cure rate of possible 80 per
cent in the field. Procuring the drug
is complicated and fraught with issues,
which were circumvented at some levelby help from the Facebook collective ‘FIP
Warriors’. Unfortunately for Australian
cat lovers, the APVMA and Vet Boards
eventually twigged to what was happening,
and Border Force made it much moredifficult to source GS-441524 and safely
import it for veterinary use. Indeed,punitive warnings by the regulatory bodies
were directed at veterinarians who
facilitated the treatment of cats with
FIP using GS-441524.
Ironically, the COVID 19 pandemic
provided a novel solution to this problem.
Gilead had developed remdesivir(GS-5734) as a drug for treating hepatitis
C, Ebola, and human Coronavirus disease.
Remdesivir is a prodrug of GS-441524,
containing an extra chemical side chain(including a phosphate group) that is supposed to improve intracellular penetration(Figure 2B). Remdesivir (as the productVeklury) was given provisional registration(for a period of two years) by the TGA in
July 2020 for treatment of SARS-CoV-2
infections in human COVID-19 patients.
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This process of registration would normally havetaken several years, but the severity of the
COVID pandemic expedited the process byenabling reliance on preliminary clinical trial
data. As remdesivir became a licensed human
drug, it could be readily used off-label inveterinary applications, such as treatment of
FIP in cats and kittens. This has circumvented
problems with using GS-441524 - an unlicensed
drug purchased on the black market, with theallied issues of unproven efficacy, unknown purity, and consistency of product over time. Having
said this, many people believe GS-441524 may
actually be the superior drug, having several
advantages including the ability to dose orally
rather than parenterally.
BOVA Australia, an animal compounding
pharmacy, has managed to secure reliablesupplies of remdesivir to formulate and fill into
vials suitable for treating cats. Studies inAustralia have determined the shelf-life afterreconstitution to be in excess of 7 days andconfirmed efficacy in vitro against Coronaviruses
using tissue culture. Drug analytic purity is
now regularly checked by HPLC. For the past
5 months, Australian veterinarians in every state
have been using it for the treatment of clinicalcases of FIP. Some of these cases have been new
diagnoses, while others were cats that had
already improved using black-market-sourced
GS-441524 that had subsequently become unobtainable. There has been a mixture of effusive
and non-effusive cases, including some catswith ocular involvement (uveitis) and otherswith multifocal CNS disease. Based on approximately 100 cats treated between October 2020
and April 2021, remdesivir is proving to behighly effective at managing FIP infections.
It is slightly easier to administer subcutaneously
and seems a little less painful during injection
than its active metabolite (GS-441524) withwhich it appears to be roughly equipotent.
The molecular weight of remdesivir is
603 g/mol, while the molecular weight of
GS-441524 is 291 g/mol. At first glance, thismight suggest that cats being treated withremdesivir require twice the dose of cats receiving GS-441524, but this does not account for the
improved intracellular penetration of remdesivir
compared to GS-441524. The suggested dose
rate for remdesivir in human patients with
COVID19 is a 200 mg loading dose intravenously(IV), followed by 100 mg IV daily. For a 70 kg
human patient, this represents a daily dose of
1.3 mg/kg, so considering normal allometricscaling a dose of 5-10 mg/kg daily for a catsounds in the right ballpark.

Currently, Australia is the only country where
remdesivir is readily available via prescription
for veterinary use via BOVA Australia. However,veterinarians in India, South Africa, and someparts of Europe, have also started accessing the
drug using human suppliers.

lymph nodes (Figure 5) or marked thickening of
the iliocaecocolic region (so called ‘focal FIP’)(Figure 7).

Figure 4: Abundant highly echogenic fluid(fibrin strands) in a cat with high protein
ascites due to effusive FIP
Figure 3: Severine Tasker’s amazingly
comprehensive and practical reviewof the diagnosis of FIP

Diagnosis
The full differential diagnosis of FIP is beyond
the scope of this article, but readers are strongly
encouraged to read the superb article byProfessor Séverine Tasker in the Journal of Feline
Medicine & Surgery.6
Although FIP can occur in cats of any age,most cases occur in kittens and cats younger
than 3 years-of-age. Persistent and often highfever that fails to respond to antibiotic therapy(and often NSAIDs) is a common finding, as iselevated total plasma protein due to increased
globulin concentrations (diffuse gammopathy
on serum electrophoresis). In effusive or ‘wet’
FIP, the albumin to globulin ratio may drop toless than 0.45. Acute phase reactants such asserum amyloid A and á1-acid glycoprotein tend
to be markedly elevated. Many cats with FIP also
have secondary immune-mediated haemolytic
anaemia, ‘transaminitis’ (increased AST and
ALT) and icterus.
Diagnostic imaging is critical to a timely
diagnosis, and this has been greatly facilitated byadoption of digital radiology and the widespread
availability of diagnostic ultrasound in companion animal practice. Pleural effusion is readily
appreciated from chest X-rays, while abdominal
effusion is best detected using ultrasound(Figure 4), especially if you have a range of highfrequency transducers. Note that in some cases
the fluid pockets can be focal and loculated – sohave a careful look around the abdomen!

If you see an effusion – tap it – as fluid is the best
diagnostic sample. If you can see a granuloma inan organ, or if large lymph nodes are evident –do an FNA, make a smear, stain with RapidDiff
and look for pyogranulomatous inflammationin the absence of visible infectious agents(Figure 6).

Figure 5: Marked mesenteric lymphadenomegaly in a cat with dry FIP

Effusive disease is obviously much easier todiagnose as ascitic, pericardial or pleural fluid
provides a convenient sample which can be
examined cytologically and via fluid analysis andthen subjected to immunofluorescence (IFA) for
FIP antigen or reverse transcriptase PCR todetect FIP nucleic acid. IFA is performed at
VPDS, B14, University of Sydney (easily arranged
through Vetnostics, QML, ASAP, VetPath,
Gribbles or IDEXX). Dry FIP is more problematic, as usually it requires a fine needle aspirate
biopsy of pyogranulomatous lesions in theliver, kidney, or abdominal lymph nodes.
Occasionally, wet FIP cases can paradoxicallyhave fluid specimens which are negative on IFA
and/or PCR testing, yet the patient still likely has
FIP as reflected by a favourable response toremdesivir therapy.

B
A
Figure 2. (A) BOVA Remdesivir reconstituted and ready for therapy. Once it is reconstituted, thecontent of a vial is stable for at least 7 days at 5 oC – and usually a vial is used up in 3-7 days.
The vial should be stored refrigerated (both before and after reconstitution). (B) The pathway
by which Remdesivir travels intracellularly to be activated as GS-441524

Remdesivir is provided by BOVA as a 100 mg vialwhich is reconstituted with 9 mL of sterile water
for injection to give a 10 mg/mL solution(10 mL per vial after reconstitution). It is important to use water for injection and not sterile
saline to avoid making the solution excessively
hypertonic.
www.theveterinarian.com.au

Often there is some fluid around the kidney
underneath the renal capsule, kittens can havescrotal oedema, while in the odd case the effusion is limited to the pericardial sac. But the key
thing is – look for (i) effusion in any body cavity,(ii) granulomas in the kidney, liver, or lungs,(iii) large intra-abdominal and mesentericFigure 6: RapidDiff-stained smear of a fineneedle aspirate from the mesenteric lymph
nodes of a 4-year-old Oriental cat with dry
FIP. The prominent macrophages are the key
to the cytological diagnosis. Photo suppliedby Patricia Martin

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Treatment
We have been treating cats with FIP using remdesivir since October 2020, and our protocols areconstantly evolving with experience. We try to
avoid being too prescriptive in our recommendations, as our suspicion is that there is not asingle protocol which suits all patients, and every
case has unique considerations, including thesize of the patient, whether the cat is still ‘happy’and eating adequately, or is depressed and dehydrated. A key consideration is the emotionaland financial commitment of the owner. A key
feature to mention is that the drug seems very
safe, even in sick cats and kittens.
Remdesivir is expensive, and the owner needs
to make a commitment to a costly treatment
course that spans a period of 3 months. For
most clients, this represents an emotional andfinancial strain, and so cheaper options may
work better for certain clients and in certain
circumstances. Our view is that in many cases
money is better spent on the antiviral therapy
rather than on extensive monitoring.

Figure 7: Marked thickening of the iliocaecocolic
region of a cat with so called ‘focal FIP’, usuallya form of non-effusive FIP. Photo supplied by
Penny Tisdall

One approach in newly diagnosed cats withsevere disease, is to hospitalise cats for the first3 - 4 days of therapy while remdesivir is given
intravenously (IV), effectively as a loading dose.
Patients begin their treatment with remdesivir
while they are receiving IV fluid therapy (use
2-4 mL/kg/hr; Hartmann’s solution or
Plasmalyte on the first day, and subsequently
0.45% NaCl and 2.5% dextrose containing
20 mmol KCl/L).
On day 1 of hospitalisation, remdesivir isadministered at a high dose intravenously(10 mg/kg diluted to 10 mL with saline andgiven SLOWLY over 20-30 minutes or longer
manually or using a syringe driver; in humanpatients it is given over 2 hours) to provide aloading dose to fill up the volume of distribution
for the drug. This achieves rapid antiviral efficacy.
Note that many cats can appear somewhat
depressed for a few hours after the IV infusionof remdesivir, especially if it is given quickly.
In human patients, remdesivir may cause infusion-related reactions, including low blood pressure, nausea, vomiting, sweating, or shivering.
The benefit of starting therapy intravenouslyis that dehydration, if present, is corrected,
you have IV access in case you need to administer
other drugs (such as anticonvulsants). Importantly, once the IV catheter is secure, daily
injections of remdesivir do not cause any pain
or discomfort.
Cats with FIP treated with remdesivir typically
improve markedly over the first 2-3 days during
preliminary IV therapy. We have observed,
however, that effusive cases and especially thosethat have presented with pleural effusion prior
to treatment should be monitored closely, as
the combination of the antiviral effect of
the remdesivir and greater than maintenancedelivery of crystalloids can result in transient
worsening of pleural effusion. This necessitatesdrainage twice daily using a 19-gauge butterfly
needle and a 3-way stop-cock (ideally using
ultrasound guidance to find the best window
for needle insertion). These ‘secondary’ pleural00

TheVeterinarian APRIL 2021

effusions can be fatal if not detected early andseem to occur in about 1 in 10 effusive cases
treated with remdesivir. A further problem
occasionally seen at this time is the developmentof neurological signs, including seizures. Ourview is that this is not a drug effect per se, butrather the unmasking of subclinical CNS FIP.
Such cats need careful observation, while
the development of seizures mandates the useof anticonvulsant medication, such as midazolam (0.3 mg/kg IV) or alfaxan or propofol
IV to effect, followed by levetiracetam(Keppra) (10–20 mg/kg, PO every 8 hours).
Phenobarbitone is a reliable anticonvulsant,however it has the propensity to increase themetabolism of many drugs, and until we better
understand the pharmacokinetics and metabolism of remdesivir, it is probably safer to use
levetiracetam in this setting. Some cliniciansalso administer dexamethasone or prednisolone
as a one-off treatment to help settle down the
CNS inflammation.
Although we generally advocate preliminary
IV therapy, FIP patients that are still ‘happy’and still eating well do not require high dose IV
therapy at the outset and can instead be started
with subcutaneous injections at 5-10 mg/kg/day,with the dose depending on whether they do or
do not have ocular or CNS disease. This, ofcourse, is far less expensive as the cats or kittens
do not need to be placed on an infusion pumpand kept in hospital; so, for clients who havefinancial constraints, this might be preferable
way to begin therapy. One should be flexible,
because necessity is the mother of invention.
Some clever colleagues, like Jim Euclid, havedeveloped a hybrid approach where kittens
receive subcutaneous fluids as a bolus daily andremdesivir is injected into the fluid ‘lump’.
Subsequently, cats are given ONGOING
subcutaneous injections of remdesivir, usually ata lower dose. For routine FIP cases – we generally
have used 5-6 mg/kg once daily (SID) as remdesivir is thought to be roughly equipotent toGS-441524 in vivo (Niels Pedersen, personalcommunication). If there is prominent ocular
involvement, we recommend 8 mg/kg SID bysubcutaneous injection (SCI) and cats with neurological FIP with CNS signs are given 10 mg/kg
SID SCI.5 As well, cats with severe uveitis should
be given topical corticosteroids (Pred Forte or
Maxidex) for 2-3 days (no longer!) and atropine

Figure 8. Focal dry FIP, with pyogranulomatous
inflammation of intraabdominal lymph nodes.
Rather than undertaking an exploratory
laparotomy, lymph node biopsy, histology andimmunohistology, it might be more cost effective, where there is a high suspicion of FIP, totrial 3 days of IV remdesivir therapy. A FNA ofthe enlarged lymph node is probably the ideal
diagnostic option for practitioners with thisskillset. This is the same cat as in Figure 5,
owned by Rose Jackson, a veterinary nurse

eye ointment. In a few atypical patients, interestingly, both Ragdoll cats, it was necessary toincrease the dose of remdesivir to 15 mg/kg
once a day to have the desired effect.
It is important that owners are counselledproperly on how to optimally administer daily
injections. Cats will find the injection less painful
if the remdesivir solution in the syringe isallowed to come to room temperature rather
than be injected when cold from the fridge.
Furthermore, teaching them simple tasks suchas using a new needle when injecting the cat(i.e., use a different needle to the one used towithdraw the drug from the vial) and using 22 or
23-gauge needles, will make injections much
more tolerable. Alternately, veterinarians might
prepare a full weeks’ worth of injections for theowner, to make things simple and sterile, in a
box to be kept in the fridge, with a new syringe
to be used every day.
In cats that continue to find the SC injections
painful, we have used gabapentin orally (50 to
100 mg) and/or transmucosal or SC buprenorphine administered 30-60 min prior to theinjection for sedation/analgesia. The area to be
injected can also be clipped so that topical
EMLA cream can be applied 30 minutes prior
to injection. In exceptional cases, we have placed
a new cephalic catheter every 4-5 days toallow owners to give IV therapy rather thanSC injections.
In situations when owners cannot afford a fullcourse of therapy, or where injections are
deemed to be too painful, we have used mefloquine (Larium; 62.5 mg (1/4 tablet in a gelatine
capsule) with food 2-3 times a week for an average sized cat; obtained from a specialised compounder or a local pharmacy) after preliminary
remdesivir therapy. Mefloquine has been shownto have an antiviral effect by Phillip McDonagh,
Jacqui Norris, Merran Govendir and theircolleagues at the Sydney School of Veterinary
Science.7 This probably occurs by mefloquine
usurping biochemical intracellular pathways
utilised by FIP virus, a mechanism that has
recently been shown also for the anti-leprosy
drug clofazimine,8 and several other drugs in
the pipeline.
The main advantage of remdesivir therapy for
FIP is that the product we are using is subjected
to quality assurance. It is only a matter ofwriting a prescription with the client’s name andaddress, the name of the patient and the doseto be administered, and BOVA can usuallycompound and provide vials to any veterinarianin Australia within 24-48 hours.
Currently, the cost of a 100 mg vial is $250 plus
GST and postage ($280 typically at the practice),
although it is possible that in time the cost
will come down because of economies of scale.
Of course, buying multiple vials at one time
reduces postage and handling fees. We believe
most owners will feel much more comfortableobtaining a product from a well-known
Australian company, rather than sending money
overseas and hoping that black-market drugs of
unknown quantity will make it to Australia safely
without being seized by customs.
Veterinarians wishing to explore this option,or with general questions about FIP casemanagement, can e-mail Drs Richard Malik(richard.malik@sydney.edu.au), David Hughes(concordvets@concordvets.com.au),
GrettaHoward (drgretta@gmail.com), Professor Jacqui
Norris (jacqui.norris@sydney.edu.au), or Dr
Sally Coggins (dr.sallyc@gmail.com) for advice
in relation to diagnosis or therapy. Many
Australian veterinarians with an interest in FIP
have developed considerable expertise in the
management of these cases. For example,
Andrew Spanner in Adelaide has treated inexcess of 10 cases with excellent results. Feline
clinicians, cat only practices and many internal
medicine specialists have managed cases withboth GS-441524 (historically) and more recently,■ www.theveterinarian.com.au

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Clinical Review
remdesivir, and so for vets who are hesitant intreating their own cases, they have the optionof referral.
Clinicians that have accepted FIP case referrals
from general practitioners include but are notlimited to: QLD Rhett Marshall, Marcus Gunew,
Alison Jukes, Rachel Korman; NSW Katherine
Briscoe, Michael Linton, Randolph Baral,
Melissa Catt; VIC - Carolyn O’Brien, Keshuan
Chow, Amy Lingard; WA-Martine Van Boeijen
and Murdoch University Veterinary Teaching
Hospital; TAS Moira van Dorsselaer. All theseclinicians (and likely more we are not aware of)are happy to accept cases for diagnostic work- up
and therapy.

add to the cost of therapy. A compromise is tocollect a few drops of blood to monitor PCV,
total plasma protein (TPP) using refractometry
and the colour of plasma – in that way one
can determine is anaemia is improving, icterus
is resolving and whether the reduction on
gamma globulin concentrations is resulting
in a lower TPP.
Do not be concerned by transient increases in
globulin concentrations during early therapy;
when high protein effusions are absorbed, lots ofextra immunoglobins are dumped into thepatient’s plasma. This can be common even up
to week 8 of treatment but resolves by week 12.
Remdesivir has the potential to cause kidney andhistology or PCR in every patient, while others
are keen to ‘treat for the treatable’ with a 3–5-daytrial of remdesivir, and then proceed to ex lap
if there is no unambiguous response to therapy.

Figure 10: MRI scan from a cat with CNS FIP.
Note ependymitis and ventricular dilatation,
especially around the 4th ventricle (whitearrows)Figure 9: Bengal kitten with CNS and ocular FIP (A: before) and (B: after) after Remdesivir.
This cat also had pulmonary granulomas. This patient was treated by David Hughes at Concord
Veterinary Hospital

Sally Coggins, working with Lara Boland,
Associate Professor Mary Thompson andProfessor Jacqui Norris at Sydney School of
Veterinary Science will be interested in treatingcases with comprehensive diagnosis and monitoring provided gratis. This will form part of
Sally’s PhD program, so you will be helping her
progress her studies by referring cases. As aresult of these studies, hopefully we will develop
have a better idea of how quickly the cats
respond and exactly when therapy can be safely
discontinued. Owners will still need to purchaseremdesivir for therapy. This group also has aninterest in treating cases with interferon-omega
and mefloquine.
But there is no reason what-so-ever why awellmotivated veterinarian should not beable to manage these cases in their own
practice. This is often more convenient to
the owner, especially if they struggle withthe daily injections and need a practice thatis close and convenient.

Most FIP cases do very well with GS- 441524 orremdesivir therapy. Niels Pedersen has written
a wonderfully comprehensive treatment
document which he published on the Veterinary
Information Network (VIN). It’s well worth aread – make sure you have a cup of coffee tokeep you focussed! The article is pure gold.
Some recommendations are provided on how tomonitor cats during therapy. One of us (Malik)
is not very protocol driven, so for him the key
things to monitor are appetite, attitude, level ofactivity and changes on body weight and condition over time. Many clinicians (including
Hughes & Howard) like to monitor haematology
and serum biochemistry every month to ensurethat all measurable abnormalities are improving,although this can be stressful for the patient andwww.theveterinarian.com.au

liver toxicity, so keep an eye on the ALP, ALT,
creatinine and SDMA, so be prepared to dose
adjust or discontinue therapy should nephroxicity or hepatotoxicity occur.
What about the kitten with multifocal CNS disease, where CNS FIP is the most likely cause of
the clinical signs? The traditional approach isserology (to try to exclude cryptococcosis andtoxoplasmosis), a good dietary history and trialof thiamine to rule out thiamine deficiency, then
MRI scans (Figure 10) and a CSF tap for fluid
analysis and multiplex neuroPCR analysis). Thisapproach is very expensive and there is also a
finite risk from the anaesthesia and especially
CSF collection. We have found that 3-5 days ofIV or SC remdesivir therapy can be used as a
cost-effective therapeutic trial in cats with likely
CNS FIP and is a cost-effective alternative tothe full diagnostic work-up which might cost
$3-5,000, or more.
Likewise, if the choice is an exploratory laparotomy, biopsy of abnormal tissues, histology, andimmunohistochemistry for FIP antigen to diagnose dry intraabdominal FIP versus a 3–5-daytrial of remdesivir, the latter might be considered to be better option in terms of both welfare
and reduced cost. In most cats with non-effusive‘dry’ FIP – there is a prompt improvement withantiviral therapy, with normalisation of fever,improvement in appetite and better overall attitude within 2 – 3 days. If the patient fails to
respond to remdesivir therapy, then of course
exploratory laparotomy and biopsy of representative organs is sensible, as the major DDx are
lymphoma and lymphocytic cholangitis.
This is a matter of every clinician’s personalstyle. A FNA for cytological and sometimes
immunohistochemical assessment or PCR iscogent non-invasive option where this expertiseis available, but sometimes this does not give adefinitive answer. Some veterinarians insist on
getting a tissue diagnosis and positive immuno-

Conclusions
In the past, a diagnosis of FIP was an intellectual
exercise, so we could end a cat or kitten’s miserywith the certainty of an accurate diagnosis. Now,
because of Niels Pedersen life-time studies of
FIP, we are in a position to successfully treat
perhaps 80 per cent of cats with FIP, if the client
has sufficient finances. Its too early to say how
many of these will later recur.
There is a huge learning curve to the diagnosis
and management of cases, but with effort, agood GP vet should be able to work with adiligent owner towards obtaining a clinical cure.
The most important thing is to not place too
many obstacles in the way of a committed owner,
and to support them through the 12-week
marathon treatment course, by helping themfind the best way to medicate their patient. Thismight involve a sedative/analgesic regimen to
help make the cat more tractable and prevent
discomfort, having the client bring their cat tothe clinic daily for remdesivir injections, managing hiccups along the way such as seizures
and providing a payment plan that will let thetreatment be affordable for a committed client.
It is incredibly satisfying to see cats andkittens that are unwell turn the cornerand become normal. It really is somethingthat lifts your spirits as a clinician. It isgood science and good veterinary medicine,and it is good for your soul!

Finally, the impact of COVID-19 on coronavirus
research has been profound, and there are several very promising drugs in development thatwork on most coronaviruses. It is highly likelythat some of these will be useful for treating FIP
in cats, and some of these drugs can be given
orally rather than parenterally. Interestingly weare aware of GS-441524-like drugs available in
China and eastern Europe as a cost-effective
capsule or tablet9 that is suitable for use in somecats with FIP – which might make therapy easierfor many owners in the future.
References
1. Kim, Y.; Liu, H.; Galasiti Kankanamalage, A.C.;
Weerasekara, S.; Hua, D.H.; Groutas, W.C.;
Chang, K.O.; Pedersen, N.C. Reversal of the progression of fatal coronavirus infection in cats bya broad-spectrum coronavirus protease inhibitor.
PLoS Pathog. 2016, 12, e1005531.
2. Pedersen, N.C.; Kim, Y.; Liu, H.; Galasiti
Kankanamalage, A.C.; Eckstrand, C.; Groutas,
W.C.; Bannasch, M.; Meadows, J.M.; Chang, K.O.
Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious
peritonitis. J. Feline Med. Surg. 2018, 20, 378–392.
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Figure 11: Two cat with dry FIP after successful therapy. As a keen young vet told me by e-mail notso long ago – “this is why I did vet science!” The Devon Rex is called Skimbleshanks (the Railwaycat) and is owned by Rose Jackson, a veterinary nurse. The Oriental cat “Milo” was treated by
Jessica Green at VetHQ Darlinghurst

3. Murphy, B.G.; Perron, M.; Murakami, E.;
Bauer, K.; Park, Y.; Eckstrand, C.; Liepnieks,
M.; Pedersen, N.C. The nucleoside analog
GS-441524 strongly inhibits feline infectious
peritonitis (FIP) virus in tissue culture andexperimental cat infection studies.
Vet. Microbiol. 2018, 219, 226–233.
4. Pedersen, N.C.; Perron, M.; Bannasch,
M.; Montgomery, E.; Murakami, E.; Liepnieks,
M.; Liu, H. Efficacy, and safety of the nucleosideanalog GS-441524 for treatment of cats withnaturally occurring feline infectious peritonitis.
J. Feline Med. Surg. 2019, 21, 271–281.
5. Dickinson PJ, Bannasch M, Thomasy SM, et al.
Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinicallydiagnosed neurological feline infectious
peritonitis. Journal of Veterinary Internal Medicine.
2020. doi: 10.1111/jvim.15780.
6. Tasker S. Diagnosis of feline infectious peritonitis: Update on evidence supporting available
tests. Journal of Feline Medicine and Surgery.
2018;20(3):228-243. doi:10.1177/1098612X187
58592
7. McDonagh, P.; Sheehy, P.A.; Norris, J.M.
Identification and characterisation of small molecule inhibitors of feline coronavirus replication. Vet. Microbiol. 2014, 174, 438–447.
8. Yuan, S., Yin, X., Meng, X. et al. Clofazimine
broadly inhibits coronaviruses including SARSCoV-2. Nature (2021). https://doi.org/10.1038/
s41586-021-03431-4
9. Addie DD, Covell-Ritchie J, Jarrett O, Fosbery
M. Rapid Resolution of Non-Effusive Feline
Infectious Peritonitis Uveitis with an Oral
Adenosine Nucleoside Analogue and Feline
Interferon Omega. Viruses. 2020 Oct
27;12(11):1216. doi: 10.3390/v12111216. PMID:
33121021; PMCID: PMC7693373.

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