Modern Treatment of Feline Infectious Peritonitis (FIP): Essential Information for Veterinarians

Recent breakthroughs in FIP treatment have dramatically improved the prognosis for affected cats. Discover how these advancements and newly available legal drug options are saving feline lives, and learn about the essential role veterinarians play in this evolving landscape.

Research Authors

Summary

FIP has historically been a fatal disease in cats, caused by a mutation in the feline enteric coronavirus. Advances in treatment with nucleoside analogues like remdesivir and molnupiravir have significantly improved survival rates. Studies show that 85% of treated cats now survive, particularly with early diagnosis and prompt treatment. The role of veterinarians is crucial in administering these treatments correctly and monitoring for resistance. Recent legal availability of these drugs in New Zealand provides a safer and more affordable option compared to previous black-market sources.

Background

Feline Infectious Peritonitis (FIP) is a common infectious disease of cats. This disease occurs when the feline enteric coronavirus acquires a mutation that allows multiplication within macrophages. Historically the marked inflammatory response that ensues was a life-ending disease.

Fortunately, there are now two nucleoside analogues available for cats in New Zealand that appear highly effective, remdesivir and molnupiravir. Nucleoside analogues are similar molecules to the ‘true’ nucleosides that are the building blocks of DNA and RNA. Because of their structural similarities, they interfere with key enzymes in DNA or RNA replication or are integrated into DNA or RNA strands, leading to chain termination or non-functional nucleic acids. One of the limiting factors is these analogues are not only used by viral enzymes but also by mammalian enzymes, which largely accounts for their potential toxicity.

The treatment of FIP has evolved significantly from the initial reports of success by Peterson et al in 2019 (1). This initial study investigated the use of GS-441524 in 31 cats with FIP. Overall, 80% of these cats survived long-term.  Four of the non-surviving cats were initially severely affected and were either euthanised or passed away in the initial days of the treatment regime.  The treatment regime in this study involved daily subcutaneous injections for 12 weeks. A small proportion of cats required repeat protocols following relapse. Considering this disease was almost universally fatal, long-term survival in 80% of cats is remarkable.

Legal Issues

GS-441524 has never been available as a legal treatment option for cats. This publication resulted in the establishment of a black market for GS-441524 around the world. This medication became surprisingly easy to order online, getting through the border disguised as cosmetics. As a result of this widespread use, some large studies are emerging on treatment outcomes. Jones et al (2) published the results of an online survey of the outcomes of almost 400 cats. There are some obvious limitations of an online survey, however, the results still provide some useful insights. Only 8.7% of owners reported receiving significant help from their veterinarian – no doubt due to the legalities of this. Almost 90% of the owners reported noticing improvement after one week. 12.7% of cats experienced a relapse, with only 3.3% of cats dying despite treatment.

As GS-441524 is not able to be obtained legally in New Zealand, its use cannot be supported. This is especially the case now legal options are available that are substantially cheaper than the black-market options. Remdesivir is a prodrug of GS-441524, that we now know is rapidly metabolised into GS-441542 in cats, so other than different dose rates they are very similar medications.

 

The Importance of Veterinary Involvement

As noted above, there are large numbers of cats that have been treated without veterinary support. This, and the ever-changing research provides opportunities for vets to help cats in the future. Veterinarians in New Zealand need to re-establish a central role in treating FIP as our knowledge and skills will help to ensure more cats are treated and survive long term. I think the main way we can do this as a profession is to keep up with the current literature and treatment protocols. As a result of these past events, there are large social media groups where owners are providing advice of variable accuracy. There are frequent comments by owners that their vet did not know about FIP treatment, which of course drives the owners to seek information elsewhere. While these groups are a great source of support, the treatment information provided by other owners is often out of date or incorrect. I hope that some of the insights below will help to start some more conversations.

Prognostic Factors

The severity of the clinical signs at presentation seems to be the biggest factor influencing survival with treatment. Overall, around 85% of treated cats will survive. If the cat survives the first week of treatment, this survival rate increases to over 95%. In a rapidly progressive disease, early diagnosis and prompt treatment are key. There are some very useful recent guidelines on how to reach a clinical diagnosis of FIP (3). Unfortunately, there is inevitably a delay in reaching a clinical diagnosis while awaiting histology, or a PCR (of effusion for wet FIP, or CSF for dry FIP). We routinely start treatment when we have a very strong index of suspicion of FIP while awaiting the results of the diagnostic tests. Treatment trials without diagnostic tests should be discouraged if possible as the development of resistance to these vital medications is a big concern. There has not yet been much investigation into the mechanisms of resistance development, but we do see it already. A small proportion of cats appear to be resistant to medications from the onset. More often we suspect resistance develops during treatment which can be partial requiring a higher dose, or complete. We have anecdotally observed a cluster of resistant cats from one location with dubious use of remdesivir which has raised some alarm bells.

Picture of a Birman kitten
Ollie, one of the adorable FIP cats treated at ARC

Remdesivir

Treatment protocols have changed significantly with time. Initially, we started parenteral remdesivir in every cat as the oral absorption was presumed to be poor. Subcutaneous injections at home for 12 weeks were a big challenge for most owners, especially as the solution is acidic, so stings when administered. The recommended starting dose has crept up with time as remdesivir was shown to be safe.  A study from UC Davis recently investigated the absorption of oral remdesivir, and it was found to be around 40 – 50%(4). So, the transition to oral doses has necessitated a doubling of the administered dose. Unfortunately, under-dosing remains a very big problem with both out-of-date doses administered, and parenteral doses given orally. There is concern this may lead to resistance to treatment.

ARC is currently offering two main treatment options for cats with FIP; starting with two weeks of injections, followed by 10 weeks of oral capsules, or oral capsules alone. It is unknown whether any parenteral treatment is needed. The pharmacokinetics of remdesivir have only been studied in healthy cats. We strongly suspect that sick cats, especially those with effusive disease, will have altered absorption of oral medications. We are currently evaluating the pharmacokinetics and treatment outcomes of these two groups.

Molnupiravir

Molnupiravir closely resembles GS-441524, but is an analog of cytidine rather than adenine. There are no published comparative studies comparing the efficacy of remdesivir compared to molnupiravir. The optimal dose of molnupiravir remains unknown. This medication has a narrower safety margin compared to remdesivir and higher doses seem more likely to result in severe leukopaenia and other adverse effects. There is currently one paper evaluating the use of molnupiravir in cats that noted broadly similar success rates and relapse rates to those published with remdesivir in 30 cats that had failed remdesivir (5). Remdesivir/GS-441542 has been in use for a longer period of time resulting in substantially more published literature, so this remains our current initial treatment of course. Fortunately, the costs of treatment have fallen dramatically recently, especially with the use of oral capsules. Per capsule, the cost of remdesivir is currently very similar to Molnupiravir. As Molnupiravir is usually a twice-daily medication, a treatment protocol is typically more expensive at the current prices. More information will come in the future, with comparative studies underway. However, with the current information available Molnupiravir is probably best reserved for treating cats that have failed remdesivir.

Monitoring

Monitoring during treatment is vital to help determine which cats need an increased dose, or duration of treatment. This is one of the areas veterinarians can help most.  One of the secondary aims of our research is to evaluate “milestones” that should be met during the treatment, so these can be used to help predict the response to treatment and make early adjustments. We routinely monitor for resolution of the clinical signs, effusions, and biochemical markers at roughly monthly intervals during and after treatment.

Cats with dry/neurologic/ocular FIP remain a challenge, both reaching a diagnosis and monitoring treatment. Dry cases tend to have much less dramatic (and often no) biochemical changes and will often retain some mild-moderate neurologic deficits even when cured which presents a challenge. We need a high index of suspicion for these cases to ensure they are promptly diagnosed. Fortunately, there is a relatively limited list of common differential diagnoses for neurologic signs in this signalment (i.e. young often purebred cats), with FIP being by far the most common diagnosis.

Help for Vets

Keeping up with the rapidly changing FIP literature can be challenging, but we are here to assist! Our internal medicine team welcomes referrals for FIP consultations and further treatment. Additionally, ARC offers free FIP phone consultations to veterinarians in New Zealand, providing the most up-to-date treatment advice as part of our studies. Please don’t hesitate to reach out.

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Citation Reference
  1.  Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. Journal of feline medicine and surgery. 2019 Apr;21(4):271-81.
  2. Jones S, Novicoff W, Nadeau J, Evans S. Unlicensed GS-441524-like antiviral therapy can be effective for at-home treatment of feline infectious peritonitis. Animals. 2021 Jul 30;11(8):2257.
  3. Thayer V, Gogolski S, Felten S, Hartmann K, Kennedy M, Olah GA. 2022 AAFP/EveryCat feline infectious peritonitis diagnosis Guidelines. Journal of Feline Medicine and Surgery. 2022 Sep;24(9):905-33.
  4. Cook S, Wittenburg L, Yan VC, Theil JH, Castillo D, Reagan KL, Williams S, Pham CD, Li C, Muller FL, Murphy BG. An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats. Viruses. 2022 Nov 1;14(11):2429.
  5. Roy M, Jacque N, Novicoff W, Li E, Negash R, Evans SJ. Unlicensed Molnupiravir is an effective rescue treatment following failure of unlicensed GS-441524-like therapy for cats with suspected feline infectious peritonitis. Pathogens. 2022 Oct 20;11(10):1209.