FIP: so much has changed, where are we now? (2024)

Dr Samantha Taylor BVetMed(Hons) CertSAM DipECVIM-CA MANZCVS FRCVS

Internal Medicine Specialist
Lumbry Park Veterinary Specialists

Sam is an RCVS Recognised Specialist in Feline Medicine, European Specialist in Veterinary Internal Medicine and a Fellow of the RCVS. She has worked in both University and private referral practice and is currently the Specialist Lead for the International Society of Feline Medicine and Clinical Board and Residency Lead at Linnaeus. She is an honorary lecturer in internal medicine at the University of Surrey and set up the FIPadvice email service with other specialists which has answered over 1200 emails about the novel treatments. She recently published a report on over 300 cats treated for FIP and continues to be involved in FIP research. 

This is a transcribe of the above treatment webinar recorded March 2024 by Dr Sam Taylor FRCVS

This webinar will provide practical information on how to use these drugs to best effect. So, a lot of the questions that, we get regularly asked on our FIP advice, and email service, which we’ve had over 2000 emails to, I’ve tried to cover in this talk because they’re areas that can be, a little bit challenging to understand, and especially as the advice often changes.

Let’s delve into the reasons behind this shift. Previously, we encountered a group of cats, some of which were featured in my earlier diagnostic discussion. These cats had been diagnosed with FIP. Past attempts to treat them involved medications like prednisolone, interferon, and polyprenyl immunostimulant. Unfortunately, these treatments were largely unsuccessful, resulting in euthanasia for most cases.

Fortunately, progress has been made since then. This advancement began with research conducted in the USA by Professor Pedersen, renowned for his work in FIP. He explored various drugs to treat the condition. Initially, he investigated protease inhibitors, which showed some effectiveness in treating certain cats. However, these drugs were not widely accessible.

Subsequently, he turned his attention to nucleoside analogues, which function by integrating into viral RNA to impede virus replication. In his initial studies, a majority of cats exhibited positive responses to this treatment in experimental and naturally occurring FIP cases. While there were relapses, insights were gained, such as the need for higher doses in neurological cases.

Following a pause in research, the focus shifted back to nucleoside analogues due to the COVID pandemic. This renewed interest led to the legal availability of these drugs for FIP treatment in cats from 2020. As of 2024, we are fortunate to have quality-assured drugs accessible in many countries globally. Let’s discuss these nucleoside analogues, the most well studied drugs for FIP treatment.

The first drug is remdesivir, known for its use in treating human COVID patients. While the veterinary formulation differs from the human version, some countries may still use the human product. The veterinary version boasts a higher pH level compared to the acidic human product, reducing injection discomfort.

Now, remdesivir undergoes metabolism to GS, commonly referred to as GS-441524. Though not the most catchy name, it’s firmly etched in my memory due to its effectiveness in treating FIP. This drug is now available in oral form as tablets and suspension, with its accessibility varying across different countries over the past three years.

• GS-441524 is offered in 50 mg tablets, which can be divided or crushed without any issues. Additionally, there is preliminary evidence, though unpublished, suggesting that the liquid form may be better absorbed than tablets, according to research at Edinburgh University.
• When administering this medication, it is generally recommended to take it on an empty stomach. The impact of food on absorption has not been extensively studied, but it can be given in a treat or small amount of food.
• Following the availability of Remdesivir, oral GS-441524 was introduced, leading to remarkable recoveries reported by early Australian users. The transition from injectable to oral drugs was welcomed, as daily subcutaneous injections were challenging.
• Initially, treatment dosages were based on Pedersen’s work, but higher doses have proven to yield better responses, prompting dosage guideline adjustments. This evolution in dosing guidelines, though potentially confusing, has been widely shared globally, thanks to collaboration among various countries.
• There was an initial recommendation to begin treatment with remdesivir before switching to oral GS, especially for severely ill patients who may not tolerate oral medications well or require rapid entry into the central nervous system.
• While the use of remdesivir initially may have advantages, such as parenteral administration for cats unable to eat or severely ill patients, many cats are successfully treated with oral GS-441524 from day 1.

One advantage of starting treatment with remdesivir is the quick improvement in demeanour and appetite, making it easier for pet owners to administer medication. Here are some key points to consider when using remdesivir for FIP treatment in cats:

• Giving one or two doses of remdesivir can lead to noticeable improvements in hospitalized cats.
• When administering remdesivir intravenously, it is important to dilute it and give it over approximately 20 minutes to reduce potential adverse effects like hypotension.
• Subcutaneous administration of remdesivir may cause some discomfort due to its pH, even with the veterinary product.
• While remdesivir is still a valuable treatment for FIP in cats, many cats are now treated with oral GS-441524 from the beginning of treatment.
• It is acceptable to use GS-441524 for the entire treatment course if cats can be medicated orally and are deemed well enough.
• Crushing GS tablets or adding the suspension to liquid treats can facilitate the administration of the medication.
• Consider fasting cats briefly before medication to make them more receptive to taking the medication, especially in the morning and evening.
• For cats with grazing habits, limit the fasting period to ensure they do not go without food for too long, particularly if young cats or kittens.
• Initial dosage recommendations for remdesivir.GS-441524 may vary based on location of the FIP, with higher doses often needed for cats with neurological and ocular FIP.

It is a common challenge for many drugs to reach the CNS, leading to a need for higher doses to achieve the desired levels in target areas. Our study, which involved over 300 treated cats, revealed significant individual variations in response.

Absorption of oral GS varies significantly among cats, with some cats excreting it rapidly, resulting in lower blood levels than desired. During our research, we observed that some cats responded well to lower doses, while others required higher doses, leading to a wide range of prescribed doses.

Dosage adjustments were common among the cats we studied, highlighting the need for individualised dosing. While some cats may receive higher doses than necessary, positive initial responses often correlate with better outcomes. Starting with a sensible higher dose is likely to elicit a positive response in most cats.

Our recommendations have evolved to include twice-daily oral GS administration, as it better maintains optimal serum levels compared to once-daily dosing. However, compliance challenges exist, and if a cat responds well to once-daily treatment, there may be no need to switch.

For neurological and ocular cases, higher dosages are typically used, and while some effusive disease cases may require doses similar to those used for neurological issues, many respond to a lower dosage. Regular re-evaluation of cats is essential, with dosage adjustments being made if there is no improvement or deterioration is observed.

The recommended treatment duration of 12 weeks is based on research suggesting that coronavirus residing in macrophages necessitates an extended treatment period. While some cats may respond to shorter courses, treating for 12 weeks is advised for now, pending further research developments.

In cases where financial constraints limit treatment duration, treating the cat for as long as possible within their means is recommended to maximize their chances of recovery, while adhering to current treatment guidelines.

Treatment Duration and Monitoring Guidelines for Cats with Feline Infectious Peritonitis (FIP)

• Some cats may require treatment beyond 12 weeks due to relapses or poor responses, necessitating an extended treatment period. Owners should understand this commitment and not cease treatment solely based on clinical improvement.
• Certain cats may respond exceptionally well and rapidly, possibly indicating a shorter treatment duration would be successful but more research is needed. Implementing testing to predict such cases is under development.
• Advising clients to continue treatment for 84 days remains a prudent recommendation.
• Expect rapid clinical improvement with remdesivir or oral GS treatment, typically noticeable within the first few days in terms of resolving fever, and becoming brighter, and improved appetite. Other improvements, such as resolving effusions or anaemia, may take longer.
• Pleural effusions may require multiple drainages over a couple of weeks. This is not an adverse effect of medication, but time is needed for it to become effective and vasculitis to reduce.
• Monitoring effusions can be done by measuring the cat’s girth or using ultrasound to assess fluid levels, with improvements anticipated within a few weeks.
• Anaemia resolution may take two to three weeks, while normalization of globulin levels, affecting the A:G ratio, could take several weeks.
• Lymph node changes in cats with non-effusive FIP may gradually reduce over several weeks, with some cases showing lingering abnormalities post-treatment.
• Monitoring progress involves observing clinical signs, temperature normalisation, and improvement in demeanour and appetite, with globulin levels potentially being the last to normalize.
• Regular check-in points with owners, such as improvement after a couple of days and follow-up after two weeks, are crucial, and tailored to each cat’s needs and owner’s abilities.
• Periodic examinations, weight checks, effusion measurements, and blood tests are recommended at specific intervals to evaluate progress and adjust treatment accordingly.

Before completing treatment, cats should be examined around 10-12 weeks to ensure abnormalities have resolved:

• Monitor the cats regularly for changes in weight, especially as they may fluctuate during treatment and cats will gain weight and need dosage increases.
• Owners are encouraged to weigh their cats weekly at home to track progress effectively.
• Therapeutic drug monitoring is available in Edinburgh in 2024, allowing for precise measurement of GS levels in treated cats.
• Monitoring drug levels can help adjust dosages accordingly for optimal response.
• Adverse effects of medications have been minimal so far, with occasional increases in liver enzymes being the most common issue.
• Liver support medications may not be necessary unless the cat is very easy to medicate.
• Subcutaneous injections of remdesivir can sometimes cause pain and other skin issues, which can be managed with additional medications (gabapentin or pregabalin for example).
• Kidney issues have been rare, with only a small number of cats showing slight increases in creatinine levels.
• Hypotension after IV remdesivir and occasional diarrhoea with GS treatment have been reported, but further investigation is required to determine their underlying causes.
• In some cases, urinary stones containing GS-441524 have been found, linked to certain sources of GS with higher-than-expected levels.

Some products lack clear content information, unlike our legal products. It’s wise to ensure cats on GS stay hydrated and to monitor for urinary tract signs, even though it’s not a major concern at our recommended doses.

Deciding when to stop treatment can be tricky. At the 12-week check, everything should ideally be normal. However, some cats may show slight increases in globulin levels post-treatment, along with changes in lymph nodes and occasional static neurological signs. In such cases, it’s crucial to assess other factors like effusions, AGP levels, and the progression of neurological signs before making a decision.

If neurological changes remain stable such as mild ataxia at the end of the treatment period, one option is to consider increasing the dose and monitoring for progress, or stopping and watching for any relapse. In most instances with minor persistent globulin increases but otherwise normal results, relapses have not occurred.

Using objective measures is key when adjusting the dose to track changes accurately. In many cases, increasing the dose doesn’t lead to significant improvements, possibly indicating persistent inflammation without the organism, akin to long COVID in humans.

It can be challenging to decide when to stop treatment, but owners should understand that stopping when everything isn’t perfectly normal carries a risk of relapse. However, in most cases, as long as other aspects have improved and normalized, relapses are unlikely.

In cases of a suspected FIP diagnosis, treatment may vary based on the severity and confirmation of the diagnosis. If the cat is very ill with neurological signs and hospitalised, starting with remdesivir may be an option. The dosage will depend on the FIP’s location and can switch from IV to oral GS once the cat shows improvement. Adjusting the dosage according to the FIP location is crucial, and rounding up tablet sizes if needed is considered safe. Regular checks at 24/48 hours (eg over the phone with the owner to check how they are getting on with medication, has cat started to improve), two weeks, six weeks, and 12 weeks are encouraged for monitoring progress, but clinical signs and physical examination remain most important – tailor other tests to response and owner finances (eg total solids and PCV, measure effusion as a minimum).

If the response meets expectations, we will maintain the current dosage. However, I am hesitant to recommend reducing the dosage at this stage, depending on the response. There is insufficient evidence to support reducing the dosage for cats that have responded exceptionally well and have normalized parameters. This aspect could be explored further in the future, but for now, we will stick to the starting dosage.

If the response is inadequate, we will consider increasing the dose, provided we are confident in our diagnosis of FIP. Some cats in this category may have been misdiagnosed.

It’s worth noting that recent publications have analysed unofficial sources of GS-441524. Depending on your location and the availability of legal formulations, individuals may seek these drugs online. Access to legal drugs is expanding, but cost remains a concern. Although prices have decreased in certain countries due to import costs, they are still high, leading owners to explore online options. However, there are significant risks associated with purchasing drugs this way, such as unknown content and quality issues.

Some products may not even disclose the presence of GS in their labelling, claiming to contain other natural ingredients. An analysis revealed that most injectable products contained more drugs than stated and were highly acidic, with only a few meeting manufacturing standards. Similarly, oral GS products varied widely in content accuracy, making it challenging for veterinarians to adjust dosages effectively.

Legal constraints may prevent veterinarians from providing dosage advice in such cases, with potential legal ramifications for involvement with these drugs. It is crucial to educate owners about the importance of knowing the composition of administered drugs. Providing accurate information on these medications allows for informed discussions on expected responses.

Presenting data from a study by Taylor et al. in 2023, we observed an 85% response rate. This aligns with findings from other studies using legal medications. While most cats respond well to treatment, a small percentage may not, especially those that are severely ill or exhibit severe neurological symptoms.

For cats that do not respond to treatment, a thorough review of the diagnosis is necessary to ensure accuracy. Intensified support may be required for critically ill cats, including hospitalization and fluid therapy for conditions like hypotension and hypoglycaemia. Monitoring medication adherence at home is essential, and therapeutic drug monitoring can be beneficial. Adjusting the dosage by 2 to 3 mg per kg per dose (4 to 6 mg per kg per day) may be recommended, potentially extending the treatment course beyond the initial weeks. In line with our plans for 12 weeks, we may extend the course. Some cases could benefit from switching to an alternative antiviral medication that will be discussed shortly. If relapse occurs, approximately 5% of cats initially show positive responses but later relapse or show partial improvement before relapsing.

Cats that relapse may exhibit different clinical signs than their initial presentation. They could shift from neurological to effusive cases or vice versa. Stay open to various forms of relapse.

Our initial step will be to increase the dose and consider therapeutic drug monitoring if possible. We will maintain the higher dose based on the response. Some cats may relapse even after the 12-week treatment, typically within a few weeks, although rare cases may relapse later.

While long-term outcomes are still being studied, it is unlikely for cats to relapse years later. However, reinfection cannot be ruled out, requiring a restart of the treatment course at an increased dose if necessary.

In situations where a rapid response is not observed, we may consider alternative medications. Holistic treatment, including pain management, fluid therapy, nursing care, stress management, and nutrition, can potentially improve response – these are sick cats and need extra care to speed recovery – as well as anti-virals.

Additional medications can include:

• Specific ocular and neurological medications (anti-seizure drugs) may be required based on the condition.
• The use of corticosteroids should be approached with caution due to potential adverse effects and lack of evidence of any advantage.
• Antiemetics like maropitant, and appetite stimulants like mirtazapine can help the cat’s overall condition.
• Feeding tubes may be needed.
• Providing support and guidance to caregivers is essential to ensure successful treatment.
• Consider the challenges of giving medication to cats and explore alternative options like liquid treats.
• Monitoring and adjusting medication based on individual cat responses is crucial for effective treatment.
• New drugs like EIDD-1931 and molnupiravir show promise in treating FIP, but careful consideration and monitoring are necessary and currently reserved for cats not responding to GS-441524 or relapsing.

We can inform clients that there is limited published information available on the subject, but thorough studies are lacking. However, based on feedback received via our advice line, there have been no reports of cats experiencing relapses post-vaccination or neutering. Therefore, the recommendation is to tailor vaccinations according to each cat’s risk factors and adhere to current vaccine guidelines.

For instance, this may involve less frequent vaccinations for indoor cats. Many of these cats are under one year old, and by the time they finish their FIP treatment, they are due for their vaccinations, including the crucial one-year booster. It is advisable not to skip this vaccination due to its effectiveness against other diseases, even though extensive data is not available.

Neutering can potentially reduce stress levels, as evidenced by cases of FIP cats whose neutering was postponed, leading to increased frustration, inter-cat aggression, and conflicts at home. Therefore, it may be reasonable to neuter a cat undergoing FIP treatment towards the end of their regimen or shortly after completion. Ensuring a stress-free experience by following cat-friendly clinic protocols, such as using gabapentin or pregabalin before visits and discharging the cat promptly, is essential as stress impacts susceptibility to infections.

Witnessing cats with FIP recover successfully from treatment has been truly remarkable. In response to owners’ inquiries about the prognosis for their cats, the outlook is highly optimistic. While not every cat may have the same outcome, and we cannot promise all will respond, achieving an 85% or higher survival rate from previous challenges is a reason for great satisfaction.

Thank you for your attention. If you want to delve deeper into feline care, consider becoming a member of ISFM for comprehensive insights. The email for our advice line is available for further inquiries ([email protected])