Treatment of feline infectious peritonitis (FIP) in the UK - update of treatment protocols - what's new?

Original article: The treatment of feline infectious peritonitis (FIP) in the UK – an update FIP treatment protocols – what's new?; 02/2024

Sam Taylor BVetMed(Hons) CertSAM DipECVIM-CA MANZCVS FRCVS
Séverine Tasker BVSc BSc DSAM PhD DipECVIM-CA FHEA FRCVS
Danielle Gunn-Moore BSc(Hon), BVM&S, PhD, MANZCVS, FHEA, FRSB, FRCVS
Emi Barker BSc BVSc PhD PGCertTLHE DipECVIM-CA MRCVS
Stephanie Sorrell BVetMed(Hons) MANZCVS DipECVIM-CA MRCVS

We thank Richard Malik and Sally Coggins for their advice and assistance in the preparation of this paper.

Oral GS-441524 (available as a 50 mg/ml suspension and 50 mg tablets) can be used from the start of FIP treatment for a full (eg, 12-week/84-day) cycle. It is important to support owners in their cats' medication, which can be difficult. GS-441524 oral suspension or tablets can be given with a small treat (tablets can be crushed for this) or directly into the cat's mouth. Further study is needed to examine the effect of food on absorption, but it is recommended that it be given in a small treat or on an empty stomach, with an hour or more gap before a larger meal.

Fasting cats at night can increase their hunger to facilitate the administration of the medicine in the morning, and similarly for the evening dose. However, starving kittens is never recommended as they will not be able to handle it. Any withholding of food must be adapted to the cat's age.

Injectable remdesivir (10 mg/ml) is effective in the treatment of FIP but is associated with some side effects (see below), particularly pain on subcutaneous injection occurring in 50 % cats. Previous FIP treatment protocols suggested that this drug be used initially before switching to oral GS-441254. However, we now know that cats with FIP can be successfully treated with oral GS-441524 from the first day of treatment. This avoids injection pain and reduces treatment costs (the dose per cat weight using GS-441524 is cheaper than remdesivir). The use of injectable remdesivir should be reserved for the following situations:

• Severe neurological symptoms and inability to swallow or tolerate oral medications;
• Extremely dehydrated/unruly cats;
• Cats that cannot be treated orally for other reasons.
• In certain circumstances, if the cat is hospitalized and has decreased appetite, which affects the ability to administer medication, 48 hours of remdesivir (given intravenously, not subcutaneously) may result in significant clinical improvement that may facilitate subsequent oral treatment with GS-441524. The rest of the treatment cycle can then be administered in the form of oral GS-441524.

The switch between remdesivir and oral GS-441524 can be immediate, ie from one treatment to the other.

The current recommendation is to treat for at least 84 days. Some cats have been successfully treated with shorter courses, but large-scale case studies have not yet been published. If cost constraints require a shorter duration of treatment, the dose used should not be reduced and treatment should last as long as possible.

With experience and as yet unpublished data on therapeutic drug level monitoring (TDM), dosing recommendations have increased over previous FIP treatment protocols. However, evidence shows that more than 85 % cats respond to previously recommended drug dosing, which is still a high rate. However, based on TDM studies, we now know that individual cats vary in their absorption of oral GS-441524, with those that absorb it poorly requiring higher doses to achieve clinical and biochemical remission. Ideally, dosage should be adjusted based on TDM, if available (see below), or based on response to treatment.

Compared to previous FIP treatment protocols, the following changes in dosing recommendations are important:

• GS-441524 is administered orally in divided doses twice daily (every 12 hours) to optimize serum levels of GS-441524;
• Higher dosages may overcome malabsorption problems in some cats and have a better chance of crossing the blood-brain barrier and the blood-ocular barrier;
• Dosage should be adjusted according to response and TDM if available.

Cats should be re-examined after 1-2 weeks (sooner if not improving or worsening) and dosage adjusted depending on monitoring at this point.

NOTE ON WEIGHING CATS: During treatment, it is very important to weigh the cats once a week, using accurate scales, e.g. on cat or baby scales. With successful treatment, the kittens will gain weight and/or grow, necessitating an increase in the dose to ensure that the dose of antiviral given is still adequate for the type of FIP being treated according to Table 1. Failure to increase the dose as the kitten grows appears to be one of the most common causes poor response to treatment and treatment failure.

e.g. recurrence or insufficient resolution of effusion, pyrexia, development of new ocular or neurological symptoms, or persistent clinicopathological abnormalities:

• Make sure you are still sure the cat has FIP; reassess the diagnosis, seek further pathology and consider repeat sampling (eg, external laboratory analysis and culture of any fluid; cytology or lymph node biopsy ± detection of feline coronavirus antigen or RNA, but remember that with treatment the virus is more difficult to find), AGP;
• Consider TDM, if available, to monitor GS-441524 serum levels to inform dosing;
• If relapse occurs during treatment, increase the dose of GS-441524 (or remdesivir) by 2-3 mg/kg per dose and monitor as above, ensuring that treatment is not stopped before the cat is in normal clinical condition and based on clinical pathology results for at least 2 weeks. Dosage increases depend on the dosage the cat is receiving at the time of relapse, the nature of the relapse and financial resources, but can be up to the recommended dosage for neurological FIP (see dosage chart above) or even higher (seek advice when considering this option );
• If relapse occurs after stopping treatment, restart GS-441524 (or remdesivir) at a higher dose (at least 2-3 mg/kg higher than previously used) and ideally continue treatment for an additional 12 weeks. The increased dosage used will depend on the dosage the cat was receiving prior to the relapse and the nature of the relapse, but may be up to the dosage recommended for neurological FIP;
• If the cat is already on a high dose of GS-441524 and/or serum TDM levels are adequate, consider switching to EIDD-1931 (see below) and seek advice (email advice for FIP or specialists) as adjunctive therapy such as mefloquine feline interferon or a polyprenyl immunostimulant may be an option (see below).

This drug is another antiviral effective in the treatment of FIP in cats, although there is much less evidence of its use than GS-441524. The recommended dosage is 15 mg/kg every 12 hours and is available as 60 mg tablets for oral use. Potential adverse effects include cytopenia, especially neutropenia, rarely pancytopenia, decreased appetite/nausea, increased ALT enzyme activity, and potential renal compromise. The use of EIDD-1931 should be reserved for:

• cats that do not respond to treatment with GS441524 or remdesivir despite adequate dosing (ideally assessed by TDM);
• cats that relapse after treatment with GS-441524 or remdesivir at an appropriate dose.

• In some cats, combinations of IFN omega, the immunostimulant polyprenyl, and mefloquine were used in the post-treatment period with GS-441524 (or remdesivir); however, there is currently no evidence to suggest that they are necessary, as even without this adjunctive treatment, a high success rate of over 85 % has been reported;
• Mefloquine is also used to treat cats with FIP when financial constraints make it absolutely impossible to use a full course or increased dosage of more potent antivirals such as GS-441524. Studies are needed to evaluate its effectiveness, but it should only be used when absolutely no alternatives are available, as GS-441524 is known for its high potency.