11 Jun 2024
A cat with FIP being treated with antivirals but also fluid therapy and with an O-tube in place for nutrition.
In the UK, antivirals with high efficacy in the treatment of FIP have been legally available since 2021 (initially remdesivir and subsequently, its active form GS-441524). In that time, we have gained experience in managing the disease and monitoring treatment, and seen excellent outcomes.
Legally available sources of antivirals effective for FIP now exist in many other countries, although in some parts of the world, sadly, no quality-assured, legally available supply remains.
This article summarises the current advice on treatment of FIP to aid practitioners managing these cases and is based on current available information; however, the information will likely change as more experience and publications become available. It includes information on the recently available additional antiviral EIDD-1931 (the active form of molnupiravir). Treatment needs to be tailored to the individual cat based on response, compliance and client finances.
For more information on making an FIP diagnosis, view “Further Reading” at the end of this article.
Legally available antivirals in the UK and other countries via import now include remdesivir (injectable), GS-441524 (oral suspension and oral tablets) and EIDD-1931 (oral tablets). The following advice is based on published and unpublished data, and experience.
Treatment of individual cases remains the responsibility of the attending veterinary surgeon. The following dosages are based on experience using reputable preparations of known antiviral content. Extrapolation is not applicable to other oral preparations where the active component and/or its content are not known or provided by the manufacturer.
Oral GS-441524 (available as a suspension 50mg/ml and tablets of 25mg or 50mg) can be used from the start of FIP treatment for the entire treatment course (for example, 12 weeks/84 days; see section on duration of treatment courses).
It is important to support owners in medicating their cats, which can be challenging. Oral GS-441524 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 review the effect of food on absorption, but it is recommended to give in a small treat or on an empty stomach, leaving a gap of an hour or more before feeding a larger meal.
Fasting cats overnight can increase their hunger to facilitate medicating in the morning, and similarly for an evening dose. However, starving kittens is never recommended, as they cannot cope with this. Any withholding of food needs to be tailored to the age of the cat.
Injectable remdesivir (10mg/ml) is effective in the treatment of FIP, but is associated with some side effects (see section on side effects) – particularly pain on SC injection, which is seen in 50% of cats.
Previous FIP treatment protocols suggested this be used at the start of treatment before transitioning to oral GS-441254. However, we now know that FIP cats can be treated successfully with oral GS-441524 from their first day of treatment. This avoids pain on injections and reduces the costs of the treatment (dose for weight of cat for GS-441524 is cheaper than remdesivir).
Use of injectable remdesivir should be reserved for the following situations:
In some circumstances, if a cat is hospitalised and has a poor appetite that is affecting the ability to medicate it, 48 hours of remdesivir (given intravenously, not subcutaneously) can result in significant clinical improvements, which might facilitate subsequent oral medication with GS-441524. The remainder of the treatment course can then be given as oral GS-441524.
The transition between remdesivir and oral GS-441524 can be immediate; that is, from one treatment to the next.
Recommendations have usually been to treat for 84 days/12 weeks minimum, and most of the authors’ experience is with 12-week courses. However, we know that cats have been successfully treated with shorter courses of oral GS-441524 (at 15mg/kg by mouth once a day) for 42 days/6 weeks (personal communication; Hartmann, Hofmann-Lehmann and Gunn-Moore).
Publications are in preparation for these shorter courses, but the knowledge of these studies, and the reduced costs associated with 6 weeks compared to 12 weeks of treatment, means we should also consider them if appropriate for the patient. Further study is needed to learn about the experience and reported outcomes for different durations of treatment.
If treated cats respond rapidly, with resolution of clinical signs (including effusions) and normalisation of biochemistry abnormalities (and, if available, normalised serum alpha-1 acid glycoprotein [AGP] levels at four and six weeks), the attending clinicians could consider stopping and monitoring the cat carefully for possible relapse.
This would include (if available) checking AGP and/or biochemistry four weeks after stopping treatment, increasing confidence of remission if results remain normal. AGP is not available in many countries, and it might be that serum amyloid A can be used similarly, but further studies are needed. Communication with owners should discuss that, currently, most published response rates and outcomes are for cats treated for 12 weeks.
With experience and as yet unpublished data on therapeutic drug monitoring (TDM), dosage recommendations have increased from previous FIP treatment protocols. However, one must remember that published evidence shows more than 85% of cats respond to the previously recommended drug dosages, which is still a great response.
Based on TDM studies, we also now know that individual cats vary in their absorption of oral GS-441524, with those absorbing poorly likely requiring higher dosages to achieve clinical and biochemical remission. It is important that dosage of oral GS-441524 is adjusted according to clinical response, given these variations in absorption and limited availability of TDM to guide treatment.
Based on our collective experience, our current dosage recommendations are the following:
| Table 1. Recommended dosages for GS-441524 and remdesivir based on clinical presentation | ||
|---|---|---|
| Clinical presentation | GS-441524 by mouth dosage | Remdesivir IV or SC injection dosage |
| Effusion(s) and without ocular or neurological signs | 15mg/kg every 24 hours or split every 12 hours | 10mg/kg to 15mg/kg every 24 hours |
| No effusion and without ocular or neurological signs | 15mg/kg every 24 hours or split every 12 hours | 12mg/kg to 15mg/kg every 24 hours |
| Ocular signs present (with or without effusion) | 15mg/kg to 20mg/kg every 24 hours or split every 12 hours | 15mg/kg every 24 hours |
| Neurological signs present (with or without effusion) | 10mg/kg every 12 hours | 20mg/kg every 24 hours |
| Cats should be re-examined after one to two weeks (and sooner if not improving or deteriorating) and dosage adjusted depending on monitoring results at this point (see section on monitoring). | ||
It is very important to weigh cats weekly during treatment, using accurate scales (such as cat or baby scales). Weight gain and/or growth in kittens will occur with successful treatment, necessitating an increase in dose to ensure the dosage of antiviral administered is still appropriate for the type of FIP being treated (adjusted according to the individual cat’s response).
Failing to increase dose as the kitten grows appears to be a common cause for poor response to treatment and treatment failure.
TDM is available currently at The University of Edinburgh. Cats are sampled after three to five doses of starting the oral GS-441524. Ideally, 1.5ml serum and 0.5ml ethylenediamine tetra-acetic acid should be taken at peak (2 to 3 hours post-dose) or trough (9 to 12 hours post-dose) times after GS-441524 is given. This can be combined with AGP measurement. Email Rachael Hammond via [email protected] for information on submission. Results can allow adjustment of GS-441524 dosage or frequency of administration.
In the first two to five days, you should see an improvement in demeanour, appetite, resolution of pyrexia and reduction in abdominal or pleural fluid (if present).
More clinical signs attributable to FIP might be seen during the initial few days of treatment; that is, before the medication has had time to take effect. This can include development or recurrence of pleural fluid, which might require drainage (if the cat is at home, advise the owner to measure resting respiratory rate and respiratory effort). Neurological signs or uveitis may also develop (for example, owners might notice a change in iris colour). If neurological or ocular changes are noted, the drug dosage should be reviewed in case an increase is indicated.
Effusions usually resolve by two weeks. If an effusion is still present at two weeks, consider increasing the dosage (by 5mg/kg/day to 10mg/kg/day, and consider splitting into twice-daily doses if treated orally once daily).
Serum albumin increases and globulin decreases (that is, they normalise) might take several weeks, but note that globulins can initially increase when a large volume effusion is absorbed. In some cases, globulins might remain mildly increased, even at the end of a successful treatment course, and this mild hyperglobulinaemia has not been associated with relapse in our experience, if all other parameters have normalised.
Lymphopenia and anaemia might take longer to resolve – up to 10 weeks. A lymphocytosis (and eosinophilia) can also occur during successful treatment.
Enlarged lymph nodes typically reduce in size over a few weeks of treatment, but in some cases they do not return to normal size nor normal ultrasonographic echogenicity – even by the end of treatment. However, this does not seem to signify FIP relapse if all other parameters have returned to normal; treatment can be stopped as planned and the patient monitored.
If progress is not as expected, consider reviewing the diagnosis and/or increasing dosage. Occasionally, other antivirals can be considered.
Response rates are around 85%, with cats that respond rapidly (for example, returning to completely normal within 30 days) having a better overall response.
Some cats fail to respond to antiviral treatment, often deteriorating in the first two weeks; some cats might be too sick for the antivirals to work (although consider IV remdesivir in sick cats that cannot be medicated otherwise). Relapse is uncommon (less than 10%), but tends to occur in the first few weeks after stopping treatment.
Using therapeutic drug monitoring to inform dosing, and/or higher dosages, might result in higher response rates. Survival times are long (although we are all still learning about this), with late relapses (or reinfections) rarely reported.
Since the drugs have only been available since late 2021, we do not yet know if cats that appear to be cured stay that way life long, but result so far are very encouraging.
In some situations, it is not possible to achieve a definitive diagnosis of FIP due to cost constraints, availability of testing or instability of the patient precluding invasive testing.
Antiviral treatment trials can be considered using an appropriate dosage and objective measures to identify improvement; for example, serial neurological or ocular examinations. Improvements in demeanour and return of normothermia are expected within 48 hours, and add confidence to the presumed diagnosis of FIP.
Note that effusions can take longer to resolve (see section on what to expect in cats during treatment), and improvements in haematology and biochemistry abnormalities can also take weeks. Failure to improve on an adequate dosage of antivirals should prompt investigation for an alternative diagnosis. Most cats are notably better by 2 to 5 days, while a small number of cats can take up to 10 days; however, some positive signs have usually been seen before then.
Clinical response is most important to monitor; a failure to improve might necessitate an increase in dosage. Monitoring should be adequate to assess response, but, particularly when the cat is doing well, repetition of costly tests that are unlikely to alter treatment (for example, limiting testing to previously abnormal parameters and basic screen) and multiple, potentially stressful clinic visits should be limited.
Owners should be encouraged to weigh their cat at home (for example, using inexpensive baby scales) and keep a diary of appetite and demeanour, respiratory rate and other parameters as indicated.
The following recommendations will change depending on the cat’s response to treatment:
Once treatment is completed (usually 12 weeks’ duration, but evidence emerging of success with 6 weeks of treatment in selected cases; see previous section), cats should be monitored for relapse by their owners, including loss of appetite, weight changes or other clinical signs.
The clinical signs of relapse might differ from those at initial diagnosis (for example, neurological signs in cats that previously had effusions). Ideally, the cat is examined approximately four weeks after stopping treatment. Monitoring AGP, if available, might provide reassurance if it remains normal. Any clinical signs should be promptly investigated.
Side effects for these drugs can include the following:
Cats with FIP might benefit from various types of supportive care. No specific supplements have been studied alongside antivirals, and multiple oral medications might not be optimal due to compliance (as well as additional costs). However, sick and dehydrated cats might require IV fluid therapy.
The following interventions can be considered depending on the case:
If, for example, recurrence or lack of resolution of effusion, pyrexia, development of new ocular or neurological signs, or persistent clinical pathology abnormalities occur, consider the following:
EIDD-1931 (the active form of molnupiravir) is another antiviral effective for the treatment of FIP in cats; although, our knowledge on its usage is much less than for GS-441524. The recommended dosage is 15mg/kg every 12 hours, and it is available in 60mg tablets for oral use.
Potential adverse effects include cytopenia – especially neutropenia; rarely pancytopenia – reduced appetite/nausea, increased ALT enzyme activity and potentially, renal compromise. Use of EIDD-1931 should, therefore, be reserved for the following scenarios:
Neutering is ideally performed from a month after treatment is completed if the cat has responded well. However, if leaving the cat unneutered is causing stress (for example, attempts to escape or distress for queens on heat) then neutering during treatment can be considered if the cat is doing well on treatment, with at least another two to four weeks of treatment remaining if possible. Measuring AGP (if available) to confirm it is normal before neutering can be reassuring.
No contraindication to routine worming or flea treatment for cats on GS-441524 or remdesivir exists. No information is available on response to vaccination of cats receiving treatment for FIP. Prospective studies are needed, but analysis of treated cases suggests that cats can be safely vaccinated after or during successful treatment without causing relapse of FIP.
Vaccination should be given as recommended for the cat depending on its environment and risk (see WSAVA or European Advisory Board on Cat Diseases vaccination guidelines). If urgent vaccination is needed during treatment due to risk of infectious disease then they should only be given if the cat is clinically well.
If veterinary visits and procedures are necessary, clinic stays should be minimised, and Cat Friendly Clinic protocols and handling implemented to reduce stress to the cat.
Combinations of feline interferon omega, polyprenyl immunostimulant and mefloquine have been used in the period following the end of treatment with GS-441524 (or remdesivir) in some cats; however, no evidence currently exists to suggest they are needed, as high response rates of more than 85% have been seen without these adjunct treatments.
Mefloquine has also been used to treat cats with FIP when cost constraints absolutely prohibit the use of a full course of, or increased dosage of, more effective antivirals such as GS-441524. Studies are needed to evaluate its effectiveness, but it should only be used when no absolutely no alternatives are available, as GS-441524 is known to be very effective.
