Dr. Niels Pedersen - Feline Infectious Peritonitis (FIP) Symptomatic Treatment Options (as of March 2019)

This article was written by Dr. Niels Pedersen and is posted with his permission to benefit owners and veterinarians.

FIP Treatment

Symptomatic treatment

Currently, no effective treatment is legally available for cats with confirmed FIP. Until new treatments can be approved and marketed, treatment remains largely symptomatic. A low to moderate dosage of prednisolone or prednisone (starting at 2 mg/kg, orally, once a day for two weeks and then 0.5-1 mg/kg indefinitely), coupled with a diet high in animal protein (e.g., 1/2 cooked chicken, turkey or rabbit and 1/2 a favorite commercial cat food) and much personal care, is the simplest and possibly most effective symptomatic treatment. 

Symptomatic treatment ultimately depends on the cat's immune system to cure the infection. Some cats may have mild or subclinical disease isolated to a single intestinal lymph node, which may be detected as an abdominal mass upon routine physical examination or spay operation. Cats with more severe clinical signs will often go into a more chronic and less severe stage of disease after several weeks.

As we gain more experience with treating rather than euthanizing cats when FIP is diagnosed, we begin to appreciate that a proportion of cats may survive for many weeks, months, and rarely a year or more. However, it is still fair to say that FIP is ultimately fatal to most cats if left to run its natural course. There are misconceptions about the value of removing fluid effusions. Cats with chest involvement and breathing difficulties can benefit greatly from removing pleural fluid. Chest fluid also tends to be slowly replaced, especially when cats are treated with prednisolone. Removal of abdominal fluid should be discouraged unless it is so massive that it interferes with breathing. Abdominal effusions tend to be rapidly replaced at the expense of body fluids and proteins. Owners can be encouraged to maintain symptomatic and palliative treatment for as long as weight and activity are maintained. This can be days, weeks, sometimes months, rarely a year or more. However, owners should be apprised of the extremely high mortality among cats with clinically active FIP.

There is some debate on whether certain non-steroidal anti-inflammatory drugs (e.g., TNF-alpha blockers such as pentoxifylline, thalidomide), specific immunomodulators (e.g., feline interferon omega, human recombinant alpha, or beta interferon), and non-specific immunostimulants (e.g., several plant- or microbial-based biologics) have any efficacy against FIP. Although an initial study with feline interferon omega indicated efficacy, a subsequent large double-blind and placebo-controlled trial showed no efficacy. Human alpha and beta interferon are also of doubtless benefit and are immunogenic to cats and will be ultimately destroyed by the resulting antibodies. A similar large-scale trial with pentoxifylline also showed it was non-effective against FIP.

Homeopathic treatments for FIP 

Homeopathy involves administering sub-toxic doses of substances, usually plant-based, which mimic the disease signs intended to be cured. Several websites offer various homeopathic medications for cats with FIP. They are diluted tinctures of various plant extracts. These extracts are expensive, and many desperate owners will be tempted to use them. One of these companies is in Australia -(http://www.naturalpaws.com.au/feline-infectious-peritonitis-fip-usefulinfo-112-false.html).

Non-specific immunostimulants 

The use of non-specific immunostimulants has been popular in veterinary medicine for decades, usually for treating specific signs of feline leukemia and feline immunodeficiencies virus infection such as anemia or low lymphocyte counts. There are occasional anecdotal reports of cats with "FIP" cured or their lives prolonged by such treatments. These types of immunostimulants include substances such as Staphylococcal A protein, ImmunoRegulin (Propriobacterium acnes), Acemannan (mucopolysaccharide extract of Aloe vera leaves), and Imulan (lymphocyte T-cell immunomodulator). There is no evidence that these biologics have any beneficial effect on actual cases of FIP. Puritan FP is a plant-based substance advertised for cats with FIP. It can be found at - http://www.greenpetdepot.com/products/peritan. Interestingly, advertised statements about the efficacy of Puritan for FIP conclude with the following statement – "The Food and Drug Administration has not evaluated these statements. This product is not intended to diagnose, treat, cure, or prevent any disease." People should also be aware that some of the anecdotes attesting to the efficacy of a certain product for FIP are deliberately posted. Furthermore, many of the cats described may never have had FIP in the first place. An extract of tree leaves is the most popular non-specific immunostimulant touted on the web to treat cats with dry FIP. Polyprenyl immunostimulant (PI) (https://vetimmune.com/pi-product-information/) is classed as a biologic by the USDA and is manufactured by Vetimmune (https://vetimmune.com/) (formally Sass and Sass, Inc.). The USDA has given PI a conditional license as therapeutic for "symptoms" of feline herpes virus infection. Although not currently approved for treating FIP by the USDA, it is widely used off-label for prolonging the life of cats with milder forms of FIP. As a potential treatment for cats with FIP, Polyprenyl immunostimulant has an interesting history that extends from Russia to the United States. PI's research and chemical structure is based on a biological "plant extract" called Phosprenyl, which is used in Russia to treat a wide range of viral infections in many animal species (http://www.2ndchance.info/fip-gamavite.pdf. The first publication on the use of PI for FIP outside of Russia was an article (http://www.vet.utk.edu/research/fip/FIPpolyprenyl.pdf) published by Dr. Al Legendre and colleagues. This study treated three cats with subclinical dry-form FIP with Polyprenyl Immunostimulant. Two of the three cats were alive and well two years after diagnosis. The results from these three cats were used to justify a much larger treatment trial on 58 cats presenting solely with dry FIP. The results of this study were presented in 2012 at the ACVIM Forum. Twenty-two percent were alive for at least 165 days, and three cats lived longer than 365 days (5%), which was longer than expected. However, this study was faulted for not including a placebo control group and was subsequently published in more detail and including a historical control group -  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306384/. This report described 60 PI-treated cats with dry FIP and 59 cats with similar dry FIP from the literature that had not been treated. Eight of the 60 cats survived over 200 days, and 4 of the 60 survived over 300. No historical control cat that suffered solely from dry FIP and was not treated with PI lived longer than 200 days. 
The conclusion was that PI treatment prolonged the life of cats with the dry form of FIP. The published results with PI are difficult to interpret, but it can be safely concluded from the researcher's words that cats with wet FIP are not responsive to treatment and that there may be a small increase in survival time for cats with the milder dry form of FIP. It is also important to note that the USDA has not added FIP to its list of approved diseases for PI treatment and that the makers of PI do not promote its use for FIP. However, it has gained a vocal following on the web, generating a considerable market for treating FIP. PI may cost over $400 a month if used on an average size cat and dosed accordingly, and associated veterinary expenses can magnify this expense.

Non-specific anti-viral drugs 

Common drugs such as cyclosporine, cholesterol inhibitors such as itraconazole, various antibiotics, and several herbal extracts inhibit the FIP virus in cell culture. However, the anti-viral effect is weak, and the potential toxicity is great. These substances have their biological effects by inhibiting the normal metabolic processes of cells, and some of these processes are usurped by viruses to aid their replication. The amount of drug required to achieve the needed level of virus inhibition would be toxic or damaging to the cells and, thus, to the host cat.

Targeted anti-viral drug therapy  

The current hope for treating FIP rests with several of the same types of specific anti-viral drugs used to treat human viral infections, such as hepatitis C and HIV/AIDS. These are small molecules that are readily absorbed into cells and specifically target viral proteins essential for virus replication. Their toxicity for non-viral processes (i.e., cellular functions) is extremely low, making them safe and efficacious. We have described our laboratory and field experiences with GC376, a viral protease inhibitor, in an article in the Journal of Feline Medicine and Surgery. An abstract of this article can be accessed at the PubMed website (https://www.ncbi.nlm.nih.gov/pubmed/28901812). Anivive has obtained the rights for GC376, and they are starting the lengthy process of obtaining FDA approval for treating cats with FIP and eventual marketing - https://www.k-state.edu/media/newsreleases/2018-09/fipantiviral92018.html. 

We published our initial research studies on a second compound (nucleoside analog GS-441524- Gilead Sciences, Inc.) in 2018. These results can be found at the Veterinary Microbiology journal open access article website - (https://www.sciencedirect.com/science/article/pii/S0378113518301603). The successful testing of GS-441524 in owned cats with various forms of naturally-occurring FIP has just appeared in the Journal of Feline Medicine and Surgery - https://journals.sagepub.com/doi/full/10.1177/1098612X19825701. 

Similar reports will be forthcoming as other drugs undergo experimental and field testing. We are convinced, based on our research, that anti-viral drugs of the type currently used for HIV/AIDS and Hepatitis C virus (HCV) infection, and in the test phase for Ebola, Marburg, MERS, SARS, and bat coronavirus infections will provide the best chance for curing this terrible disease of cats. These drugs include protease inhibitors, nucleoside analogs, RNA polymerase inhibitors, and other anti-viral drugs that might target specific aspects of RNA virus replication.

Unfortunately, the research phase for these drugs has ended, no more field trials are contemplated, and no drug is legally available for veterinarians or owners. The processes involved in getting these new drugs FDA-approved and commercialized are long, and it may be 2-5 years before these or similar drugs find their way to veterinarians for use in treating cats with FIP. This delay has created a vigorous and growing black market for drugs like GC376 and GS-441524. GC376 is being illegally produced in China and sold through subsidiaries in Europe and the US. GS-441524 is also being produced illegally in China but has not yet appeared on the market. Manufacturers and secondary suppliers state that these drugs should be used for research purposes only and not for veterinary or human applications. However, they are well aware of the great demand and willingness of many cat owners to pay an extremely high price for them. 

We have no idea of these black-market compounds' purity or biological activity, and veterinarians have no experience preparing them for treatment or using them to treat cats with FIP. The treatment period for naturally occurring FIP is at least 12 weeks, not two weeks, based on treating cats with experimental FIP. Many owners have spent thousands of dollars on black-market drugs and have had to stop treatment before this time, even though their cats are responding due to the cost. The FIP will relapse if treatment is stopped too soon. Owners and veterinarians using should also be aware of possible legal and ethical consequences arising from the use of black-market drugs.