From fatal to curable to complicated: An update on treating feline infectious peritonitis

Presenting an upbeat lecture on the topic of feline infectious peritonitis (FIP) is a relatively novel (and welcome) sensation for Michael R. Lappin, DVM, PhD, ACVIM, professor of internal medicine and director of the Center for Companion Animal Studies at Colorado State University College of Veterinary Medicine and Biomedical Sciences. “This has been the most frustrating infectious disease of my whole life,” Lappin said during his Winn Feline Foundation–sponsored session at the Fetch dvm360® virtual conference. “And now, after 30 years [working as a board-certified specialist], we’re finally making some inroads.”

Offensive strategy: Antiviral compounds

Despite some promise shown with 3C-like protease inhibitor GC-376,¹Lappin says RNA transcription inhibitors (nucleoside analogs)—specifically GS-441524—are “where all the action is right now.” (Although it should be noted that Anivive Lifesciences, Inc., is working to gain FDA approval of GC-376 as a treatment for FIP.)

According to Winn, anecdotal evidence suggests that antiviral compounds have been used to treat and potentially cure thousands of cats worldwide. GS-441524, which is produced by Gilead Sciences, has demonstrated the most success, but it’s not available for veterinary use. The drug has become increasingly important in the world of human medicine of late. Lappin explained that GS-441524 is the biologically active compound in remdesivir (GS-5734), which is currently being used to treat patients with coronavirus disease 2019 (COVID-19). “This small molecule interferes directly with the replication process of some viruses,” he added, “including feline coronavirus.”

Lappin described the 2019 research² by Niels Pedersen, DVM, PhD, on the efficacy and safety of using GS-441524 to treat cats with FIP as “absolutely imperative reading” for those practicing feline medicine. He broke down the following highlights:

• 18 of the 26 cats that completed the 12-week trial were in remission for multiple weeks (and were still healthy at the time of publication in February 2019) after only 1 treatment.
• Of the 8 cats that relapsed, 7 responded to repeated treatment.
• In all, the trial produced 25 long-time survivors.
• Daily subcutaneous injections of 4.0 mg/kg for at least 12 weeks was determined to be the optimal dose.

Before you pop that champagne...

“So here we are,” sighed Lappin. “Now we’re all excited. We have 3C-like protease inhibitors and nucleoside analogs … but you can’t get them.” So while the title of his session, “From fatal to treatable” is true, reality is definitely more complicated.

Lack of access to approved drugs has put both clients and veterinarians in a precarious situation, as the black market remains the only option for now. According to Winn, several Chinese companies say they’ve developed products—which are currently marketed as “dietary supplements” to treat FIP—that are the same as or similar to nucleoside analogs. Their use in veterinary health care remains illegal in the United States due to FDA restrictions, but owners of cats with FIP are able to get them through online and nonveterinary sources (like members of the public referred through Facebook groups), says Winn.

As with all black market drugs there are issues to consider, said Lappin, including sterility and toxicity. Moreover, there’s no way of knowing for certain that the compound contains what it says it does, and price doesn’t always correlate with quality.

What’s a veterinarian to do?

Alas, there’s no easy, one-size-fits-all answer at the moment. “I have to leave that up to you and your clients,” said Lappin. While you may not be able to prescribe or dispense these potentially life-saving compounds, you can choose to partner with your clients to provide monitoring and support to cats receiving black market drugs. As to whether he would pursue these compounds for his own cats if he were a layperson, Lappin simply said, “I love my cats. I love my cats a lot.” (It should be noted that he refers to dogs as the “inferior species.”)

Lappin recommended a couple of online resources for learning more about how pet owners are taking treatment matters into their own hands. Facebook groups, he said, can be a great way to learn about what people who love their cats and hate this virus (and who don’t have their Drug Enforcement Agency or other veterinary licenses to think about) are doing. There’s a lot of information to glean from their indirect trials to inform conversations with your own clients, Lappin explained. (Editor’s note: Lappin specifically mentioned the group, FIP Warriors, but it has been removed by Facebook).

SOCK FIP is on his list as well. The nonprofit site, which features Pedersen’s work, can help you (and your clients) stay current on the issues and think through what’s involved with seeking out black market drugs, said Lappin.

Still, many veterinarians aren’t willing to partner with clients using nonapproved compounds, and many clients are unwilling or unable to pursue them (as the cost is not insignificant). For such cases, Lappin recommended reading a 2017 study on treating FIP with Polyprenyl Immunostimulant (PI).³While it isn’t a cure and more research is needed, of the 60 cats diagnosed with FIP and treated with PI:

• 16 survived more than 100 days.
• 8 survived more than 200 days.
• 4 survived more than 300 days.
• 2 survived more than 900 days.
• 1 survived 1829 days.

“They had some pretty good data,” said Lappin of the study. “Not all of the cats had the complete diagnostics, but if you look at Table 7 in the study, this would convince me that if I was going to treat a kitty and wasn’t going to use black market drugs, I would consider this one.” And the best part? It’s readily available online from VetImmune. He noted that the second part of Table 7 shows that concurrent use of glucocorticoids appears to shorten duration of survival, so he would “just give them the product, not steroids.”

Could we have other options in the future?

Lappin answered this question by pointing to 2019 research on the antiviral activity of itraconazole against type 1 feline coronavirus.⁴ “Something we use like crazy for fungal infections actually inhibits some coronaviruses,” he explained. “It needs a clinical trial, but it’s kind of cool to know we can kill these coronaviruses. In fact, SARS-CoV-2 (the virus that causes COVID-19) can be killed with really high doses of ivermectin—unfortunately in doses we can’t achieve. But the bottom line is that we can sometimes go from the petri dish to a clinical trial.”

Anti–feline tumor necrosis factor (TNF)-alpha monoclonal antibody has also shown promise as a treatment for FIP, added Lappin, referencing a 2016 study.⁵“FIP is an inflammatory disease, so I think things like this will be a part of our lives as we go further,” he explained.

Hate the pandemic, love the research

Lappin didn’t lose his optimistic spirit when touching on the fact that cats are susceptible to a certain other notorious coronavirus: SARS-CoV-2. “The fact that there are great studies going on right now to find the best ways to save people from COVID-19, hopefully that will spill over to help more cats,” he explained. “And, of course, the work that Niels Pedersen and others are doing in cats will hopefully help people. This truly is a One Health story.”

References

1. Pedersen NC, Kim Y, Liu H, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J Feline Med Surg. 2018;20(4):378-392. doi: 10.1177/1098612X17729626
2. Pedersen NC, Perron M, Bannasch M, et al. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg. 2019;21(4):271-281. doi: 10.1177/1098612X19825701
3. Legendre AM, Kuritz T, Galyon G, et al. Polyprenyl Immunostimulant treatment of cats with presumptive non-effusive feline infectious peritonitis in a field study. Front Vet Sci. 2017;4:7. doi: 10.3389/fvets.2017.00007
4. Takano T, Akiyama M, Doki T, et al. Antiviral activity of itraconazole against type I feline coronavirus infection. Vet Res. 2019;50:5. doi.org/10.1186/s13567-019-0625-3
5. Doki T, Takano T, Kawagoe K, et al. Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis. Res Vet Sci. 2016;104:17-23. doi: 10.1016/j.rvsc.2015.11.005

Sarah Mouton Dowdy is a freelance writer and editor in Kansas City, Missouri.