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Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524

Coggins SJ, Norris JM, Malik R, Govendir M, Hall EJ, Kimble B, Thompson MF. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524. J Vet Intern Med. 2023 Jul 13. doi: 10.1111/jvim.16803. PMID: 37439383. (Winn/EveryCat-funded studies, W21-006, and W21-018)

Feline Infections Peritonitis (FIP) has classically been considered a fatal disease of cats, however recent advances in medicine have resulted in the creation of several antiviral compounds that have led to prolonged survival in large numbers of cats. A variety of medication including remdesivir and its metabolite GS-441524, molnupiravir, GC376, and others have been shown to be effective in treatment of both wet and dry FIP. The aim of this EveryCat-funded prospective case-series was to document survival and describe the clinical course of cats with FIP treated with compounded remdesivir administered parenterally as monotherapy, with or without transition to compounded GS-441524 administered orally.

Cats were recruited for the study through various routes, including a laboratory that confirmed FIP cases and other platforms like conferences, webinars, and social media. The cats remained under the care of their owners and regular veterinarians during the study.
A convincing FIP diagnosis required supportive clinical signs combined with a positive result on tissue or effusion immunocytochemistry or PCR. Treatment was continued for a minimum of 84 days and at least 2 weeks beyond achievement of remission.

A total of twenty-eight client-owned cats with FIP were recruited to the study.

The original treatment protocol was an induction with 10 mg/kg remdesivir given q24h as a slow IV infusion on days 0, 1, 2, and 3. The maintenance phase used 6 mg/kg administered subcutaneously (SC) q24h for a minimum of 84 days total treatment or extended at least 2 weeks beyond achievement of remission. If ocular or neurological manifestations were apparent, a higher maintenance dosage of 10 mg/kg was utilized.

A second group received a protocol of higher dose remdesivir (15-20mg/kg) due to reduced treatment efficacy at lower doses.

After the release of compounded GS-441524 50 mg tablets in late 2021 (half-way through case recruitment), if continued treatment with remdesivir was impeded by difficulty administering daily injections, veterinarians could elect to transition cats to oral GS-441524 at the same dosage rounded up to the nearest half tablet (25 mg).

Two cats (8%) had extreme adverse reactions to injectable drug because of perceived stinging after subcutaneous administration of remdesivir. Mild injection site discomfort was reported in 13/25 (52%) of cats and mild localized injection site reactions observed in 5/25 (20%). All adverse reactions resolved on termination of injections. No adverse effects were observed in cats receiving GS-441524 tablets. Eosinophilia was observed in 13/25 cats (52%) that completed 12 weeks of treatment; this was not associated with clinical signs, and it is unclear if this was due to the drug or the disease.

Markers of treatment success included resolution of fever, caivtary effusions, and clinical signs of FIP in the first half of treatment and normalization of globulin concentration, and body weight gains in the latter half of the treatment period.

Twenty-four cats survived to 6 months (86%). Three cats died within 48 hours. Excluding these, survival from 48 hours to 6 months was 96%. Three cats required secondary treatment for re-emergent FIP. Remission was achieved in all 3 after higher dosing (15-20 mg/kg). The recurrence rate to 6 months for cats that achieved remission whilst receiving low-dose Remdesivir was 30% (3/10), compared with no recurrence for the high dose Remdesivir (n = 2) and Remdesivir/GS-441524 (n = 13) groups.

The authors ultimately concluded that “Parenteral administration of remdesivir and oral administration of GS-441524 are effective and well-tolerated treatments for FIP. Early emphasis on clinical, and later emphasis on clinicopathologic response, appears prudent when monitoring treatment efficacy.”

Further work in this area is needed, including establishing ideal doses, closing intervals, and length of therapy. While this study serves as a demonstration of the efficacy of these therapies, it does not definitively establish the ideal method of treatment of these cats. Additionally, newer FIP drugs are coming onto the market rapidly, and combination therapies or alternative therapies may be more useful than single agents. Further work building on this study may help to elucidate more treatment options for FIP. ~MJK

See Also
1. Murphy BG, Perron M, Murakami E, et al. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet Microbiol. 2018;219:226-233.
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;21:271-281.
3. Jones S, Novicoff W, Nadeau J, Evans S. Unlicensed GS-441524-like antiviral therapy can be effective for at-home treatment of feline infectious peritonitis. Animals. 2021;11:2257.