16.8.2024
Original article: Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study.
Complete clinical study: Zuzzi-Krebitz AM, Buchta K, Bergmann M, Krentz D, Zwicklbauer K, Dorsch R, Wess G, Fischer A, Matiasek K, Hönl A, Fiedler S, Kolberg L, Hofmann-Lehmann R, Meli ML, Spiri AM, Helfer-Hungerbuehler AK, Felten S, Zablotski Y, Alberer M, Both UV, Hartmann K. Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study. Viruses. 2024 Jul 16;16(7):1144. doi: 10.3390/v16071144. PMID: 39066306; PMCID: PMC11281457.
The discovery of GS-441524 as an effective antiviral drug for cats with feline infectious peritonitis (FIP) has enabled feline patients to survive this once incurable, fatal disease. In the UK and Australia, GS-411524 is already legally available, while in the US the drug has only recently been available through selected compounding pharmacies. An 84-day treatment cycle has been shown to be successful in various clinical studies and has become an unofficial standard protocol. From a practical point of view, the daily administration of the drug for 12 weeks, as well as the cost of such treatment, can make it difficult or even impossible for cat owners to complete the entire prescribed treatment.
The aim of the researchers in Germany and Switzerland was to evaluate whether a 42-day treatment with GS-441524 is as effective as the currently recommended 84-day protocol. In a prospective randomized controlled treatment study, 40 cats were randomized to receive 15 mg/kg GS-441524 orally once daily for 42 or 84 days. Patients were diagnosed with FIP based on either FCoV RNA detected by RT-qPCR or RT-PCR in effusion in at least one body cavity with altered laboratory parameters typical of FIP. In addition to the diagnosis of FIP, other inclusion criteria included the presence of abdominal and/or pleural effusion, negative FeLV and FIV status, a body weight of at least 2 kg, and the absence of other serious diseases. The age of the cats ranged from 5.1 to 116.3 months, with 17 of the 40 cats being less than 1 year old. Breed distribution was as follows: 40 % Domestic Shorthairs (DSH), 20 % British Shorthairs (BSH) and 40 % other breeds. At the start of the study, 63 % cats had abdominal effusion, 12 % pleural effusion, and 25 % effusion in both cavities.
Each patient was treated for the first 7 days at the Center for Clinical Veterinary Medicine at the LMU in Munich. Treatment groups were blinded until day 7 of the study. The cats remained in their owners' homes for the remaining days of the study and returned every 2 weeks for follow-up examinations and diagnostic tests at the clinic. Tests included abdominal and thoracic ultrasonography, blood chemistry, hematology, urinalysis, measurement of viral RNA in effusion, blood, and feces, and anti-FCoV antibodies. Detailed cardiological and neurological examinations were performed at study entry. The final re-examination was performed 168 days after the start of treatment.
GS-441524 was supplied as 50mg tablets and was legally imported from the UK. Owners kept diaries documenting items such as activity, stool consistency, food intake and body weight. 19 cats (of 20) in each treatment group completed treatment. Two cats were euthanized during treatment (days 3 and 31) due to secondary complications.
Clinical remission was observed between days 14 and 84 with a median of 28 days, and within the first 42 days 37/40 cats went into complete clinical remission. Every cat that completed treatment showed significant improvement in hematological and clinical chemistry parameters. At the beginning of the study, viral RNA was detected in the blood of 35/40 cats, and by day 28 no more viremia was noted in any cat. During the second phase (days 42 to 84) of the study, in which only the long-term treatment group received the drugs, no significant differences were found in viral load in blood, effusion and feces or anti-FCOV antibodies. By 168 days, all 38 cats remaining in the study were in complete remission. Two cats with neurological or ocular signs also fully recovered during treatment.
The most frequently observed adverse events were diarrhea in 25/40 cats (20 % of which were diagnosed as severe based on stool evaluation), elevation of liver enzymes (mild to moderate) in 24/40 cats between days 1 and 84, lymphocytosis in 27/40 cats and a slight increase in SDMA above the reference interval in 25/40 cats. None of the patients experienced adverse effects related to the administration of GS-441524.
This study demonstrated that a shorter treatment of 42 days with oral GS-441524 was as effective as the currently recommended 84-day treatment. GS-441524 was generally well tolerated, with no significant adverse reactions noted. Limitations include that all patients received continuous professional veterinary care during the first 7 days of treatment, which is not common in most clinical practice. In addition, only patients with wet FIP were included and only the oral form of GS-441524 was used. The preparation used in the study was legally manufactured in a strictly controlled manner by BOVA Specials in London, UK. Many cat owners around the world still purchase oral and/or injectable GS-441524 from "black market" sources, so it is unknown whether the 42-day treatment is equally effective in these patients. -BJP
More details:
Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg. 2019 Apr;21(4):271-281. doi: 10.1177/1098612X19825701. Epub 2019 Feb 13. PMID: 30755068; PMCID: PMC6435921.
Murphy BG, Perron M, Murakami E, Bauer K, Park Y, Eckstrand C, Liepnieks M, Pedersen NC. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet Microbiol. 2018 Jun; 219:226-233. doi: 10.1016/j.vetmic.2018.04.026. Epub 2018 Apr 22. PMID: 29778200; PMCID: PMC7117434.
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