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 treatment for cats with feline infectious peritonitis (FIP) has allowed feline patients to survive this once untreatable fatal condition. In the UK and Australia, compounded GS-411524 has been legally available, while the medication has more recently become available in the U.S through select compounding pharmacies. An 84-day treatment cycle has shown success in various clinical trials and has become the unofficial standard protocol. From a practical standpoint, daily medicating for 12 weeks as well as the cost of such treatment can make it difficult or even impossible for cat owners to complete an entire prescribed course.
Investigators in Germany and Switzerland aimed to evaluate whether a 42-day treatment of GS-441524 was as effective as the currently recommended 84-aday protocol. In a prospective randomized controlled treatment study, 40 cats were enrolled and randomized to receive either 15 mg/kg GS-441524 orally once daily for either 42 or 84 days. Patients were diagnosed with FIP by either FCoV RNA detected by RT-qPCR or RT-PCR in effusion in at least one body cavity with altered laboratory parameters typical for FIP. In addition to FIP diagnosis, other inclusion criteria included the presence of abdominal and/or pleural effusion, negative FeLV and FIV status, body weight of at least 2 kg, and absence of other severe diseases. Cats ranged in age from 5.1 to 116.3 months, with 17 out of 40 under 1 year of age. The breed distribution was the following: 40% domestic short hair (DSH), 20% British short hair (BSH), and 40% other breeds. At the start of the study, 63% of cats had abdominal effusion, 12% pleural effusion and 25% effusion of both cavities.
Each patient was treated in-house at the Centre for Clinical Veterinary Medicine at LMU Munich for the first 7 days. The treatment groups were blinded until day 7 of the study. Cats remained in their owner’s homes for the remainder of the study days and returned every 2 weeks for on-site follow-up examinations and diagnostic tests. Tests included abdominal and thoracic ultrasonography, blood chemistry, hematology, urinalysis, viral RNA load measurements in effusion, blood, and feces, and anti-FCoV antibodies. Detailed cardiologic and neurologic examinations were performed upon entry to the study. A final recheck was performed 168 days after the start of treatment.
The compounded GS-441524 was provided as 50 mg tablets and were legally imported from the UK. Owners maintained daily diaries to document items such as activity, fecal consistency, food intake, and body weight. 19 cats (out of 20) in each treatment allocation completed their courses of treatment. 2 cats were euthanized during treatment (day 3 and day 31) due to secondary complications.
Clinical remission was noted between days 14 to 84 with a median of 28 days, and by the first 42 days, 37/40 cats went into complete clinical remission. Each cat who completed treatment
had significant improvement in hematologic and clinical chemistry parameters. Viral RNA was detected in the blood of 35/40 cats at the start of the study, and by day 28, viremia was no longer noted in any cat. During the second phase (days 42 to 84) of the study where only the long treatment group received medication, there were no significant differences regarding viral loads in blood, effusion, and feces or anti-FCOV antibodies. By 168 days, all 38 cats that remained in the study remained in complete remission. Two cats with neurologic or ocular signs also completely resolved during treatment.
The most common adverse events observed included diarrhea in 25/40 cats (20% of those diagnosed as severe based on fecal score), increase in liver enzyme activity (mild to moderate) in 24/40 cats between days 1 and 84, lymphocytosis in 27/40 cats, and a mild increase in SDMA above reference interval in 25/40 cats. None of the patients succumbed to adverse events related to GS-441524 administration.
This study demonstrated that a shorter treatment of duration of 42 days with oral GS-441524 was as effective as the current 84-day recommendation. GS-441524 was generally well tolerated, with no significant adverse events noted. Limitations include all patients receiving around the clock professional veterinary care for the first 7 days of treatment which is not common in most clinical practices. Additionally, only patients with wet FIP were included and only the oral formulation of GS-441524 was used. The product 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 if a 42-day course is just as effective in those patients. -BJP
For further reading:
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.