Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis

Pedersen, Niels C; Perron, Michel; Bannasch, Michael; Montgomery, Elizabeth; Murakami, Eisuke; Liepnieks, Molly; Liu, Hongwei

This study was conducted under protocols 19336 and 19863 approved by the Institutional Animal Care and Use Committee and the Clinical Trial Review Board of the Veterinary Medical Teaching Hospital (VMTH) Clinical Trials Committee, University of California (UC), Davis. Institutional rules precluded the use of diseased cats obtained directly from shelters or kitten foster/rescue groups, thus requiring that all cats be legally owned/adopted and treated under specific conditions and with owner consent (supplementary material). The study did not incorporate a control group because there is no effective treatment to compare it against. A placebo treatment group was not included, given that preparatory in vitro and in vivo studies indicated that GS-441524 would be safe and more effective than no treatment. 12 Case selection and disease confirmation Cats with FIP were recruited from owners or their veterinarians seeking current treatment options or access to an earlier antiviral drug trial. 6 The initial diagnosis of FIP was based primarily on characteristic signalment, clinical histories and disease signs, routine laboratory test results, and examination of abdominal or thoracic effusions. A more definitive diagnosis based on RT-PCR or immunohistochemistry was desirable but not essential for inclusion. Cats with obvious ocular or neurological disease were discouraged to enter the trial because of concerns over the ability of antiviral drugs, including GS-441524, to penetrate the blood-brain or blood-eye barriers. 12, 15 Thirty-one cats and their owners were ultimately recruited (Table 1) . Owners or representatives of 26 cats came to UC Davis for initial treatment, and five owners and their cats (CT59, CT73, CT76, CT78, CT80) were treated by their local veterinarian. Cats seen at UC Davis were re-evaluated and their FIP diagnosis reconfirmed based on signalment, clinical history, physical examination, prior laboratory test results and a repeat of complete blood count (CBC), serum protein and effusion analyses. Thoracic or abdominal effusions from cats with wet FIP were confirmed positive for FIPV 7b RNA by RT-PCR. 16 Cats with signs of non-effusive FIP were further tested by abdominal and thoracic ultrasonography for primary lesions. Ocular disease was confirmed by the ophthalmology service of the VMTH, UC Davis. Neurological status in cases with possible central nervous system disease signs was evaluated by the VMTH neurology service.