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

Abstract

Objectives: The aim of this study was to determine the safety and efficacy of the nucleoside analog GS-441524 for cats suffering from various forms of naturally acquired feline infectious peritonitis (FIP).

Methods: Cats ranged from 3.4-73 months of age (mean 13.6 months); 26 had effusive or dry-to-effusive FIP and five had non-effusive disease. Cats with severe neurological and ocular FIP were not recruited. The group was started on GS-441524 at a dosage of 2.0 mg/kg SC q24h for at least 12 weeks and increased when indicated to 4.0 mg/kg SC q24h.

Results: Four of the 31 cats that presented with severe disease died or were euthanized within 2-5 days and a fifth cat after 26 days. The 26 remaining cats completed the planned 12 weeks or more of treatment. Eighteen of these 26 cats remain healthy at the time of publication (OnlineFirst, February 2019) after one round of treatment, while eight others suffered disease relapses within 3-84 days. Six of the relapses were non-neurological and two neurological. Three of the eight relapsing cats were treated again at the same dosage, while five cats had the dosage increased from 2.0 to 4.0 mg/kg q24h. The five cats treated a second time at the higher dosage, including one with neurological disease, responded well and also remain healthy at the time of publication. However, one of the three cats re-treated at the original lower dosage relapsed with neurological disease and was euthanized, while the two remaining cats responded favorably but relapsed a second time. These two cats were successfully treated a third time at the higher dosage, producing 25 long-time survivors. One of the 25 successfully treated cats was subsequently euthanized due to presumably unrelated heart disease, while 24 remain healthy.

Conclusions and relevance: GS-441524 was shown to be a safe and effective treatment for FIP. The optimum dosage was found to be 4.0 mg/kg SC q24h for at least 12 weeks.

Keywords: FIP; GS-441524; Nucleoside analog; feline infectious peritonitis; field trial.

Figure 1

Time scale for the treatment and clinical outcome of 31 cats that were enrolled in the GS-441524 field trial. The period of treatment is indicated by a solid line (2 mg/kg dose) or a broken line (4 mg/kg dose). Asterisks indicate the point of relapse. The treatment end date for the cats that achieved a sustained clinical remission is given in parenthesis. The time point and cause of death is indicated by a cross

Figure 2

Mean (solid line) and 1 SD (dashes) of body temperatures for the first 5 days of GS-441524 treatment. The normal temperature range for cats is 100–102.5°F (37.7–39.1°C). Temperatures dropped into normal range within 12–36 h of starting treatment

Figure 3

(a) Mean white blood cell count with standard error for 26 cats that completed the primary treatment regimen of 12 or more weeks. (b) Mean absolute blood lymphocyte count with standard error for 26 cats that completed at least 12 weeks of treatment

Figure 4

Mean packed cell volume (PCV) with standard error for 26 cats that completed at least 12 weeks of treatment. The dotted line indicates the trend of rising PCV over time

Figure 5

Mean serum total protein levels and standard error for 26 cats that completed at least 12 weeks of treatment

Figure 6

(a) Mean serum globulin levels and standard error for 26 cats that completed at least 12 weeks of treatment. (b) Mean serum albumin levels and standard error for 26 cats that completed at least 12 weeks of treatment

Figure 7

Mean albumin:globulin (A/G) ratios and standard error for 26 cats that completed at least 12 weeks of treatment

Figure 8

Cross-section through the heart of cat CT80 showing extreme hypertrophy of the left ventricular wall and septum and extreme narrowing of the chamber