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. 2024 Jul 16;16(7):1144.
doi: 10.3390/v16071144.

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

Anna-M Zuzzi-Krebitz  1 , Katharina Buchta  1 , Michèle Bergmann  1 , Daniela Krentz  1 , Katharina Zwicklbauer  1 , Roswitha Dorsch  1 , Gerhard Wess  1 , Andrea Fischer  1 , Kaspar Matiasek  2 , Anne Hönl  1   2 , Sonja Fiedler  2 , Laura Kolberg  3 , Regina Hofmann-Lehmann  4 , Marina L Meli  4 , Andrea M Spiri  4 , A Katrin Helfer-Hungerbuehler  4 , Sandra Felten  5 , Yury Zablotski  1 , Martin Alberer  3 , Ulrich von Both  3   6 , Katrin Hartmann  1
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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

Anna-M Zuzzi-Krebitz et al. Viruses. .

Abstract

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Keywords: BOVA; FCoV; FIP; GS-441524; antiviral chemotherapy; feline coronavirus; therapy; treatment duration.

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Conflict of interest statement

The authors declare that they have no conflict of interest. The GS-441524 tablets were provided by BOVA Specials, London, UK, but BOVA played no role in the interpretation of study data or the decision to submit the manuscript for publication. No commercial conflict of interest exists as the information is solely for scientific dissemination.

Figures

Figure 1
Figure 1
Flow diagram illustrating enrollment, inclusion, process of randomized allocation to long and short treatment group, and outcome of cats in the study.
Figure 2
Figure 2
Timeline visualizing the in-hospital and on-site follow-up examinations throughout the study course. formula image: start of treatment with GS-441524; formula image: end of treatment of 20/40 cats on day 42; formula image: end of treatment of 20/40 cats on day 84; formula image: evaluation of laboratory parameters; formula image: measurement of virology parameters (including viral loads in blood, effusion and feces, anti-FCoV antibodies); formula image: abdominal ultrasonography; formula image: cardiologic examination; formula image: neurologic examination.
Figure 3
Figure 3
Timeline visualizing improvement of clinical parameters throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. Figures show average predictive values and 95% confidence intervals of each parameter. Grey shading marks the reference interval of the parameters. (A) Karnofsky’s score modified for cats. (B) Body weight. (C) Body temperature. (D) Volume of effusion subjectively evaluated during abdominal/thoracic ultrasonography and paracentesis (grades 0 (no effusion) to 3 (massive effusion)).
Figure 4
Figure 4
Timeline visualizing improvement of laboratory parameters throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. Figures show average predictive values and 95% confidence intervals of each parameter. Grey shading marks the reference interval of the parameters. Red asterisks mark significant differences (p < 0.05) of the parameters in the group comparison. (A) Hematocrit. (B) Lymphocyte count. (C) Eosinophil count. (D) Bilirubin concentration. (E) Total protein concentration. (F) Albumin concentration. (G) Globulin concentration. (H) Albumin/globulin ratio. (I) Serum amyloid A (SAA) concentration. (J) Alpha-1-acid-glycoprotein (AGP) concentration.
Figure 4
Figure 4
Timeline visualizing improvement of laboratory parameters throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. Figures show average predictive values and 95% confidence intervals of each parameter. Grey shading marks the reference interval of the parameters. Red asterisks mark significant differences (p < 0.05) of the parameters in the group comparison. (A) Hematocrit. (B) Lymphocyte count. (C) Eosinophil count. (D) Bilirubin concentration. (E) Total protein concentration. (F) Albumin concentration. (G) Globulin concentration. (H) Albumin/globulin ratio. (I) Serum amyloid A (SAA) concentration. (J) Alpha-1-acid-glycoprotein (AGP) concentration.
Figure 5
Figure 5
Heatmaps visualizing improvement of serum amyloid A (SAA) and alpha-1-acid-glycoprotein (AGP) concentrations throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. (A) SAA concentration. (B) AGP concentration. * Samples missing, e.g., due to severe anemia.
Figure 5
Figure 5
Heatmaps visualizing improvement of serum amyloid A (SAA) and alpha-1-acid-glycoprotein (AGP) concentrations throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. (A) SAA concentration. (B) AGP concentration. * Samples missing, e.g., due to severe anemia.
Figure 6
Figure 6
Feline coronavirus (FCoV) viral RNA loads in blood, effusion, and fecal samples and serum anti-FCoV antibody titers throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. (A) FCoV RNA loads in EDTA anticoagulated blood. (B) FCoV RNA loads in effusions. (C) FCoV RNA loads in feces. (D) Serum anti-FCoV antibody titers. FCoV RNA loads were determined by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Antibody titers were determined by indirect immunofluorescence assay (IFA). * Samples missing, e.g., due to severe anemia.
Figure 6
Figure 6
Feline coronavirus (FCoV) viral RNA loads in blood, effusion, and fecal samples and serum anti-FCoV antibody titers throughout the study course in both groups until day 84 of the study (comparison of treatment duration six versus twelve weeks). The red stop sign marks the end of treatment of the short treatment group; the blue stop sign marks the end of treatment of the long treatment group. (A) FCoV RNA loads in EDTA anticoagulated blood. (B) FCoV RNA loads in effusions. (C) FCoV RNA loads in feces. (D) Serum anti-FCoV antibody titers. FCoV RNA loads were determined by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Antibody titers were determined by indirect immunofluorescence assay (IFA). * Samples missing, e.g., due to severe anemia.
Figure 7
Figure 7
Histopathological characteristics of cat 21. (A) Spleen with capsular fibrosis (CF) on top of lymphoplasmacytic infiltrates (arrowhead) consistent with chronic perisplenitis. Occasional lymph follicles (white asterisk) and congestion are seen (arrows). (B) The liver likewise presented with an extensive capsular fibrosis (CF). There was a significant centrolobular degeneration suggestive of hypoxic changes (asterisk). (C) The brain showed multifocal spongiosis within cerebral cortex (asterisk) if compared to well-delineated unaffected segments (arrows). This change was compatible with malperfusive changes. Scale bars: (A) 235 µm; (B,C) 350 µm. (A–C): HE-FFPE.
Figure 8
Figure 8
Pathological findings in cat 14. (A) Lateral aspect of the right lung and pericardium (*). The lung presented with diffuse, marked dark-red discoloration and diffuse congestion. The apex lobe was focally attached to the pericardium. Scale bar = 1 cm. (B) Lung histology. There was a diffuse loss of lung architecture with diffuse and marked interstitial fibrosis, compression of bronchioles, and a mixed-cellular, predominantly mononuclear round cell infiltration. Lung, HE-FFPE. Scale bar = 100 µm. (C) Lung histology. Masson’s trichrome demonstrates the diffuse and marked interstitial fibrosis. Lung, MT-FFPE. Scale bar = 100 µm.
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