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
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Compound
2.3. Inclusion Criteria and Study Cohort
2.4. Monitoring of Clinical and Laboratory Parameters
2.5. Monitoring of FCoV Viral Loads and Anti-FCoV Antibodies
2.6. Data Analysis
3. Results
3.1. Cats at Inclusion
3.2. Efficacy of the Oral GS-441524
3.3. Comparison between Short and Long Treatment
3.4. Adverse Events during Oral GS-441524 Treatment in Cats with FIP
3.5. Postmortem Findings in Cats 21 and 14
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Pedersen, N.C. Virologic and immunologic aspects of feline infectious peritonitis virus infection. In Coronaviruses; Lai, M.M.C., Stohlman, S.A., Eds.; Springer: Boston, MA, USA, 1987; pp. 529–550. [Google Scholar]
- Murphy, B.G.; Perron, M.; Murakami, E.; Bauer, K.; Park, Y.; Eckstrand, C.; Liepnieks, M.; Pedersen, N.C. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet. Microbiol. 2018, 219, 226–233. [Google Scholar] [CrossRef] [PubMed]
- Pedersen, N.C.; 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, 21, 271–281. [Google Scholar] [CrossRef] [PubMed]
- Addie, D.D.; Covell-Ritchie, J.; Jarrett, O.; Fosbery, M. Rapid resolution of non-effusive feline infectious peritonitis uveitis with an oral adenosine nucleoside analogue and feline interferon omega. Viruses 2020, 12, 1216. [Google Scholar] [CrossRef] [PubMed]
- Dickinson, P.J.; Bannasch, M.; Thomasy, S.M.; Murthy, V.D.; Vernau, K.M.; Liepnieks, M.; Montgomery, E.; Knickelbein, K.E.; Murphy, B.; Pedersen, N.C. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. J. Vet. Intern. Med. 2020, 34, 1587–1593. [Google Scholar] [CrossRef] [PubMed]
- Jones, S.; Novicoff, W.; Nadeau, J.; Evans, S. Unlicensed GS-441524-like antiviral therapy can be effective for at-home treatment of feline infectious peritonitis. Animals 2021, 11, 2257. [Google Scholar] [CrossRef] [PubMed]
- Katayama, M.; Uemura, Y. Therapeutic effects of Mutian® xraphconn on 141 client-owned cats with feline infectious peritonitis predicted by total bilirubin levels. Vet. Sci. 2021, 8, 328. [Google Scholar] [CrossRef] [PubMed]
- Krentz, D.; Zenger, K.; Alberer, M.; Felten, S.; Bergmann, M.; Dorsch, R.; Matiasek, K.; Kolberg, L.; Hofmann-Lehmann, R.; Meli, M.L.; et al. Curing cats with feline infectious peritonitis with an oral multi-component drug containing GS-441524. Viruses 2021, 13, 2228. [Google Scholar] [CrossRef] [PubMed]
- Addie, D.D.; Silveira, C.; Aston, C.; Brauckmann, P.; Covell-Ritchie, J.; Felstead, C.; Fosbery, M.; Gibbins, C.; Macaulay, K.; McMurrough, J.; et al. Alpha-1 acid glycoprotein reduction differentiated recovery from remission in a small cohort of cats treated for feline infectious peritonitis. Viruses 2022, 14, 744. [Google Scholar] [CrossRef] [PubMed]
- Coggins, S.J.; Norris, J.M.; Malik, R.; Govendir, M.; Hall, E.J.; Kimble, B.; Thompson, M.F. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524. J. Vet. Intern. Med. 2023, 37, 1772–1783. [Google Scholar] [CrossRef]
- Green, J.; Syme, H.; Tayler, S. Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524. J. Vet. Intern. Med. 2023, 37, 1784–1793. [Google Scholar] [CrossRef]
- Taylor, S.S.; Coggins, S.; Barker, E.N.; Gunn-Moore, D.; Jeevaratnam, K.; Norris, J.M.; Hughes, D.; Stacey, E.; MacFarlane, L.; O’Brien, C.; et al. Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020–2022). J. Feline Med. Surg. 2023, 25, 1098612X231194460. [Google Scholar] [CrossRef] [PubMed]
- Cosaro, E.; Pires, J.; Castillo, D.; Murphy, B.G.; Reagan, K.L. Efficacy of oral remdesivir compared to GS-441524 for treatment of cats with naturally occurring effusive feline infectious peritonitis: A blinded, non-inferiority study. Viruses 2023, 15, 1680. [Google Scholar] [CrossRef] [PubMed]
- Yin, Y.; Li, T.; Wang, C.; Liu, X.; Ouyang, H.; Ji, W.; Liu, J.; Liao, X.; Li, J.; Hu, C. A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China. Sci. Rep. 2021, 11, 5208. [Google Scholar] [CrossRef] [PubMed]
- Lv, J.; Bai, Y.; Wang, Y.; Yang, L.; Jin, Y.; Dong, J. Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis. Front. Vet. Sci. 2022, 9, 1002488. [Google Scholar] [CrossRef] [PubMed]
- Krentz, D.; Zwicklbauer, K.; Felten, S.; Bergmann, M.; Dorsch, R.; Hofmann-Lehmann, R.; Meli, M.L.; Spiri, A.M.; von Both, U.; Alberer, M.; et al. Clinical follow-up and postmortem findings in a cat that was cured of feline infectious peritonitis with an oral antiviral drug containing GS-441524. Viruses 2022, 14, 2040. [Google Scholar] [CrossRef]
- Zwicklbauer, K.; Krentz, D.; Bergmann, M.; Felten, S.; Dorsch, R.; Fischer, A.; Hofmann-Lehmann, R.; Meli, M.L.; Spiri, A.M.; Alberer, M.; et al. Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524. J. Feline Med. Surg. 2023, 25, 1098612X231183250. [Google Scholar] [CrossRef] [PubMed]
- Meli, M.L.; Spiri, A.M.; Zwicklbauer, K.; Krentz, D.; Felten, S.; Bergmann, M.; Dorsch, R.; Matiasek, K.; Alberer, M.; Kolberg, L.; et al. Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524. Viruses 2022, 14, 1069. [Google Scholar] [CrossRef] [PubMed]
- Murphy, B.G.; Castillo, D.; Neely, N.E.; Kol, A.; Brostoff, T.; Grant, C.K.; Reagan, K.L. Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials. Viruses 2024, 16, 462. [Google Scholar] [CrossRef]
- Freeman, L.; Becvarova, I.; Cave, N.; MacKay, C.; Nguyen, P.; Rama, B.; Takashima, G.; Tiffin, R.; Van Beukelen, P.; Yathiraj, S. WSAVA nutritional assessment guidelines. J. Feline Med. Surg. 2011, 13, 516–525. [Google Scholar] [CrossRef]
- Thayer, V.; Gogolski, S.; Felten, S.; Hartmann, K.; Kennedy, M.; Olah, G.A. 2022 AAFP/Every cat feline infectious peritonitis diagnosis guidelines. J. Feline Med. Surg. 2022, 24, 905–933. [Google Scholar] [CrossRef]
- Tasker, S.; Addie, D.D.; Egberink, H.; Hofmann-Lehmann, R.; Hosie, M.J.; Truyen, U.; Belak, S.; Boucraut-Baralon, C.; Frymus, T.; Lloret, A.; et al. Feline infectious peritonitis: European advisory board on cat diseases guidelines. Viruses 2023, 15, 1847. [Google Scholar] [CrossRef] [PubMed]
- Hartmann, K. Feline infectious peritonitis. Vet. Clin. N. Am. Small Anim. Pract. 2005, 35, 39–79. [Google Scholar] [CrossRef] [PubMed]
- Dülsner, A.; Hack, R.; Krüger, C.; Pils, M.; Scherer, K.; Schmelting, B.; Schmidt, M.; Weinert, H.; Jordan, T. Fachinformation aus dem Ausschuss für Tier-Schutzbeauftragte und dem Arbeitskreis 4 in der TVT; Empfehlung zur Blutentnahme bei Versuchstieren, Insbesondere Kleinen Versuchstieren. Available online: https://www.gv-solas.de/wp-content/uploads/2017/07/Empfehlung-zur-Blutentnahme_2017-1.pdf (accessed on 5 September 2022).
- Hartmann, K.; Kuffer, M. Karnofsky’s score modified for cats. Eur. J. Med. Res. 1998, 3, 95–98. [Google Scholar] [PubMed]
- Hansen, A.E.; Schaap, M.K.; Kjelgaard-Hansen, M. Evaluation of a commercially available human serum amyloid A (SAA) turbidimetric immunoassay for determination of feline SAA concentration. Vet. Res. Commun. 2006, 30, 863–872. [Google Scholar] [CrossRef] [PubMed]
- Helfer-Hungerbuehler, A.K.; Spiri, A.M.; Meili, T.; Riond, B.; Krentz, D.; Zwicklbauer, K.; Buchta, K.; Zuzzi-Krebitz, A.-M.; Hartmann, K.; Hofmann-Lehmann, R.; et al. Alpha-1-acid glycoprotein quantification via spatial proximity analyte reagent capture luminescence assay: Application as diagnostic and prognostic marker in serum and effusions of cats with feline infectious peritonitis undergoing GS-441524 therapy. Viruses 2024, 16, 791. [Google Scholar] [CrossRef] [PubMed]
- Purina Fecal Scoring Chart. Available online: https://www.purinainstitute.com/centresquare/nutritional-and-clinical-assessment/purina-fecal-scoring-chart (accessed on 5 September 2022).
- Meli, M.; Kipar, A.; Muller, C.; Jenal, K.; Gonczi, E.; Borel, N.; Gunn-Moore, D.; Chalmers, S.; Lin, F.; Reinacher, M.; et al. High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and in naturally FCoV-infected cats. J. Feline Med. Surg. 2004, 6, 69–81. [Google Scholar] [CrossRef] [PubMed]
- Gut, M.; Leutenegger, C.M.; Huder, J.B.; Pedersen, N.C.; Lutz, H. One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses. J. Virol. Methods 1999, 77, 37–46. [Google Scholar] [CrossRef] [PubMed]
- Lutz, H.; Hauser, B.; Horzinek, M.C. Feline infectious peritonitis. Tijdschr. Diergeneeskd. 1985, 110, 939–946. [Google Scholar] [PubMed]
- Osterhaus, A.D.; Horzinek, M.C.; Reynolds, D.J. Seroepidemiology of feline infectious peritonitis virus infections using transmissible gastroenteritis virus as antigen. Zentralblatt Veterinärmedizin Reihe B 1977, 24, 835–841. [Google Scholar] [CrossRef]
- Brunner, C.; Kanellos, T.; Meli, M.L.; Sutton, D.J.; Gisler, R.; Gomes-Keller, M.A.; Hofmann-Lehmann, R.; Lutz, H. Antibody induction after combined application of an adjuvanted recombinant FeLV vaccine and a multivalent modified live virus vaccine with a chlamydial component. Vaccine 2006, 24, 1838–1846. [Google Scholar] [CrossRef]
- Felten, S.; Klein-Richers, U.; Hofmann-Lehmann, R.; Bergmann, M.; Unterer, S.; Leutenegger, C.M.; Hartmann, K. Correlation of feline coronavirus shedding in feces with coronavirus antibody titer. Pathogens 2020, 9, 598. [Google Scholar] [CrossRef] [PubMed]
- Mateos González, M.; Sierra Gonzalo, E.; Casado Lopez, I.; Arnalich Fernández, F.; Beato Pérez, J.L.; Monge Monge, D.; Vargas Núñez, J.A.; García Fenoll, R.; Suárez Fernández, C.; Freire Castro, S.J.; et al. The prognostic value of eosinophil recovery in COVID-19: A multicentre, retrospective cohort study on patients hospitalised in spanish hospitals. J. Clin. Med. 2021, 10, 305. [Google Scholar] [CrossRef] [PubMed]
- Kroegel, C.; Schreiber, J. Der eosinophile Granulozyt—vom Ursprung bis zur therapeutischen Zielzelle. Z. Pneumol. 2018, 15, 297–298. [Google Scholar] [CrossRef]
- Fraissé, M.; Logre, E.; Mentec, H.; Cally, R.; Plantefève, G.; Contou, D. Eosinophilia in critically ill COVID-19 patients: A French monocenter retrospective study. Crit. Care 2020, 24, 635. [Google Scholar] [CrossRef] [PubMed]
- Kipar, A.; Meli, M.L.; Baptiste, K.E.; Bowker, L.J.; Lutz, H. Sites of feline coronavirus persistence in healthy cats. J. Gen. Virol. 2010, 91, 1698–1707. [Google Scholar] [CrossRef] [PubMed]
- Mustaffa-Kamal, F.; Liu, H.; Pedersen, N.C.; Sparger, E.E. Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV). BMC Vet. Res. 2019, 15, 165. [Google Scholar] [CrossRef] [PubMed]
- Pedersen, N.C.; Kim, Y.; Liu, H.; Galasiti Kankanamalage, A.C.; Eckstrand, C.; Groutas, W.C.; Bannasch, M.; Meadows, J.M.; Chang, K.O. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J. Feline Med. Surg. 2018, 20, 378–392. [Google Scholar] [CrossRef] [PubMed]
- Slaviero, M.; Cony, F.G.; da Silva, R.C.; De Lorenzo, C.; de Almeida, B.A.; Bertolini, M.; Driemeier, D.; Pavarini, S.P.; Sonne, L. Pathological findings and patterns of feline infectious peritonitis in the respiratory tract of cats. J. Comp. Pathol. 2024, 210, 15–24. [Google Scholar] [CrossRef]
- Kent, A.M.; Guan, S.; Jacque, N.; Novicoff, W.; Evans, S.J.M. Unlicensed antiviral products used for the at-home treatment of feline infectious peritonitis contain GS-441524 at significantly different amounts than advertised. J. Am. Vet. Med. Assoc. 2024, 262, 489–497. [Google Scholar] [CrossRef]
Day | Physical Examination # | Abdominal and Thoracic Ultrasonography # | Detailed Cardiologic and Neurologic Examinations # | Hematology #, Clinical Chemistry #, Including SDMA 1, SAA 2, AGP 3, and Urinalysis * | Viral RNA Loads (RT-qPCR) in Effusion, Blood, and Feces | Anti-FCoV Antibodies |
---|---|---|---|---|---|---|
1 | x | x | x | x | x | x |
3 | x | x | x | |||
5 | x | x | x | x | ||
7 | x | x | x | x | ||
14 | x | x | x | x | ||
28 | x | x | x | x | ||
42 | x | x | x | x | x | x |
56 | x | x | x | x | ||
84 | x | x | x | x | x | x |
Total Number of Cats | Cats with 42 Days of Treatment | Cats with 84 Days of Treatment | p-Value * | ||
---|---|---|---|---|---|
Number of Cats | 40 | 20 | 20 | ||
Breed | DSH 1 | 16 | 11 | 5 | 0.13 |
BSH 2 | 8 | 3 | 5 | 0.48 | |
other breeds 3 | 16 | 6 | 10 | 0.32 | |
Age | <1 year | 17 | 10 | 7 | 0.81 |
>1 year | 23 | 11 | 12 | 0.83 | |
Sex | female intact | 7 | 5 | 2 | 0.26 |
female neutered | 2 | 1 | 1 | 1.00 | |
male intact | 11 | 3 | 8 | 0.13 | |
male neutered | 20 | 11 | 9 | 0.65 | |
Location of Effusion | abdominal | 25 | 14 | 11 | 0.55 |
pleural | 5 | 3 | 2 | 0.65 | |
abdominal/pleural | 10 | 3 | 7 | 0.21 |
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Zuzzi-Krebitz, A.-M.; Buchta, K.; Bergmann, M.; Krentz, D.; Zwicklbauer, K.; Dorsch, R.; Wess, G.; Fischer, A.; Matiasek, K.; Hönl, A.; et al. 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, 16, 1144. https://doi.org/10.3390/v16071144
Zuzzi-Krebitz A-M, Buchta K, Bergmann M, Krentz D, Zwicklbauer K, Dorsch R, Wess G, Fischer A, Matiasek K, Hönl A, et al. 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; 16(7):1144. https://doi.org/10.3390/v16071144
Chicago/Turabian StyleZuzzi-Krebitz, Anna-M., Katharina Buchta, Michèle Bergmann, Daniela Krentz, Katharina Zwicklbauer, Roswitha Dorsch, Gerhard Wess, Andrea Fischer, Kaspar Matiasek, Anne Hönl, and et al. 2024. "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 16, no. 7: 1144. https://doi.org/10.3390/v16071144