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Abstract

Objectives

Feline infectious peritonitis (FIP) can be treated with antiviral agents such as remdesivir and GS-441524, with a commonly used treatment duration of 12 weeks. Although serum amyloid A (SAA) and alpha-1 acid glycoprotein (α1AG) have been proposed as markers of disease improvement, the criteria for treatment cessation before this duration remain unclear. This study evaluated whether SAA and α1AG could guide treatment cessation in cats with FIP and whether a high-dose induction protocol could allow treatment duration to be shortened.

Methods

A total of 30 cats with FIP, excluding those presenting solely with neurological signs, received high-dose (⩾20 mg/kg) therapy using injectable remdesivir followed by oral GS-441524 or oral GS-441524 alone. Remdesivir was administered once daily, whereas GS-441524 was given as the total daily dose divided into two doses 12 h apart. After initial improvement, the dose was reduced to the maintenance dose of 12–15 mg/kg based on clinical signs. Clinical signs, SAA and α1AG were monitored. Treatment was discontinued when clinical signs resolved and both SAA below 6 mg/l and α1AG 0.5 g/l or below were maintained for at least 2 consecutive weeks before 12 weeks or at 12 weeks regardless of these criteria.

Results

Of the 30 cats, 29 (96.7%) survived. Among these, 22 (75.9%) met the treatment termination criteria within 12 weeks (median treatment duration 54 days [range 41–71]), whereas seven completed 12 weeks. No relapse was observed during treatment or within the 3-month follow-up period.

Conclusions and relevance

Although high-dose induction therapy is not a standard protocol, no clear adverse effects were observed, and treatment could be discontinued before 12 weeks in some cats. In cats with shortened treatment duration, improvement in SAA and α1AG concentrations appeared to be useful indicators for guiding treatment cessation. Further studies are required to clarify the clinical benefit of high-dose induction therapy.

Plain language summary

Defining treatment protocols and termination criteria for safely and rapidly completing treatment of feline infectious peritonitis with remdesivir and GS-441524

Feline infectious peritonitis (FIP) is a serious viral disease in cats that can now be treated with antiviral drugs such as remdesivir and GS-441524. However, the ideal length of treatment is still debated, and many cats are treated for a fixed period of 12 weeks, even if they appear to improve earlier. Prolonged treatment can increase costs and stress for both cats and owners. In this study, we investigated whether treatment could be safely shortened by using a high-dose induction protocol, in which treatment is started at a higher dose and then reduced once the cat improves. We also examined whether blood markers of inflammation, serum amyloid A and alpha-1 acid glycoprotein, could help determine when it is safe to stop treatment. We treated 30 cats with FIP using remdesivir and/or GS-441524. Most cats received an initial high dose followed by a lower maintenance dose. Treatment was stopped early in many cats once their clinical signs resolved and their blood markers returned to normal. Importantly, no relapses were observed during the follow-up period. These results suggest that, in some cats, FIP treatment may be safely shortened using a high-dose induction approach combined with careful monitoring of clinical signs and specific blood markers. This strategy may reduce treatment duration and burden while maintaining safety, although further studies are needed to confirm these findings.

Keywords

Feline infectious peritonitis remdesivir GS-441524 treatment duration alpha-1-acid glycoprotein serum amyloid A

Introduction

Feline infectious peritonitis (FIP), a systemic inflammatory disease, arises when feline enteric coronavirus mutates into FIP virus (FIPV).^1
–3 Recently, antiviral agents, such as the nucleoside analogue remdesivir and GS-441524, have proven effective in FIP treatment.^4,5

GS-441524 inhibits FIPV replication in cultured cells, including Crandell–Rees feline kidney cells.^4,5 It has also been used in clinical cases of FIP and demonstrated favourable long-term outcomes.^6,7 Remdesivir is the prodrug of GS-441524.⁸ It was approved for the treatment of COVID-19.⁹ Previously, as GS-441524 was not approved, remdesivir was used as an alternative for treating FIP, with favourable clinical outcomes such as improvement of clinical signs of FIP.¹⁰ Subsequently, a veterinary compounding pharmacy in Australia (Bova Aus) enabled the first legal access to a veterinary formulation of remdesivir and later compounded GS-441524 for FIP treatment, making GS-441524 tablets available. Currently, a licensed formulation of GS-441524 tablets is available in many countries, including Sweden, Germany, Finland, Norway, South Africa, Japan, Cyprus, Singapore, Czech Republic, Ireland, Greece, Canada, The Netherlands, Portugal, Switzerland, Hong Kong and France. In the USA and Canada, the drugs are supplied from Bova under franchise to Stokes Pharmacy and Trutina, respectively. Combination protocols using both drugs have also been reported to produce favourable treatment outcomes after adjusting for dosage and other factors.^7,11,12

The treatment of FIP with GS-441524 was initially reported to require a 12-week course, taking into account the risk of relapse after therapy.⁶ Although subsequent dose escalation has been implemented in response to changes in formulation and to reduce relapse rates, a 12-week treatment period remains widely adopted.^11
–13 Both licensed remdesivir and GS-441524 are expensive, and a continuous 12-week course of treatment may represent a substantial financial burden for some owners, potentially influencing treatment decisions even in cases with a favourable prognosis.¹⁴

A study involving a large number of cats has reported clinical improvement with treatment durations of less than 12 weeks; however, treatment in that study was not intentionally discontinued according to a predefined shortened protocol.⁷ A predefined shortened protocol of 6 weeks has also been reported.¹⁵ In that study, treatment duration was assigned as either 6 or 12 weeks before initiation of therapy, and discontinuation was not based on individual case-by-case assessment. The high-dose induction protocol initiates treatment at a dosage typically used for neurological FIP (⩾20 mg/kg), regardless of clinical presentation, followed by a reduction to a maintenance dose of 12–15 mg/kg based on treatment response. Intravenous remdesivir was administered q24h, whereas oral GS-441524 was administered as the total daily dose divided into two doses given approximately 12 h apart. We previously reported that, after high-dose induction therapy consisting of either remdesivir followed by oral GS-441524 or oral GS-441524 alone, treatment with GS-441524 could be discontinued before 84 days if clinical signs had resolved and acute phase proteins (APP) and the albumin:globulin (A:G) ratio had improved to meet the criteria for treatment cessation.¹⁶ No relapse was observed when adjunctive mefloquine was administered after GS-441524 discontinuation. As no significant adverse events were reported, these findings suggest that a high-dose induction regimen may allow shortening of GS-441524 treatment without increasing the risk of adverse events or relapse. However, further investigation is required to determine the clinical utility of this approach. Furthermore, FIP confined to the nervous system may be associated with insufficient systemic cytokine release, potentially limiting the usefulness of APP for guiding treatment decisions.^17,18 Therefore, cats presenting exclusively with neurological signs were excluded from this study, and alternative APP-independent criteria for determining treatment cessation may be required for such cases.

In the previous report,¹⁶ some cases showed gradual improvement in the A:G ratio that did not return to baseline even after 84 days of treatment. Other studies have indicated that normalisation of the A:G ratio may be delayed in some cases.^12,19 The A:G ratio reflects composite changes in albumin recovery and globulin reduction and may therefore be influenced by factors beyond active FIP inflammation. Accordingly, although monitoring the A:G ratio is useful in assessing overall treatment progress, its suitability as a sole indicator for determining treatment termination may be limited. Furthermore, in that report, adjuvant mefloquine therapy was administered when GS-441524 treatment was completed within 84 days. However, the clinical efficacy of mefloquine against FIP remains unclear,²⁰ and its antiviral effect may be weaker than that of GS-441524 and remdesivir. Therefore, the necessity of adjunctive therapy with mefloquine should be critically evaluated.

In this study, we aimed to evaluate whether high-dose induction therapy with remdesivir and oral GS-441524 could be discontinued based on improvements in clinical signs, serum amyloid A (SAA) and alpha-1 acid glycoprotein (α1AG), and to evaluate whether terminating GS-441524 treatment before 12 weeks without adjunctive mefloquine would influence relapse rates.

Materials and methods

This study was conducted between January and August 2024 and included 30 cats diagnosed with FIP at Kobe Animal Clinic. All cats received high-dose induction therapy. In this study, high-dose induction therapy was defined by the authors as initiating treatment at 20 mg/kg/day with the aim of achieving adequate antiviral activity, including in the central nervous system, regardless of pretreatment clinical signs, followed by dose reduction to a maintenance dose based on the initial clinical signs of FIP. A comparison with the previously reported standard-dose protocol was not conducted because of concerns regarding survival rates and the risk of relapse. A commonly used standard treatment protocol for FIP consists of daily administration for 12 weeks at a dose determined according to clinical signs, with higher doses recommended particularly when ocular or neurological signs are present.^7,12,13 If clinical signs do not improve sufficiently, escalation of the dose and/or extension of the treatment period may be considered. Furthermore, as FIP confined to the nervous system may limit the utility of APP for guiding treatment decisions, cats presenting exclusively with neurological signs were excluded from this study.

Diagnosis

The definitive diagnosis of FIP was based on a comprehensive evaluation, including signalment, clinical signs, haematological findings, blood plasma biochemistry, imaging results, cytological examination of effusions and granulomatous lymph node lesions, feline coronavirus (FCoV) RT-qPCR on effusions or lymph node aspirates, as well as blood testing and immunohistochemistry. A definitive diagnosis was confirmed when histopatho-logical findings were consistent with FIP and immunohistochemical staining demonstrated FCoV antigen positivity. However, in cases where histopathological confirmation was not feasible, provisional diagnosis and classification were made based on positive FCoV RT-qPCR results. All cases were evaluated by veterinarians with extensive clinical experience following the European Advisory Board on Cat Diseases guidelines.²¹ If the signalment, medical history, clinical examination and clinicopathological findings strongly suggested FIP, and blood samples tested positive for FCoV by RT-qPCR, the case was considered highly suspicious for FIP, even without cytology or aqueous humour analysis. Although FCoV RT-PCR testing using whole blood has been reported to have low sensitivity and show potentially false-positive results,^22,23 a positive result was considered to further support a presumptive diagnosis of FIP when other clinical and laboratory findings suggested FIP and when RT-qPCR testing of other samples or histopathological examination was not feasible. In cases where histopathological confirmation was not feasible but FIP was strongly suspected based on comprehensive evaluation, antiviral therapy was initiated. When clinical signs and laboratory findings improved after treatment, these cases were retrospectively diagnosed as FIP. Based on clinical and laboratory findings, FIP was classified into two forms: effusive and non-effusive. Subsequently, each form was subcategorised according to the presence or absence of ocular or neurological involvement.

Treatment protocol

Treatment for FIP was administered using 50 mg tablets of GS-441524 (compounded by Bova Specials UK). In a subset of cats, therapy was initiated with intravenous remdesivir (Jubi-R; Jubilant Generics) and subsequently transitioned to oral GS-441524. If the cat’s clinical signs and general condition rendered oral administration unsuitable, treatment was initiated with intravenous remdesivir. If oral administration was feasible, treatment was initiated with oral GS-441524. The initial treatment dose for all cats was set at the minimum unit exceeding 20 mg/kg, irrespective of the clinical signs. GS-441524 tablets could be quartered, allowing dose adjustments in 12.5 mg increments. Remdesivir, supplied at a concentration of 5 mg/ml, was adjusted in 5 mg increments. Remdesivir was diluted and administered intravenously via the cephalic vein once daily over 30 mins. Cats that began treatment with remdesivir were switched to oral GS-441524 once their clinical condition improved and they could tolerate oral medication. In all cases, the daily dose of oral GS-441524 was administered in two divided doses given approximately 12 h apart. Previous reports have noted cases of loss of appetite due to vomiting after oral GS-441524 administration.¹⁶ Therefore, based on clinical judgement and to minimise the potential risk of gastrointestinal signs, oral maropitant citrate (Cerenia; Zoetis Japan) was administered prophylactically to all cats for 4–6 days after starting oral GS-441524 administration.

High-dose administration was continued for 10–14 days. If significant clinical improvement was observed – such as increased appetite, resolution of effusion or improved blood test parameters – the dose was then reduced to a maintenance level based on the original FIP type (⩾12 mg/kg for the effusive or non-effusive form and ⩾15 mg/kg for cases with ocular involvement). Neurological signs associated with FIP have been reported to improve early after the initiation of antiviral therapy;^6,11,24 therefore, the initial high-dose period was set at 10–14 days. It is known that the plasma concentrations of orally administered GS-441524 vary considerably among individual cats;²⁵ therefore, in the present study, both the initial and maintenance doses were administered by dividing the total daily dose into two doses given twice daily approximately 12 h apart. The dose was adjusted according to weight gain to ensure accurate mg/kg dosing.

Treatment period observation

Cats treated with remdesivir were managed as inpatients and monitored daily for treatment response. Once oral administration became feasible, they were discharged to home-based care. In cases where treatment was initiated with oral GS-441524, medication was administered at home from the start of treatment. Treatment response was monitored every 2 weeks from the start of therapy. Follow-up assessments included physical examination, blood tests, radiography and ultrasonography, depending on clinical signs. At each follow-up visit, blood tests were performed and included measurement of SAA and α1AG, as well as haematology and serum biochemistry. Abdominal ultrasonography was performed to assess not only clinical findings associated with FIP but also the presence of urinary tract calculi in the kidneys and urinary bladder.

Criteria for treatment termination

Treatment with oral GS-441524 was discontinued based on two predefined sets of discontinuation criteria: one for early discontinuation before 12 weeks and one for discontinuation at week 12.

Early treatment discontinuation (before 12 weeks) was permitted when all the following criteria were met:

Improvement of all clinical signs, including appetite, weight gain, and resolution of effusion and granulomatous lesions.

The SAA and α1AG concentrations were within the reference intervals (RIs) (SAA <6 mg/l; α1AG ⩽0.5 g/l¹⁹) for at least 2 weeks.

If the criteria for early discontinuation were not fulfilled, treatment was continued for a maximum duration of 12 weeks. In such cases, treatment was discontinued at week 12 provided that clinical signs had improved, regardless of SAA or α1AG concentrations.

SAA concentrations were measured using an in-house analyser (Quick LASAY 101; Shima Laboratories). As there is no universally accepted RI for SAA in cats and reported values vary depending on the assay used, SAA concentrations were interpreted using the RIs (<6 mg/l) provided. This RI encompasses values previously reported for clinically healthy cats, in which SAA concentrations are typically low or undetectable.^26,27 α1AG concentrations were measured at a commercial laboratory (Fujifilm Vet Systems) using a latex agglutination immunoassay. SAA and α1AG concentrations were measured in serum and were analysed once per sample.

After the completion of oral GS-441524 treatment, a 3-month follow-up period was conducted to assess relapse. Physical examinations, blood tests, radiog-raphy and ultrasonography were conducted at 2, 6 and 12 weeks after treatment to assess for relapse of FIP.

Results

Signalment

A total of 30 cats were included in this study. Of them, 12 were purebred: Munchkin (n = 5), Norwegian Forest Cat (n = 3) and one each of American Shorthair, Persian, Scottish Fold and Minuet. The remaining 18 were domestic shorthair and longhair cats. The median age was 9 months (interquartile range [IQR] 5–31, range 3–139). The cats included seven intact males, 11 castrated males, two intact females and 10 spayed females.

Clinical signs

In total, 20 cats presented with effusions, whereas 10 did not. Among those with effusions, 16 had ascites, three had pleural effusion and one had thoracoabdominal effusion. In addition to effusion, nine cats exhibited granulomatous lesions. Among the 10 non-effusive cases, two cats had both ocular signs and granulomatous lesions, and two exhibited ocular signs alone. No cases exhibited neurological signs.

RT-qPCR testing

RT-qPCR testing of effusions was performed in 18 cats. In two cats with effusions that were difficult to collect and in 10 cats without effusions, RT-qPCR was instead conducted on whole blood, based on a strong clinical suspicion of FIP from clinical signs, blood test abnormalities (increased SAA and α1AG concentrations, anaemia, hyperglobulinemia, a decreased A:G ratio and jaundice) and imaging findings. All RT-qPCR results were positive in each of the samples. As immunohistochemical examination was not performed in any of the cases, all cases were considered to have a very high suspicion of FIP.

Treatment selection and progress

A total of 11 cats were on remdesivir (median starting dose 21.2 mg/kg [range 20.0–21.6]), while 19 began treatment with oral GS-441524 (median starting dose 23.1 mg/kg [range 20.7–27.8]). One cat that started on remdesivir died during the treatment period due to deterioration in clinical condition (survival time 6 days). This cat had both pleural and peritoneal effusion with granulomatous lesions.

The remaining 10 cats treated with remdesivir and all 19 cats treated with oral GS-441524 responded well to the initial treatment and showed significant clinical improvement (median 3 days [range 1–6]). Cats that initially received remdesivir were switched to oral GS after a median of 5 days (range 2–7) and the treatment was continued. The 29 cats that responded to treatment received high-dose therapy for a median of 14 days (range 10–18), after which the dose was reduced to the maintenance level (median maintenance dose 16.5 mg/kg [range 13.0–24.4]) and continued. In all cases, maropitant citrate was administered concomitantly for 4–6 days after the initiation of oral GS.

Treatment period

Treatment was discontinued in cats that met the termination criteria, while treatment response was monitored every 2 weeks. In all cases, no deterioration or relapse was observed during treatment after clinical signs improved. In total, 22 cats completed treatment in less than 12 weeks, with a median treatment duration of 54 days (IQR 45–57, range 41–71). Of these 22 cats, 15 had the effusive type and seven had the non-effusive type. The non-effusive group included three cats with ocular signs. Among the cases in which treatment was completed in less than 12 weeks, 9/10 cats that survived after remdesivir administration were included.

The remaining seven cats exhibited clinical improvement and had treatment discontinued at 12 weeks, even though the SAA and α1AG criteria were not fully met. There were four cases that did not meet the criteria for α1AG, two cases that did not meet the criteria for SAA and one case that did not meet the criteria for both α1AG and SAA. Of the seven cats, two cats had hyperglobulinaemia at 12 weeks. Table 1 shows the progress of SAA and α1AG in cases where treatment was terminated in less than 12 weeks and in cases where treatment was continued for 12 weeks.

Table 1

Comparison of serum amyloid A (SAA) and alpha-1 acid glycoprotein (α1AG) concentrations at diagnosis and during treatment between cats that completed therapy in less than 12 weeks and those that continued treatment for 12 weeks

Time period (weeks)	SAA (mg/l)		α1AG (g/l)
	<12* (n = 22)	12^† (n = 7)	<12* (n = 22)	12^† (n = 7)
Diagnosis	150.01	150.01 (130.27–150.01)	2.01	2.01
2 weeks	4.38 (3.74–22.97)	41.37 (5.48–117.22)	1.13 (0.61–1.44)	1.23 (1.06–1.43)
4 weeks	3.74 (3.74–4.78)	8.23 (3.74–26.24)	0.44 (0.38–0.55)	0.69 (0.57–0.92)
6 weeks	3.74 (3.74–4.57)	4.03 (3.74–17.85)	0.40 (0.33–0.48)	0.55 (0.47–0.85)
8 weeks	3.74	3.74 (3.74–10.7)	0.41 (0.33–0.46)	0.59 (0.43–0.87)

Data are median (interquartile range [IQR]). IQRs were omitted when equal to the median value. All cases were compared up to week 8, when the timing of testing coincided. The SAA values >150.00 mg/l were recorded as 150.01 mg/l and values <3.75 mg/l were recorded as 3.74 mg/l. The α1AG values >2.00 g/l were recorded as 2.01 g/l. Reference intervals: SAA <6 mg/l; α1AG ⩽0.5 g/l

<12 weeks: cats that completed treatment in less than 12 weeks

†

12 weeks: cats that received treatment for 12 weeks

All cats were followed for at least 3 months after completing oral GS-441524 treatment. In all cases, no deterioration in clinical signs or marked increases in SAA and α1AG concentrations were observed at 2, 6 and 12 weeks after discontinuation of treatment, indicating no evidence of FIP relapse.

Adverse reactions

No adverse reactions, such as vomiting, were observed after remdesivir administration. Similarly, no issues with vomiting or anorexia occurred after oral GS-441524 initiation. During the administration period, elevated alanine aminotransferase (ALT) concentrations were observed in 17 cats, but none showed clinical signs necessitating discontinuation of administration or adjustment. The median of the maximum ALT level during treatment was 106 U/l (IQR 78–136). Abdominal ultrasonography was conducted in 24/29 cats, and no evidence of urinary stone formation was detected in any of these cats during treatment or throughout the follow-up period.

Discussion

In this study, achieving normalisation of both SAA and α1AG concentrations was used as the criterion for early termination of GS-441524 treatment before the maximum 12-week course. If these criteria were not met, treatment was continued up to 12 weeks according to the study protocol. In total, 22/29 (75.9%) cats met the SAA- and α1AG-based criteria and discontinued treatment earlier than 12 weeks, while the remaining seven cats continued treatment until completion at 12 weeks. No relapses were observed in any cats during a follow-up period of at least 3 months after the completion of oral GS-441524 therapy. These findings suggest that, in this selected cohort of cats, the criteria used in this study may be useful for determining when treatment with injectable remdesivir transient to oral GS-441524 or oral GS441524 can be discontinued before the 12-week period.

The duration of treatment for FIP with GS-441524 was initially reported to require a 12-week course, taking into consideration the risk of relapse after therapy.⁶ Although subsequent dose escalation has been implemented in response to changes in formulation and with the aim of reducing relapse rates, a 12-week treatment period has continued to be widely adopted.^11
–13 Although this duration yields good outcomes, long-term treatment with injectable remdesivir transient to oral GS-441524 or oral GS-441524 is often expensive. Although these treatments can be effective, they are not always feasible, as financial constraints and the stress associated with prolonged treatment may render them impractical. Therefore, treatment strategies that reduce drug exposure while maintaining efficacy should be considered.

Previous studies have reported clinical improvement with treatment durations shorter than 12 weeks; however, in some cases, treatment was not intentionally discontinued according to a predefined shortened protocol.⁷ Other reports have adopted predefined shortened regimens, such as a 6-week protocol with standardised dosing.¹⁵ These differences in study design and dosing strategies limit direct comparison but suggest that clearly defined and intentional treatment-shortening protocols may influence treatment outcomes. These findings suggest that certain cases may respond to shorter treatment courses if protocols are appropriately adjusted. When clinical signs of FIP recur after treatment cessation, it is often difficult to distinguish relapse from reinfection.²⁸ Further studies are required to clarify these classifications. However, considering that relapse often occurs during or shortly after treatment cessation,⁷ it may be due to incomplete viral elimination during the treatment period. As there is no reliable method to confirm sufficient viral clearance, decisions regarding treatment discontinuation must be based on other clinical and laboratory parameters. Given that some cats relapse even after completing a 12-week treatment regimen, the optimal duration of therapy likely varies depending on disease severity and treatment response. Therefore, when considering treatment up to the standard 12-week duration, evaluating treatment discontinuation on a case-by-case basis may be more appropriate than applying a uniform treatment period to all cases.

We previously reported that remdesivir and GS-441524 therapy could be discontinued based on improvements in clinical signs, the A:G ratio, SAA and α1AG concentrations.¹⁴ In that report, adjunctive therapy with mefloquine was used after GS-441524 discontinuation to minimise relapse risk. However, the clinical efficacy of mefloquine against FIP remains unclear, and its antiviral activity is less well supported by clinical evidence than that of remdesivir and GS-441524.^4,6,20 Therefore, the necessity of adjunctive mefloquine therapy remains uncertain. In the present study, no relapses were observed after early discontinuation of treatment without adjunctive mefloquine. These findings suggest that early discontinuation may be feasible without adjunctive therapy. However, the specific role of mefloquine in relapse prevention warrants further investigation.

The A:G ratio may remain abnormal in some cases despite clinical improvement and may not normalise even after 12 weeks of treatment. Furthermore, the A:G ratio is a non-specific composite parameter that can be influenced by various inflammatory and non-inflammatory conditions unrelated to FIP.^29,30 Therefore, in this study, we investigated whether it is essential as a criterion for treatment termination. APPs are also non-specific indicators. Although other major inflammatory diseases were excluded at the time of diagnosing FIP, their development during the treatment period cannot be ruled out. Although both the A:G ratio and APPs are non-specific markers, they reflect different biological processes. Acute phase proteins such as SAA and α1AG primarily indicate current inflammatory activity and tend to show dynamic changes in response to treatment, whereas the A:G ratio represents cumulative alterations in albumin synthesis and globulin production, which may persist despite clinical and inflammatory improvement.

Although SAA and α1AG did not normalise in all cats by week 12, their behaviour should not be considered equivalent to that of the A:G ratio. Therefore, APPs were interpreted with caution, and cats were carefully re-evaluated as clinically indicated for possible concurrent inflammatory conditions. In cats with FIP, SAA and α1AG have been reported to decrease in response to treatment in many cases and to be useful indicators of disease activity, relapse and reinfection.^7,11,19,21 Accordingly, we considered SAA and α1AG to be indicators of FIP improvement when assessed in conjunction with improvement in clinical signs and incorporated them into the termination criteria. The A:G ratio was not used, and treatment termination within 12 weeks was determined based on improvement in SAA and α1AG. Using these termination criteria, no relapses were observed, including in cases in which treatment was discontinued within 12 weeks. These findings suggest that the A:G ratio may not be necessary when deciding to end treatment. By reducing the number of criteria required for treatment termination, the proportion of cases eligible for discontinuation within 12 weeks increased compared with previous reports. Therefore, the treatment termination criteria used in this study may be applicable to a broader range of FIP cases. Furthermore, as no relapses were observed in any cats in this study, including those with non-effusive and ocular involvement, this approach may be applicable to a broader range of FIP cases within the spectrum represented here.

In the present study, early treatment discontinuation was achieved in most cats that required remdesivir administration. Remdesivir was indicated for cats in which oral administration was difficult because of compromised general condition and was therefore preferentially used in cases showing less favourable clinical features at presentation. Accordingly, treatment shortening was feasible not only in cats with clinically mild disease but also in those with less favourable clinical characteristics, suggesting that the required treatment duration may not necessarily correlate with the clinical features observed at diagnosis. However, the number of cats treated with remdesivir was limited, and we were unable to perform a sufficiently powered statistical analysis to evaluate the relationships among treatment modality, trends in disease severity and treatment duration. Therefore, although these observations are clinically interesting, they should be interpreted with caution. Further studies including larger numbers of cases are required to determine whether treatment modality or baseline clinical status truly influences the feasibility of treatment shortening.

An additional important observation in this study is the different clinical roles suggested for SAA and α1AG during the treatment course. SAA concentrations decreased early after initiation of therapy and, although minor fluctuations were observed in some cases thereafter, no clinically relevant re-elevation was noted during the observation period in this study. SAA is recognised as a major acute phase protein that reflects inflammatory activity in cats with FIP and has been reported to decrease during effective treatment.^15,26,31 This suggests that SAA may be useful as an early indicator of treatment response. In contrast, although α1AG tended to decrease more gradually in our cohort, decisions to discontinue treatment early were often guided by whether α1AG concentrations had fallen within the RI. α1AG has been reported to be elevated in cats with FIP and to reflect inflammatory status;^26,32 however, published data directly comparing the temporal dynamics of SAA and α1AG during treatment remain limited. Although both APPs are non-specific markers, their biological characteristics differ. SAA primarily reflects current inflammatory activity and may respond dynamically to changes in disease status, whereas α1AG represents a broader acute phase response that may persist beyond initial clinical improvement. Taken together, these findings suggest a complementary role for these APPs, whereby SAA may be useful for early assessment of treatment efficacy, while α1AG may provide additional information when considering the appropriateness of treatment termination in clinical practice.

In this study, treatment was discontinued at 12 weeks even in cases that did not meet the predefined criteria for early treatment discontinuation, and no relapses were observed during the 3-month follow-up period after treatment cessation. Normalisation of SAA and α1AG concentrations was used as a criterion for early treatment discontinuation before 12 weeks. However, at week 12, treatment was discontinued primarily based on improvement in clinical signs, regardless of whether α1AG concentrations had fully normalised. Although persistent elevation of α1AG has been reported to be associated with an increased risk of relapse, this was not observed in the present study, even in cats in which α1AG concentrations remained above the RI at week 12. Although this finding is noteworthy, it should be interpreted with caution given the limited follow-up period and sample size, and does not establish a causal relationship between the dosing regimen and relapse risk.

Furthermore, no obvious adverse clinical effects related to high-dose induction therapy were observed in this study, suggesting that this regimen was well tolerated in the cats studied. Although urinary tract calculi composed of GS-441524 have been reported at apparently high doses,^33,34 abdominal ultrasonography was performed in 24/29 cats in the present study and no evidence of urinary stone formation was detected in these cases. Nevertheless, this observation should be interpreted cautiously as this study included only a small number of cats; therefore, it cannot be concluded from our data that high-dose induction therapy is either superior in efficacy or safer than standard dosing protocols. Determining whether high-dose induction therapy offers any clinical advantage over other dosing regimens will require direct comparative studies with adequate sample sizes and systematic evaluation of clinical outcomes, adverse events and cost-effectiveness.

In this study, maropitant was administered prophylactically to all cats at the initiation of oral GS-441524 therapy. Although gastrointestinal adverse effects, including nausea and vomiting, have been reported infrequently at standard doses of GS-441524, several cats in our clinical experience developed vomiting shortly after treatment initiation, which was associated with reduced appetite. Therefore, maropitant was used preventively based on clinical judgement to minimise the potential risk of gastrointestinal signs. This approach was empirical and should not be interpreted as a recommendation for routine prophylactic antiemetic use in cats receiving standard doses of GS-441524. Notably, no cases of vomiting were observed during the treatment period in this study; therefore, it remains unclear whether vomiting represents an adverse effect associated with high-dose GS-441524 administration. Further studies are warranted to clarify the relationship between GS-441524 dosage and the occurrence of gastrointestinal adverse effects. In this study, the duration of the initial high-dose phase was set at 10–14 days based on clinical observations that neurological signs in cats with FIP may improve early after the initiation of antiviral therapy.^6,11,22 However, the precise time course of neurological recovery has not been systematically evaluated in peer-reviewed studies. Therefore, this treatment strategy was empirical and guided by clinical experience and expert opinion rather than by established evidence.

A limitation of this study is the absence of relapse cases, which made it impossible to determine whether the FIP termination criteria used were necessary conditions. Furthermore, it was difficult to compare the results with conventional treatment protocols, and whether the criteria for discontinuing treatment used in this study can be applied to protocols other than high-dose induction protocols without increasing the risk of relapse has not been fully investigated. In cases of non-effusive FIP at the time of diagnosis, where histopathological examination was challenging, a strong suspicion was determined based on other test findings and PCR test results from whole blood. In this study, clinical diagnosis was made by considering treatment response. However, FCoV RT-PCR testing using whole blood has low sensitivity, and the definitive diagnosis of FIP can only be made through histopathological examination; therefore, further cases with confirmed diagnoses are necessary. In addition, abdominal ultrasonography to assess urinary tract calculi was not performed in all cats; therefore, the presence of such calculi cannot be completely excluded in those that were not examined. Because SAA and α1AG were used as the criteria for discontinuing treatment, cases limited to neurological signs in which these markers may not increase significantly were excluded.^17,18 If treatment discontinuation is to be determined based on factors other than treatment duration, alternative termination criteria should be considered.

Conclusions

In this study, we demonstrated that, in this selected cohort, GS-441524 treatment for FIP could be discontinued based on improvements in clinical signs and SAA and α1AG concentrations without observed relapse or major adverse effects during the follow-up period. By util-ising clinical response-based criteria rather than a fixed treatment duration, treatment may be individualised and the treatment period potentially shortened to less than 12 weeks. These findings suggest a promising, more accessible treatment strategy for selected FIP cases.

Footnotes

Acknowledgements

We would like to thank Editage () for English language editing.

Accepted: 5 March 2026

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers, tissues and samples) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Tsuyoshi Kamiyoshi

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High-dose induction therapy and treatment termination criteria for feline infectious peritonitis with remdesivir and GS-441524

Abstract

Objectives

Methods

Results

Conclusions and relevance

Plain language summary

Keywords

Introduction

Materials and methods

Diagnosis

Treatment protocol

Treatment period observation

Criteria for treatment termination

Results

Signalment

Clinical signs

RT-qPCR testing

Treatment selection and progress

Treatment period

Adverse reactions

Discussion

Conclusions

Footnotes

Acknowledgements

Conflict of interest

Funding

Ethical approval

Informed consent

ORCID iD

References