Abstract
Objectives
The aim of the study was to assess long-term ciclosporin oral solution compliance in cats treated for feline atopic skin syndrome (FASS).
Methods
A survey was sent by email to 114 owners who had administered ciclosporin oral solution to their cats for FASS.
Results
In total, 42 owners completed the survey. The population was composed of 30 domestic shorthair cats and 12 pure breeds. There were 20 males and 22 females, and the median age was 5.5 years. Ciclosporin oral solution was administered directly into the mouth in 32/42 (76%) and with food/other in 10/42 (24%) cats. The administration was considered easy in 18/42 (43%) cats, difficult in 23/42 (55%) and impossible in 1/42 (2%). Treatment was stopped in 25/42 (60%) cats. The causes were as follows: administration difficulty (nine cats, 21%); complete resolution (four cats, 10%); treatment failure (four cats, 10%); price (two cats, 4%); and other causes (two deaths, two neoplasia, one adverse effect and one lack of compliance). Adverse effects involving clinical signs were reported in 25 (60%) cats: ptyalism (8/42); dysorexia/anorexia (6/42); vomiting (4/42); diarrhoea (4/42); gingival hyperplasia (1/42); and a combination of vomiting, diarrhoea and ptyalism (2/42). In addition, altered behaviour was reported in 27/42 (64%) cats: hiding in seven cats; scared of owner in 10 cats; modification of sleeping or playing activity in six cats; inappropriate urination/defecation in two cats; aggression in one cat; and all of the above in one cat.
Conclusions and relevance
In total, 24 (57%) cats had adverse effects involving both clinical signs and altered behaviour, and only six cats had either adverse clinical signs or behavioural changes. This survey showed that behavioural changes appear to be underestimated in the cats treated with ciclosporin oral solution and this could cause treatment failure due to lack of compliance. Larger-scale studies are needed to confirm these preliminary results.
Keywords: Ciclosporin, FASS, compliance, behaviour
Introduction
Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats. Ciclosporin oral solution has been approved for the treatment of feline atopic skin syndrome (FASS) in cats since 2014. It is used widely because, along with systemic corticosteroids, it is the most effective treatment of chronic FASS. 1 Adverse effects (most commonly gastrointestinal signs) have been reported and can be the cause of early cessation of treatment.2 –4
In addition, bitterness can also limit the use of the oral solution. We hypothesised that bitter taste and adverse effects could generate a significant lack of compliance and behaviour disturbances.
We assessed the owner-reported compliance with administration of ciclosporin oral solution and the adverse effects in cats with chronic FASS.
Materials and methods
Animals
All of the cats were presented to a referral dermatology consultation between 2015 and 2020 with clinical signs compatible with FASS. 5 Cats were eligible for ciclosporin oral solution treatment after an appropriate diagnostic work-up (strict 2-month flea control, lack of response to an 8-week elimination diet, no skin infection and no ectoparasites). In addition, cats had to have a negative feline leukaemia virus antigen test and negative serology for feline immunodeficiency virus before starting ciclosporin oral solution treatment. Cats aged older than 8 years had to have a biochemistry profile within the reference limits. A minimum course of 1 month of ciclosporin oral solution administration was required to enter the study.
Survey
Owners who accepted the General Data Protection Regulation conditions were invited twice by email to answer a nine-question survey using SurveyMonkey (Table 1): (1) breed, age and sex; (2) age at first administration; (3) mode of administration; (4) ease of administration; (5) duration of treatment; (6) reason for treatment discontinuation; (7) clinical adverse effects; and (8) behavioural change. The questionnaire was short and anonymous to increase the response rate. Data were collected from the pet owners 1 month later.
Table 1.
Results of the survey on ciclosporin administration, efficacy and adverse effects in 42 cats
| Questions | Response | Number of cats (%) |
|---|---|---|
| Mode of administration | Dropped on food | 2 (5) |
| Mixed with food | 7 (17) | |
| Directly in the mouth | 32 (76) | |
| Other | 1 (2) | |
| Ease of administration | Impossible | 1 (2) |
| Very difficult | 14 (33) | |
| Difficult | 9 (21) | |
| Easy | 16 (38) | |
| Very easy | 2 (5) | |
| Efficacy | Fully cured during treatment | 19 (45) |
| Partial response | 16 (38) | |
| Lack of efficacy | 7 (17) | |
| Duration of treatment | Visual scale (weeks 0–100) | |
| ⩽4 weeks | 6 | |
| 5–25 weeks | 24 | |
| 26–50 weeks | 3 | |
| 50–75 weeks | 1 | |
| >75 weeks | 8 | |
| Reason of treatment discontinuation | Treatment continued | 17 (40) |
| Administration difficulty | 9 (21) | |
| Adverse effects | 1 (2) | |
| Treatment failure | 4 (10) | |
| Complete resolution | 4 (10) | |
| Price | 2 (5) | |
| Other (death, neoplasia) | 5 (12) | |
| Clinical adverse effects | None | 17 (40) |
| Ptyalism | 8 (19) | |
| Vomiting | 4 (10) | |
| Dysorexia | 5 (12) | |
| Anorexia | 1 (2) | |
| Soft stools or diarrhoea | 4 (10) | |
| Gingival hyperplasia | 1 (2) | |
| Ptyalism/vomiting/diarrhoea | 2 (5) | |
| Behavioural changes | None | 15 (36) |
| Hiding | 7 (17) | |
| Scared of owners | 10 (24) | |
| Plays less | 2 (5) | |
| Sleeps less | 1 (2) | |
| Sleeps more | 3 (7) | |
| Aggression | 1 (2) | |
| Inappropriate elimination | 2 (5) | |
| Hiding/altered sleep/inappropriate elimination/aggression/scared of owners | 1 (2) |
Ciclosporin oral solution
All cats were treated with ciclosporin at 100 mg/ml oral solution (Modulis, Ceva or Cyclavance; Virbac).
Results
Questionnaires
Of the 114 owners, 42 (37%) responded to and completed the whole survey 1 month after receiving it. All cats were treated following the manufacturer’s recommendations: 7 mg/kg (6.5–9 mg/kg) q24h then every other day when clinical signs where controlled. It was not possible to retrospectively collect clinical and biological data since the questionnaire was anonymous, short and focused on compliance with treatment and adverse effects.
Breed, age and sex
The cat population was composed of 30 (70%) domestic shorthair cats, five Maine Coons, two Birman cats and five other breeds. There were 20 males and 22 females with a median age of 5.5 years (range 1–15). For all cats, it was their first administration of ciclosporin.
Mode of administration
Ciclosporin oral solution was administered directly in the mouth in 32/42 (76%) cats and with food/other in 10/42 (24%) cats (poured on dry food, mixed with wet food or in one other case, mixed with yoghurt).
Ease of administration
Administration was considered easy in 18/42 (43%) cats, difficult in 23/42 (55%) cats and impossible in one cat (2%). In one cat, the owner reported that they were unable to administer the ciclosporin oral suspension despite numerous techniques (directly in the mouth, mixed with cat food, cheese, milk, butter, tuna, fish oil) (Table 1).
Efficacy
The cats’ owners considered the treatment as fully effective in 19/42 cats, partially effective in 16/42 cats and ineffective in 7/42 cats, including two cats that died during the follow-up period (see below).
Duration of treatment
The duration of treatment was in the range of 0–100 weeks (median 9 weeks): ⩽4 weeks, six cats; 5–25 weeks, 24 cats; 26–50 weeks, three cats; 50–75 weeks, one cat; and >75 weeks, eight cats.
Reason for treatment discontinuation
The treatment was discontinued in 25/42 (60%) cats. The causes were as follows: administration difficulty in 9/42 (21%) cats; complete resolution in four (10%) cats; treatment failure in four (10%) cats; price in two (4%) cats; and other causes (two deaths, two neoplasia, one adverse effects and one lack of compliance).
Adverse effects
In total, 12 (29%) cats were reported not to have experienced adverse effects.
Adverse effects were reported in 30/42 (71%) cats. In total, 24 (57%) cats were reported to have adverse effects involving clinical signs and behavioural changes, three (7%) cats had clinical signs only (including two deaths); and a further 3 (7%) cats had behavioural changes only. In the 25/42 (60%) cats reported to have adverse clinical signs, these were: ptyalism (8/42); dysorexia-anorexia (6/42); vomiting (4/42); diarrhoea (4/42); gingival hyperplasia (1/42); and a combination of vomiting, diarrhoea and ptyalism (2/42). Two cats died (no cause reported) and one cat developed neoplasia >100 weeks after initiating treatment with ciclosporin oral solution.
Behavioural changes were reported in 27 (64%) cats: scared of owner (10 cats); hiding (seven cats); altered sleep or play (six cats); inappropriate urination/defecation (two cats); aggression towards the owner (one cat); and all of the above (one cat).
Discussion
This small survey confirmed the high efficacy of ciclosporin oral solution in the treatment of FASS (45% effective, 38% partially effective) despite challenges with compliance.
The aim of this retrospective case series survey was to document the occurrence of adverse effects involving clinical signs and behavioural changes in cats receiving ciclosporin oral solution to treat FASS. Adverse effects were frequent (71%) and the frequency of clinical signs reported in this survey was comparable to previous studies: vomiting and diarrhoea (14–35%); weight loss (16%); dysorexia/anorexia (14%); and gingival hyperplasia (4%).2–4 Ptyalism, which has only been described in two previous studies,2,3 was reported in 24% of cats in this survey. This could have been due to the propylene glycol, 2 other excipients (ie, ethanol) or the bitterness of the ciclosporin oral solution. It was one of the major causes of treatment cessation. In most studies, treatment discontinuation is reportedly due to adverse effects.2–4 In this survey, adverse effects were also involved, but difficulty in administering treatment led to treatment being stopped in nine (21%) cats. These difficulties were worsened by ptyalism and behavioural changes. Interestingly, this survey showed that behavioural changes were more frequent than described previously: 64% vs 9% 3 and were associated with clinical adverse effects in almost all cases.
The occurrence of behavioural changes as an adverse effect of the treatment of feline chronic allergic skin diseases has not been studied sufficiently, despite the importance of patient wellbeing in the quality of life of the cat and the owner during treatment. Moreover, behavioural changes can be associated with worsening pruritus in some cats and has been described as the primary cause in several cases.6 –8
This study has a number of limitations, including the small number of respondents/cats, the response rate (37%), and the retrospective and anonymous design. Larger-scale prospective, multicentre studies are needed to confirm these preliminary findings.
Conclusions
This survey highlights the importance of adverse effects (71%), especially behavioural changes associated with the administration of ciclosporin oral solution to cats. The impact of behavioural changes is underestimated even though it appears to be one of the major reasons for the lack of compliance with ciclosporin oral solution treatment and may limit the use of this type of product in cats. Taking these data into account, there appears to be a need to develop new routes of administration (subcutaneous, 9 transdermal) or a change in the composition (different active ingredient, more acceptable/less bitter formulation, flavour with the limit of possible allergy) in order to improve patient welfare and owner compliance, and hence the success of the treatment.
Acknowledgments
The authors would like to thank the cat owners who completed this survey. The authors would also like to thank Aurore Laprais for her help in manuscript writing.
Footnotes
Accepted: 27 November 2023
Author note: The results of this study were presented, in part, as an abstract presentation at the 2021 ESVD-ECVD Congress.
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: This work did not involve the use of animals and therefore ethical approval was not specifically required for publication in JFMS.
Informed consent: This work did not involve the use of animals (including cadavers) and therefore informed consent was not required. No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.
ORCID iD: Pascal Prelaud 
https://orcid.org/0000-0002-8084-0039
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