Adherence to veterinary recommendations for ectoparasiticides purchased by cat owners in the United States of America.

Background: Safe and effective �ea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at United States of America (U.S.) veterinary clinics were obtained for three topical feline �ea and tick ectoparasiticides. One medication, �uralaner, had a 12-week redosing interval, while two other medications (�pronil/s-methoprene/pyriproxyfen ;imidacloprid/pyriproxyfen ) were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products. Methods: Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing 41,630 cats. Results: Cat owners purchased an average of 1.5 doses of �uralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly �ea and tick medications respectively purchased 3.6 months (�pronil/s-methoprene/pyriproxyfen combination) and 2.8 months (imidacloprid/pyriproxyfen) annually of each of the two medications. Average yearly cat owner purchases of �uralaner provide a signi�cantly longer duration of coverage than for cat owners purchasing �pronil/s-methoprene/pyriproxyfen (17% more) or imidacloprid/pyriproxyfen (50% more). Conclusion: Cat owners who obtained a �ea and tick treatment with a 12-week redosing interval (�uralaner) protected their cats for up to 17% or 50% longer duration each year compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of �ea and tick coverage to come closer to achieving veterinary recommendations.


Background
In primary care veterinary practice, ea and tick control is an essential component of the preventive healthcare strategy for cats.This is because of the high prevalence of ea infestation, the year-round risk of ticks, the risk of ea allergy dermatitis (FAD), the pathogens that eas and ticks vector, and the introduction of eas into the home [1,2].
Fleas, particularly Ctenocephalides felis felis, are very common and perhaps the most clinically important ectoparasite of cats and dogs worldwide [3][4][5].Flea-related diseases could account for more than half of dermatologic cases presented to companion animal veterinarians [5][6][7].Results of European studies con rm that levels of feline ea infestation are variable, and can exceed 70% in an untreated population [6].A study of free-roaming cats in the central United States of America (U.S.) in 2014 found eas on 71.6% and ticks on 18.7% of trapped cats [8].A multi-center study conducted at veterinary facilities in nine European countries evaluated 1519 client-owned cats untreated with ectoparasiticides in the preceding month [9] and found an overall 15.5% ea infestation prevalence.A ea infestation prevalence of 22.9% was reported in feline patients at 13 veterinary practices in Hungary [10], and a 21.1% prevalence at 31 practices in the United Kingdom (U.K.) [11].In both the Hungarian and U.K. studies, the ea infestation prevalence in cats was considerably greater than the prevalence in dogs evaluated concurrently at the same sites.Moreover, in the U.K. study the prevalence of FAD lesions in cats (8.0%) was signi cantly greater (P < 0.001) than in dogs (6.8%).Approximately half of the pet owners in the U.K.
study whose pets harbored eas were unaware that their animals were infested.Other investigators con rm that apparently healthy cats can harbor low levels of ea infestation, in some cases the lack of ea awareness is apparently a result of overgrooming by the cat [12].Feral cats, untreated rural cats and indoor-outdoor cats may have considerably higher levels of infestation, associated with their increased outdoor exposure to eas , than indoor cats [3,10].
Fluralaner kills newly emerging adult eas on the host before they start laying eggs, which in untreated animals would fall off the host into the environment and develop into ea larvae and pupae.Interrupting on-animal egg production disrupts the ea life cycle, depleting the ea population in the home surroundings and preventing subsequent re-infestation of the host [23].Fluralaner has demonstrated onset of ea adulticidal activity within 2 hours after topical administration [16].As home environment studies have indicated [13,24], a rapid speed of kill and long duration of action prevent re-infestation of the host and home environment by eliminating all ea life stages from the environment.
In an effort to sample the veterinarian recommendations for ea and tick prevention in dogs, approximately 30 veterinarians in each of the US, UK and Australia were surveyed as part of a larger pet owner survey [25].For dogs, veterinarians recommended approximately 12 months of protection against eas and 9-12 months protection against ticks per year.The Companion Animal Parasite Council recommends year-round ectoparasite control for dogs and cats [26].
Feline ea and tick control before the approval of uralaner commonly involved ectoparasiticide administration to cats at monthly intervals.Weak owner adherence with recommended ea treatments may lead to a failure or delay in administering follow-on doses at the required time.This lack of adherence leads to persistence of the ea population in the household, and failure to follow recommended treatment recommendations is identi ed as the most common cause of ea treatment failure [27].Lack of treatment adherence is often followed by a perceived lack of e cacy and is a vital issue in clinical practice because it affects the owners' con dence in the prescriber and medication as well as the actual treatment success.
One option for veterinary practitioners to potentially increase adherence to veterinary recommendations for ea and tick protection is through prescription of an extended duration product.This approach requires the cat owner to administer fewer doses over the same period of time.Prior studies across an array of drug classes in human and veterinary medicine have consistently shown an inverse relationship between treatment adherence and the complexity (particularly higher number of doses) and convenience of the therapeutic regimen [28].
The objective of the study reported here was to compare the annual duration of ea and tick treatment purchased by cat owners in the USA who were prescribed the long duration treatment of uralaner with the duration purchased by cat owners prescribed monthly ectoparasiticides.

Study design
Client topical feline ea and tick treatment purchase transactions from veterinary clinics throughout the USA.were evaluated retrospectively.Transaction records were obtained from a proprietary medical records data collection service (VetInformatics, Inc., Rolling Meadows, Ill, USA).Transactional record data did not contain information on the names or addresses of the cat, the owner or the veterinary clinic.Code numbers had been assigned which allowed serial transactions to be matched to individual feline patients without exposing the identity of the clinic or cat owner.These data were used to calculate the average annual number of doses purchased by cat-owners of each of three ea and tick medications.The number of doses purchased were then used to calculate the average duration of ea and tick protection for each medication based on the recommended protection duration for each treatment.
The study database (before exclusions) consisted of purchasing records from January 2017 through June 2019 from 671 veterinary practices representing approximately 41,630 cats.Feline ea and tick medications purchased by clients were determined for each individual feline patient for the 12-month period following the purchase index date, de ned as the date of initial feline ea and tick medication purchase.The annual transactions were converted into a duration of coverage period based on the prescribing information for the respective ea and tick medication.
Flea and tick protection duration over the 12 months following the index date could not exceed the total doses purchased that could be reasonably used during this follow-up period.If owners obtained doses late in the 12-month follow-up period, then only the purchased doses that could be used by the end of the 12-month period were included in the coverage calculation.Therefore, the study only used purchased doses obtained in a 12-month period that could be used in 12 months for a speci c cat. Owners who purchased multiple doses in a single transaction were assumed to have administered these doses on time and in a serial manner.

Flea and tick treatments
The pronil/S-methoprene/pyriproxyfen and Imidacloprid/ pyriproxyfen medications used for the study population (Table 1) require monthly re-dosing and one, uralaner, is an extended duration ectoparasiticides with a retreatment interval of 12 weeks.In an online market research study of 250 U.S.
vets, these products were some of the non-heartworm parasiticides for cats with the largest penetration into the U.S. veterinary market [29].

Inclusion and exclusion criteria
Product purchase data were screened to ensure that cats enrolled in the study received only one of the three ea and tick products for the 12-month study period, and that product purchases represented transactions for only one cat.Cats included in the study were ≥ 6 months old on the index day.
Transactions for medications that included endoparasite indications were excluded.Transactions for any species other than cats were excluded.Single transactions that demonstrated purchases in excess of 12 months of ea and tick protection were uncommon and were excluded as likely purchases for more than one cat.Product usage by individual owners was adjusted by removing any doses returned to the clinic for credit.

Statistical evaluation
The mean age, age group, body weight and range were determined for cats enrolled in each product group.The ea and tick medication coverage obtained by cat owners was expressed as a population mean, standard deviation (SD), and percentage for each product and for products grouped by duration.Means were compared across groups using a t test with signi cance set at P < 0.05.

Test population demographics
Three comparator ea and tick medications were examined (Table 1).The geographic distribution of the veterinary clinics in this study was de ned by the clinics that were included in the study database.
Transaction records were obtained from veterinary clinics in the Southeast (50%), Midwest (21%), South Central (15%), West (8%), and Northeast (6%) USA.Demographic pro les for cats in each of the three treatment groups are similar ( Flea and tick treatment purchases were dominated by pet owners who purchased only one or two treatment doses per year, regardless of the medication duration of protection (Table 4, Figure 1).Approximately 67% of cat owners who purchased uralaner obtained one dose and approximately 18% obtained two doses.A large proportion of owners who bought monthly ea and tick treatments limited their annual purchases to either one or two doses as well (34% and 13%, respectively, for pronil/ smethoprene/pyriproxyfen; 51% and 15%, respectively, for imidacloprid/pyriproxyfen).Two doses of uralaner provide up to 5.6 months of treatment coverage, while two doses of a monthly ea and tick treatment provided up to 2 months of coverage.
The distribution of the months of treatment coverage based on annual ectoparasiticide dose purchases is shown (Table 4).A small proportion (8-10%) of cat owners who purchased monthly products obtained 6 doses (6 months) of ea and tick treatment coverage.While veterinarians often recommend a full year of ea protection, a full year of treatment coverage was obtained by an even smaller proportion of cat owners across all brands.

Discussion
The three ectoparasiticides selected for comparison in this study (Table 1) made up the largest proportion of the feline ectoparasiticides provided to cat owners (excluding combinations with endoparasitic activity) as recorded by the veterinary practice transaction database in the U.S. for the study period.All three medications are labelled to treat eas but only uralaner and pronil/s-methoprene/pyriproxyfen are also acaricidal.
Medication purchasing data are a reliable surrogate for medication adherence [30], as long as the purchased medication is administered as recommended.Purchased medication may not be administered as recommended, which means adherence measured from medication purchases would then overestimate true adherence by an unknown amount.A medication administration adherence failure could occur each time the dose needs to be administered.Therefore, more doses to administer leads to a greater probability of failure.This helps to explain why the need to administer fewer doses of a longer acting medication consistently leads to better adherence with prescriber recommendations.Demographic data (Table 2) for participating cats con rm that the study population was similar in age and weight across treatment groups.Cats had a mean age that varied by ≤ 3 months (6.7-6.9 yrs) and a mean weight that varied by ≤ 0.5 kg (4.0 -4.5 kgs) across all treatment groups.
Prior studies comparing dog owner ea and tick medication purchases have shown that owners obtain more months of coverage when they buy an extended duration product [26,31].This study con rms that cat owners similarly will obtain more annual months of ea and tick coverage compared to owners that obtain products with a monthly retreatment interval.Cat owners purchased up to 50% longer duration of ea and tick protection per year when they purchased uralaner, compared with owners who purchased monthly ea and tick medications.
Owner purchases of any medication can be compared with veterinary recommendations to get an assessment of medication adherence.Earlier studies found that veterinarians in the United States recommend 12 months of protection each year against eas and ticks [8,30].Cat owners increased their adherence to this recommendation through use of a product with a longer duration of action.This is also consistent with prior data showing that treatment adherence is inversely related to dosing frequency, a critical convenience factor [28,32].Even with the bene t of extended duration ea and tick medication, cat owners in the U.S. fall well short of full adherence with veterinary recommendations for ea and tick protection duration.
Cats are the most popular pet in the U.S. [33], but they receive much less primary veterinary medical care compared to dogs and 40% of pet cats in one study had not seen a veterinarian during the preceding year compared to 15% of dogs [34].Pet owners surveyed in 2006 took their dogs to the veterinarian an average of 2.3 times per year compared to 1.1 times/year for cats [35].This healthcare underutilization for cats could make poor adherence to treatment recommendations more likely.Therefore, any delivery system that increases owner adherence is likely to improve the preventive health care for their cats.
Year-round ea and tick treatment coverage for cats directly protects the cat, eradicates ea populations in the home environment [13], and helps to reduce the risk of vector transmitted disease [1].However, as seen in this study, cat owners typically acquired only one or two treatment doses, regardless of the duration of the ea and tick medication purchased and few owners obtained full-year ea and tick coverage (Table 4).Therefore, veterinary clinicians and practice staff may want to pay increased attention to owner education and use of repurchase reminders as additional components that contribute to increased owner adherence.
These results for cat owners are consistent with previous results in a large group of U.S. dog owners [36].Dog owners purchased fewer doses and obtained longer ea and tick treatment coverage per year from uralaner compared with monthly medications.Similar results were reported in a large-scale European study comparing owner-purchased canine ea and tick medications, comparing oral uralaner and several monthly oral or topical products [31].Dog owners in Spain purchased fewer uralaner doses per year compared to monthly oral or topical medications but obtained signi cantly more ea and tick coverage.Collectively, these studies con rm that pet owners obtain a relatively longer duration of ea and tick control by use of longer duration ea and tick treatments.

Conclusions
Cat owners who obtained an ectoparasiticide with a 12-week redosing interval protected their cats for a longer period during the year than owners who purchased a monthly treatment.Veterinarians and hospital staff should help cat owners increase the duration of ea and tick protection they obtain to achieve veterinary recommendations and to optimize protection against ectoparasites [26].
Safe and effective feline ea and tick treatment options are therefore an important component of the companion animal armamentarium.The isoxazoline class of parasiticide compounds were introduced in 2013 for use in dogs and 2 years later for use in cats.Fluralaner (Bravecto ® , Merck & Co., Inc., Madison, NJ, USA) is a long-acting isoxazoline class molecule available in oral and topical formulations for use in dogs and in a topical formulation for use on cats, and is indicated for 12 week control of eas and up to

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Figure 1 Cat
Figure 1

Table 2
-methoprene/pyriproxyfen (n = 10,607; 24.5%), and imidacloprid /pyriproxyfen (n = 3,583; 8.3%).Most cats in each treatment group, where a recorded age was available, were 1.1 -8.0 years of age, although > 30% in each group were > 8 years of age and considered mature or senior cats.Most cats in each treatment group had a mean weight between 3.7 kg and 7.3 kg), where a recorded weight was available.Annual purchasing history and ea and tick (F/T) treatment coverage Annual client purchasing history and mean duration of coverage provided by the three F/T medications (Table3) show that cat owners purchased more individual doses per year of each of the two ectoparasiticides which were dosed on a monthly basis compared to the number of uralaner doses, which have an extended duration that is nearly 3X the length of the monthly dose.The extended duration ).Most cats (63.7%) were treated with uralaner (n = 27,440) versus pronil/s

Table 1 .
Topical flea and tick medications used in U.S. feline dosage adherence study

Table 2
Demographics of the cat population from U.S. veterinary practices participating in the topical ectoparasiticide coverage study.

Table 3
Mean annual per-cat ectoparasiticide doses purchased by U.S. cat owners and mean months of flea and tick coverage provided1Mean months of coverage were significantly different between Bravecto Topical and Frontline Gold (t (38045) = 34.1481,P < 0.0001) as well as Bravecto Topical and Advantage II (t (31021) = 50.3001,P < 0.0001).

Table 4
Months of feline flea and tick coverage acquired by U.S. cat owners based on annualized ectoparasiticide purchases a One dose of Bravecto Topical Solution (fluralaner) provides 12 weeks, or 2.79 months, of coverage.