These results show that under field conditions a single oral or spot-on administration of fluralaner is effective in the treatment of generalized demodicosis, whether for treatment of generalized juvenile or adult-onset manifestations of the disease. Evidence of the potent fluralaner effect, in both oral and spot-on formulations, was present as early as 28 days following treatment, when 92.0% of dogs were found to be free of live mites. In comparison, topical imidacloprid-moxidectin did not reach the pre-defined efficacy threshold for generalized demodicosis. At the day 28 assessment, 79.2% of imidacloprid-moxidectin treated dogs were live-mite free, indicating that the miticidal onset was not reaching the 90% threshold at this time.
This is the first controlled field study with fluralaner, and just the second controlled field study with any isoxazoline, to demonstrate field efficacy in the treatment of generalized demodicosis. In the only other controlled isoxazoline field study, in Europe, dogs with generalized demodicosis were treated orally at monthly intervals with sarolaner at a dose rate of 2 – 4 mg/kg, or with imidacloprid-moxidectin as used in the current study [14]. At day 30, 15.1 and 17.9% of dogs treated with sarolaner or imidacloprid-moxidectin were mite-free, respectively. The study concluded 180 days after the first treatment, with up to 6 administrations of sarolaner producing a parasitological cure in all dogs that remained in the study, and up to 24 weekly doses of imidacloprid-moxidectin producing a parasitological cure in 91.7% of the remaining dogs in that group.
In an uncontrolled study in Europe, two formulations of afoxolaner for oral administration, one as a single entity product, the other in combination with milbemycin oxime, were administered on days 0, 28, and 56 to dogs presenting with generalized demodicosis [15]. Although mite counts were reduced from pre-treatment levels by 87.6% on day 28 and by 98.1% on day 84, just 29 of 48 (60.4%) dogs were mite free on day 56, so the maximum possible cure rate (two consecutive assessments in which dogs were mite free) following those three treatments would be 39.6%.
In another uncontrolled field study, in Thailand, a parasitological cure was observed in 100% of dogs (n = 67) within 3 months following treatment with orally administered fluralaner [16]. An extended duration of follow up found that 4 of 46 successfully treated adult-onset dogs had relapsed at 2, 7, 10, or 12 months following cure. The possibility of relapse, as long as 12 months after successful treatment, emphasizes the need for extended post-cure vigilance, particularly of older dogs, in which a cure has been realized.
Six laboratory studies, all from a single facility in South Africa, have shown the potential of each of the isoxazolines in the treatment of canine generalized demodicosis [10 - 13, 17, 23]. Three consecutive treatments at 4-weekly or monthly intervals were used in separate studies of sarolaner [11] and afoxolaner [12], and in an uncontrolled study with lotilaner [13]. Two studies, one uncontrolled, investigated single-treatment fluralaner efficacy using the chewable formulation [10, 23], and one controlled study involved the spot-on formulation [17]. The multiple treatments with afoxolaner, sarolaner, and lotilaner, and the single treatment controlled study with either fluralaner formulation, all reduced mean demodectic mite counts by >99% within the month following the day 0 treatment, and by 100% at days 81 or 84. Across those studies, the reported efficacies of imidacloprid-moxidectin within the month after the first treatment ranged from 9.8 to 89.8%, and on day 84, following multiple treatments, from 0 to 100%. In the uncontrolled oral fluralaner study, PCR analysis of hair collected from treated dogs found that Demodex DNA levels progressively declined throughout the study, and on day 112 were reduced 1000-fold from pre-treatment levels [23]. Thus, the accumulating data in which the isoxazolines have shown potent efficacy and superiority over imidacloprid-moxidectin indicate that they would be the treatment of choice for generalized demodicosis, although further controlled studies would be helpful to confirm that the miticidal efficacy of afoxolaner and lotilaner is maintained under field conditions.
Regardless of the efficacy of these products, generalized demodicosis, particularly in older dogs, becomes clinically apparent in those affected by another disease process, or by immunosuppressive therapy, factors which can also predispose successfully treated dogs to a relapse [2, 5, 16]. A corollary of that risk of relapse is the requirement for continued vigilance of cured dogs, and the associated potential need for repeated miticidal treatments over an extended period. In this regard, the long efficacy duration of fluralaner has been linked to better owner adherence compared with use of monthly treatments [24]. The sustained action and convenience of fluralaner formulations could also help to improve the long-term cure rate of dogs with generalized demodicosis.