Search

Background: From three days following host attachment, the Australian paralysis tick, Ixodes holocyclus, secretes a neurotoxin that annually causes paralysis in approximately 10,000 domestic pets. Lotilaner, a novel isoxazoline formulated in a chewable flavoured tablet (Credelio TM ), produces rapid onset of acaricidal activity in dogs, with an efficacy duration of at least one month. Two studies were performed to determine the efficacy of lotilaner against I. holocyclus infestations over 3 months., Methods: Both studies included 16 dogs, ranked according to I. holocyclus counts on Day -5 (from infestations on Day -8) and blocked into pairs. One dog in each pair was randomized to be a sham-treated control, the other to receive lotilaner at a minimum dose rate of 20 mg/kg on Day 0. Dogs were dosed in a fed state. Infestations were performed in both studies on Days -8 (to determine the tick carrying capacity of each dog) -1, 28, 56, 70, 77 and 84, and additionally in Study 1 on Day 91, in Study 2 on Days 14 and 42. In Study 1, ticks were counted and assessed as alive or dead at 24, 48 and 72 h post-initial infestation and post-subsequent re-infestations. In study 2, ticks were counted at 24, 48 and 72 h post-dosing or post-re-infestation. Efficacy was determined by the percent reduction in live attached tick counts in the lotilaner group compared to control., Results: Within 48 h post-treatment in Study 1 and within 72 h post-treatment in Study 2 all lotilaner-group dogs were free of live ticks. By 72 h post-infestation, efficacy in Study 1 remained at 100% through Day 87, except on Day 31 when a single tick was found on one dog, and through Day 59 in Study 2. Efficacy exceeded 95% through the final assessment in each study (Days 94 and 87 in Studies 1 and 2, respectively)., Conclusion: These results demonstrate that lotilaner quickly kills existing I. holocyclus infestations. By providing 95.3-100.0% protection through at least 87 days post-treatment, lotilaner can be a valuable tool in reducing the risk of tick paralysis in dogs.

Background: Throughout Japan, Korea and China, Haemaphysalis longicornis ticks are vectors of Babesia gibsoni, which causes severe and progressive anemia in dogs. This study evaluated the efficacy of a single administration of lotilaner flavored chewable tablets (Credelio TM ) against experimental canine H. longicornis infestations., Methods: Twenty-two healthy Beagles were ranked in descending order of counts of H. longicornis completed 48 h after challenge on Day -7. The 16 dogs with the highest live tick counts were blocked into pairs and within pairs randomized to either lotilaner-treatment at a minimum dose rate of 20 mg/kg or sham-treated controls. Treatment was administered within 30 ± 5 min following feeding on Day 0. Infestations with 50 unfed adult H. longicornis were completed on Days -2, 7, 14, 21, 28 and 35. Elizabethan collars were placed for 48 (± 2) h after each infestation and a T-shirt was placed on each dog to facilitate attachment. Ticks were counted in situ 12 and 24 h post-treatment and counted and removed after an additional 24 h (48 h after treatment) and 48 h after each post-treatment infestation. Dogs were sedated for tick challenges and counts. Live attached ticks on each dog were counted for efficacy assessments. Lotilaner was considered effective if the average tick attachment rate in the control group was at least 20%, if there was a statistically significant difference (P < 0.05) in mean tick counts between treated and control groups, and if the lotilaner-treated group had a calculated efficacy of at least 90%., Results: Average control group retention of the H. longicornis challenge exceeded 20% at each assessment. Lotilaner started killing H. longicornis ticks quickly, achieving 57.4% efficacy within 12 h. At 48 h post-treatment, and following each subsequent infestation, between-group differences in mean H. longicornis counts were significant (P < 0.0001). From 48 h post-treatment, through the final assessment on Day 37, lotilaner efficacy remained greater than 95%, including on Day 37 when efficacy was 98.4%., Conclusion: Lotilaner, administered to dogs orally at a minimum dose rate of 20 mg/kg is well tolerated, provides rapid reduction of existing H. longicornis tick infestations, and provides sustained residual protection for at least 35 days.

Background: Lotilaner is approved for dogs as a chewable tablet formulation. It has separately been developed for oral administration in cats (Credelio™ chewable tablets for cats) to meet the need for an easy to use, safe and rapidly effective parasiticide and as an alternative to topical products. This paper describes two pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ctenocephalides felis fleas following a single oral administration, at the minimum recommended dose rate of 6 mg/kg., Methods: Two GCP (Good Clinical Practice), blinded, randomized, negative-controlled, parallel-groups, laboratory studies were performed. In both studies, lotilaner was administered once, per os, at the minimum recommended dose of 6 mg/kg. Study 1 evaluated the efficacy of lotilaner tablets for cats against adult C. felis in experimentally infested cats, 24 h after treatment and after new weekly infestations, until day 35. Study 2 evaluated the speed of kill of lotilaner against C. felis, in cats, 8 and 12 h after treatment and after each subsequent weekly infestation, through day 35. In both studies, for each assessed time point, animals were randomized 1:1 to a lotilaner-treated or a contemporaneous negative control group of 8 cats each., Results: In both studies, the infestation in the control groups was adequate at all assessment times. In Study 1, efficacy at 24 h was 100% at all time points. In Study 2, efficacy was ≥ 97.4% at the 8 h and ≥ 98.6% at the 12 h time point, through one month. Lotilaner was well tolerated, with no product-related adverse events reported., Conclusions: Lotilaner administered orally to cats at the minimum recommended dose rate of 6 mg/kg was effective as early as 8 hours post-administration and at 8 hours after subsequent weekly infestations of adult C. felis for at least one month. The product was well-tolerated.

A fixed-dose combination tablet of benazepril and pimobendan (Fortekor Plus; Elanco Animal Health) was tested in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD) in a three-arm, masked, randomized, non-inferiority clinical trial in Japan. The test group (n = 34) received Fortekor Plus twice daily. Two control groups received registered formulations of benazepril (Fortekor; Elanco Animal Health) and pimobendan (Vetmedin; Boehringer Ingelheim Vetmedica) with administration of Vetmedin twice daily and Fortekor twice (Control I, n = 14) or once (Control II, n = 19) daily. Diuretics were used in 22 dogs (32.8%). Global clinical scores decreased significantly from baseline in all groups; there were no significant differences between groups, and non-inferiority of Fortekor Plus compared to Control I, Control II, and combined Control I + II groups was demonstrated. There were no significant differences between groups for relevant clinical chemistry and hematology variables or frequency of all adverse events. Frequency of emesis was significantly ( p = 0.0042) lower in the Fortekor Plus (8.8%) group than in the Control I + II (39.4%) group. In conclusion, Fortekor Plus had non-inferior efficacy and was associated with significantly less emesis compared to Fortekor and Vetmedin in dogs with CHF caused by MMVD.

Background: Oral administration of lotilaner flavoured chewable tablets (Credelio™, Elanco) to dogs has been shown to provide a rapid onset of killing activity of infesting ticks, with sustained efficacy for at least 35 days. A study was undertaken in Europe to confirm lotilaner's safety and anti-tick efficacy in client-owned dogs., Methods: In this assessor-blinded study, dogs were enrolled at 19 clinics in Germany, Hungary and Portugal. Qualifying households with no more than three dogs were randomized in an approximate 2:1 ratio to a lotilaner or fipronil/(S)-methoprene (FSM) (Frontline® Combo Spot-on, Merial) treatment group. One household dog with at least three live attached ticks was the primary dog. Treatments were dispensed Days 0, 28 (± 2) and 56 (± 2) for owner administration to all household dogs. Tick counts were performed on primary dogs Days 7 (± 1), and ±2 days on Days 14, 21, 28, 42, 56, 70 and 84; supplementary dogs were assessed for safety ± 2 days on Days 28, 56 and 84. Efficacy was assessed by comparing mean Day 0 live attached tick counts with subsequent counts., Results: The most frequently retrieved ticks were Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus (sensu lato), with Ixodes hexagonus also present. In the lotilaner group (n = 127) geometric mean tick count reductions were at least 98% from the first post-treatment visit (Day 7) through Day 56, when efficacy was 100%. For FSM (n = 68), efficacy remained at least 96% through Day 84, but at no point were all dogs free of live attached ticks. Mean counts in lotilaner-treated dogs were significantly lower than FSM-treated dogs on Days 7, 42, 70 and 84 (P < 0.05). Percent efficacy over all post-enrolment visits was 99.3 and 98.3% for lotilaner and FSM groups, respectively (t (190)  = 2.23, P = 0.0268). Owners successfully administered all treatments, and both products were well-tolerated., Conclusion: Under European field conditions, lotilaner flavoured chewable tablets administered monthly, were > 98% effective in eliminating live ticks from the first post-treatment assessment (Day 7) through Day 56 and maintained 100% of dogs tick-free on Days 70 and 84. Lotilaner was safe, providing superior tick control to FSM administered according to the same schedule.

Background: Lotilaner (Credelio™, Elanco), a novel isoxazoline, is a systemic insecticide and acaricide that is rapidly absorbed following oral administration to dogs and has a half-life of 30 days. As part of a development program, studies were undertaken to investigate lotilaner's initial and sustained efficacy and speed of kill against fleas., Methods: Four studies were conducted to evaluate the onset of lotilaner's speed of flea knockdown at the time of treatment, and to determine the sustained speed of flea kill (SOK) up to 35 days post-treatment. Each study assessed one or two specific time points (4, 6, 8 and 12 h) post-treatment and following weekly re-infestations. In each study, dogs were randomised to a lotilaner or an untreated group based on pre-administration flea counts, and before treatment were infested with adult Ctenocephalides felis. Dogs randomised to a lotilaner group received a single treatment on Day 0, at the minimum recommended dose rate of 20 mg/kg, 30 (± 5) minutes after being fed. Efficacy was calculated using geometric, and arithmetic mean flea counts in treated versus untreated groups., Results: On Day 0, lotilaner efficacy was 89.9% at 4 h, 99.2% at 6 h, 99.9% at 8 h, and 100% at 12 h post-treatment. At each weekly assessment, lotilaner efficacy at 4 h remained at > 97%, at 8 h remained at > 99%, and at 12 h remained at 100% through Day 35. Across all studies, there were no treatment-related adverse events., Conclusion: Lotilaner's rapid flea knockdown immediately following treatment and sustained SOK through 35 days post-treatment offers a new solution for helping to eliminate the health risks that accompany flea infestations on dogs. The consistency of the rapid, sustained flea SOK demonstrated in these studies generates confidence that monthly use of lotilaner in dogs can be valuable in disrupting the flea life cycle in a contaminated environment, and that newly acquired fleas will die quickly, thereby reducing the discomfort of flea bites. The sustained lotilaner SOK also provides confidence that there will be no "end-of-dose" resurgence in flea burdens with the potential accompanying consequence of flares in flea-bite hypersensitivity.

Background: There is a continuing need for novel approaches to tick control in dogs. One such approach lies in the ability of lotilaner (Credelio™), an isoxazoline with a rapid onset of action, to provide sustained efficacy against ticks. Two studies were undertaken to confirm lotilaner's efficacy, at the minimum dose rate of 20 mg/kg, against the three most common tick species in Europe., Methods: In each of two studies, 16 Beagle dogs, at least 6 months old, were ranked and blocked by tick counts from infestations placed approximately 1 week before treatment. Within blocks, dogs were randomized to receive either lotilaner flavoured chewable tablets at as close as possible to, but not less than the minimum dose rate of 20 mg/kg, or to be sham-treated controls. Study 1 assessed lotilaner efficacy against concurrent infestations with 50 (± 6) Rhipicephalus sanguineus and 70 (± 6) Ixodes ricinus; Study 2 infestations were with 50 (± 2) Dermacentor reticulatus. Infestations were performed on Day -2 with counts on Day 2, 48 (± 2) hours post-treatment. Post-treatment infestations were performed on Days 7, 14, 21, 28 and 35, and ticks were counted 48 (±2) hours post-infestations. Efficacy was determined by the percent reduction in mean live tick counts., Results: Control group infestations for each tick species were adequate for assessing lotilaner efficacy at all assessment times. On Day 2 no live ticks were found on any lotilaner-treated dog. For subsequent counts, in Study 1 lotilaner was 100% effective in eliminating live I. ricinus and R. sanguineus on all but two occasions for each tick; on each of those occasions efficacy was sustained at greater than 98.0%. In Study 2, except for a single unattached live tick found on Day 16, efficacy against D. reticulatus was 100% at every post-treatment assessment., Conclusion: The high and sustained efficacy against the three common species of ticks in Europe, R. sanguineus, I. ricinus and D. reticulatus, demonstrates that lotilaner can be a valuable tool in the treatment of canine tick infestations. Lotilaner flavoured chewable tablets were well tolerated and effectiveness was sustained through at least 35 days.

Background: Dogs worldwide are at risk of Babesia spp. infections. Preventive efficacy of lotilaner tablets (Credelio™, Elanco) against Babesia canis was evaluated in two studies., Methods: Sixteen dogs in Study 1 and 12 dogs in Study 2, all seronegative and polymerase chain reaction (PCR) negative for B. canis, were randomized to a sham-treated control group or a lotilaner (20-43 mg/kg) treatment group, administered on Day 0 (Study 1: n = 8/group; Study 2: n = 6/group). Dogs were each infested with 50 Dermacentor reticulatus, a percentage of which (Study 1: 8.0-30.0%; Study 2: 12.2%) were infected with B. canis, in Study 1 on Days 2, 7, 14, 21 and 28, and in Study 2 on Day 28. Ticks were removed and counted on Day 30 in Study 1, and Day 34 in Study 2. Blood was collected for Babesia detection via smear, PCR and immunofluorescence assay (IFA) in Study 1 on Day 2, then approximately weekly through Day 56, and in Study 2 at weekly intervals between Days 28 to 49, and on Days 63 and 91. Additional samples were collected from dogs with body temperature > 39.4 °C (measured three times weekly, from Days 7 to 56 in Study 1 and from Days 35 to 56 in Study 2) and positive for B. canis on blood smear. Dogs with confirmed infections were rescue-treated, removed from the study and, in Study 1, replaced., Results: Across both studies B. canis infection of ticks ranged between 8.0-30.0%. In Study 1, all control dogs were positive for B. canis on blood smear and PCR on Day 10 and IFA on Day 21; on Day 21 seven of eight replacement control dogs were B. canis-positive; no replacement dogs were B. canis-positive following tick removal on Day 30. In Study 2, all control dogs were B. canis-positive on Day 56. All lotilaner-treated dogs remained B. canis-negative at all assessments in both studies., Conclusion: Lotilaner efficacy was 100% in preventing establishment of B. canis infection, despite post-treatment challenge with infected ticks on Days 2, 7, 14, 21 and 28.

Background: With the geographical expansion of tick species and increased recognition of pathogens they transmit, there is a requirement for safe and rapidly effective control measures for dogs. Lotilaner, a novel isoxazoline, is rapidly absorbed following administration of a flavored chewable tablet formulation (Credelio™), providing at least 98% efficacy for at least 1 month following assessments at 48 h post-treatment, and following subsequent challenges. A study was conducted to determine the speed with which lotilaner kills ticks., Methods: From 38 dogs, the 32 with the highest Ixodes ricinus counts from a Day -4 infestation were randomized among four groups: two groups were untreated controls, two received lotilaner tablets at a minimum dose rate of 20 mg/kg. Infestations with I. ricinus were performed on Days -2, 7, 14, 21, 28 and 35. Counts were completed 4 and 8 h post-treatment (Day 0), and 8 and 12 h following subsequent infestations. All live ticks were incubated for 24 h following removal from study dogs., Results: At 4 h post-treatment, there was a 69.8% reduction in geometric mean live tick counts in treated dogs compared to controls. After incubation, the reduction increased to 97.2%. At 8 h after treatment, pre- and post-incubation reductions were 99.2 and 100%, respectively. Following post-treatment challenges, post-incubation efficacy through Day 28 at 8 and 12 h was at least 94.3 and 98.0%, respectively, and was 85.7 and 94.2% at 8 and 12 h after the Day 35 challenge. Mean live tick counts in the lotilaner groups were significantly lower than in the control groups at all assessments through Day 35 at 8 (t (7)  ≥ 9, P < 0.0001, Days 0 to 28; t (7)  = 3.54, P ≤ 0.0095, Day 35) and 12 h post-treatment and after subsequent infestations (t (7)  ≥ 10, P < 0.0001, all days). There were no treatment-related adverse events., Conclusion: Lotilaner at a minimum dose rate of 20 mg/kg began to kill ticks on dogs within 4 h of treatment and efficacy was 100% within 8 h. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest dogs, lotilaner has potential to help limit the transmission of tick-borne pathogens.

Background: Effective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens. Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States., Methods: Eight studies investigated the efficacy of lotilaner against ticks. In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species. Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis. In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20 mg/kg), or to be untreated controls. Treatments were administered on Day 0, within 30 min after dogs were fed. In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis. Tick counts were completed 48 h after treatment or after each subsequent challenge. An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation. Efficacy calculations for the primary objective were based on geometric means., Results: In all studies, lotilaner was 100% effective against existing infestations. For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%. Only mild and transient adverse events were observed, and none were considered to be related to treatment., Conclusion: Lotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.

Background: Lotilaner (Credelio™) is the newest member of the novel isoxazoline chemical class to be developed to treat canine ectoparasitism. Administered orally, lotilaner is rapidly absorbed with peak blood levels occurring within 2 h post-treatment. A study was undertaken to determine the earliest onset of lotilaner's efficacy against existing flea infestations., Methods: From 72 Beagles, 64 qualifying dogs were ranked in descending order of flea counts from a Day -8 infestation and placed into eight blocks. Within blocks, eight dogs were randomly allocated among eight groups: Groups 1 to 4 were treated orally with lotilaner, at as close as possible to the minimum dose rate of 20 mg/kg within 30 (± 5) minutes after feeding; Groups 5 to 8 were untreated controls. All dogs were infested with 100 ± 5 fleas on Day -2, and whole-body flea counts were completed at 30 min and one, two and 8 h after treatment. Efficacy calculations were based on arithmetic and geometric means if an adequate infestation (at least six of eight untreated dogs with a flea retention of ≥ 50%) was demonstrated in the equivalent control group., Results: Adequate infestations were established in all control groups. At 30 min and 1 h post-treatment, relative to the matching untreated control group, there were no significant reductions in mean flea counts in lotilaner-treated dogs, although moribund fleas were evident at 1 h post-treatment. At 2 h after treatment, compared with the equivalent control group, the geometric mean flea count reduction in the lotilaner group was 64.0% (t (7)  = 2.86, P = 0.0242). At 8 h after treatment, lotilaner efficacy was 99.6%. There were no treatment-related adverse events., Conclusion: This study demonstrates that lotilaner flavored chewable tablets are well tolerated and begin to kill fleas within 2 h of treatment, achieving 99.6% efficacy within 8 h. Lotilaner can therefore be used to quickly alleviate the flea irritation that arises from existing infestations.

Background: Chronic kidney disease (CKD) is an important cause of morbidity and mortality in dogs., Objective: To evaluate the efficacy in prolonging survival and safety of benazepril administration to dogs with CKD., Animals: Forty-nine client-owned dogs with CKD., Methods: Dogs were randomized to benazepril (0.25 to <0.5 mg/kg) or placebo once daily for up to 2 years in a prospective, multicenter, blinded clinical trial. The primary endpoint variable was the renal survival time, defined as the time from inclusion in the study to the treatment failure endpoint of death or euthanasia or need for administration of parenteral fluids related to renal failure., Results: No benefit of benazepril versus placebo was detected for renal survival time in all dogs; median (95% confidence interval (CI)) survival times were 305 (53-575) days in the benazepril group and 287 (152-not available) in the placebo group (P = .53). Renal survival times were not significantly longer with benazepril compared to placebo for subgroups: hazard ratios (95% CI) were 0.50 (0.21-1.22) with P = .12 for initial urine protein-to-creatinine ratio (UPC) >0.5, and 0.38 (0.12-1.19) with P = .080 for initial UPC >0.5 plus plasma creatinine ≤440 μmol/L. Proteinuria, assessed from the UPC, was significantly (P = .0032) lower after treatment with benazepril compared to placebo. There were no significant differences between groups for clinical signs or frequencies of adverse events., Conclusions and Clinical Relevance: Benazepril significantly reduced proteinuria in dogs with CKD. Insufficient numbers of dogs were recruited to allow conclusions on survival time., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The objective of the study was to establish the dose-response relationship for robenacoxib, a selective cyclooxygenase (COX)-2 inhibitor, in a urate crystal model of acute synovitis. In a randomized partial Latin square design trial, 12 beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4 and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after injection of sodium urate crystals into a stifle joint. Dogs were assessed for weight bearing on a force plate and by subjective clinical orthopaedic observations. Robenacoxib produced dose-dependent improvement in weight bearing, and decreased pain on palpation and joint swelling, over the dose range 0.5-2 mg/kg with no further increase in effect over the range 2-8 mg/kg. For weight bearing on the force plate, the ED 50 of robenacoxib was 0.6-0.8 mg/kg. The onset of action and time to peak effect of robenacoxib were faster (respectively, 2-2.5 h and 3-5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib significantly inhibited COX-2 at all doses, with dose-related activity. Robenacoxib did not inhibit COX-1 over the dose range 0.5-4 mg/kg, but produced transient inhibition at 8 mg/kg. In conclusion, oral administration of robenacoxib over the dose range 0.5-8 mg/kg demonstrated significant analgesic and anti-inflammatory efficacy in dogs., (© 2016 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.)

Background: In Canada, surveys of enteric parasites in dogs and cats have been reported sporadically over the past 40 years, mostly focusing on a specific region. The present work was performed to determine the current prevalence of various parasites in fecal samples from shelter dogs and cats across the Canadian provinces., Methods: A total of 1086 dog and 636 cat fecal samples from 26 shelters were analysed using a sugar solution double centrifugal flotation technique. Prevalences (national, regional, provincial, age and parasite-specific), were calculated and compared using the Fisher-Exact test. A multiplex PCR was performed to distinguish Taenia spp, Echinococcus granulosus and E. multilocularis on samples positive for taeniid eggs., Results: Overall, 33.9% of dogs and 31.8% of cats were positive for at least one parasite. Toxocara canis and T. cati were the most prevalent parasite present in fecal samples followed by Cystoisospora spp. Prevalence in dogs was similar across the Atlantic, East, West and Pacific regions, while prevalence in cats varied regionally. Eggs of E. granulosus/E. canadensis were detected in samples from dogs from BC, AB, and ON., Conclusions: Data from this study will help in the development of strategies, based on the level of risk per geographic location for the prevention and response to these parasites in pets and free-roaming and shelter animals in Canada.

Background: We developed a canine model of acute atopic dermatitis to evaluate the potential of compounds to treat pruritus and skin lesions induced in Dermatophagoides farinae (Df)-sensitized dogs., Hypothesis/objectives: The aim was to investigate the effectiveness of long-term recording activity monitors to assess pruritus induced by allergen challenges., Animals: Thirty-two Df-sensitized laboratory dogs., Methods: In two blinded crossover studies, 28 Df-sensitized dogs were challenged on 3 days with a Df slurry applied to clipped abdominal skin. Dogs were treated with a positive control (prednisolone 1 mg/kg once daily for 5 days, starting 1 day before challenge) or left untreated; all were fitted with activity monitors. To confirm pruritus, a parallel study with four dogs was conducted, filming the dogs before and during challenge and assessing the film for pruritic behaviour., Results: The activity of dogs treated with prednisolone was significantly lower between 00.00 and 03.00 h and between 03.00 and 06.00 h compared with untreated dogs (repeated-measures ANCOVA; P < 0.0001). To determine whether the recorded night-time activity corresponded to pruritic manifestations, we compared activity monitor and video recordings of four dogs for two periods (16.30-20.30 and 24.00-03.00 h) before and during a Df challenge. The correlation between night-time activity monitor activity and observed pruritic behaviour was highly significant (test of correlation coefficient versus zero: r = 0.57, P < 0.0001)., Conclusions and Clinical Importance: Determination of night-time activity with activity monitors after allergen challenge appears to be an objective and practical way to assess pruritus in this experimental model of canine atopic dermatitis., (© 2014 ESVD and ACVD.)

Crenosoma vulpis, the fox lungworm, infects wild and domestic canids and is a cause of chronic respiratory disease in dogs in North America and Europe. The objective of this study was to determine the efficacy of milbemycin oxime (0.5mg/kg)/praziquantel (5mg/kg) (Milbemax; Novartis Animal Health, Inc.) against C. vulpis infection in a randomized, blinded, placebo-controlled study using experimentally infected dogs. Sixteen beagles (8 males, 8 females) were each given 100 infective third-stage larvae of C. vulpis. Fecal samples were examined for first-stage larvae by quantitative Baermann examination pre-exposure and at days 21, 28, 35, 42 and 49 post-infection (PI). All of the dogs were shedding larvae in the feces at 21 days PI. The dogs were randomly assigned to one of two groups. At 28 days PI, Group 1 (4 males, 4 females) received placebo only while Group 2 (4 males, 4 females) received a single treatment of milbemycin oxime (0.5mg/kg) and praziquantel (5mg/kg). The 16 dogs were euthanized and necropsied at 49 days PI. Lungs were removed, assessed for gross lesions (graded on a subjective scale 0-3 with 0 being normal) and C. vulpis were collected by lung-flush and counted. Samples of lung tissue were preserved for evaluation of histopathology and the lesions graded on a subjective scale (0-3 with 0 being normal). Gross and histopathology lesions were detected in all 8 untreated Group 1 dogs with mean subjective lesion scores of 1.8 ± 0.7 (range 1-3) and 3.0 ± 0.0 (range 3), respectively. Gross lesions were observed in 3/8 and histopathology lesions in all 8 of the treated Group 2 dogs with mean subjective lesion scores of 0.4 ± 0.5 (range 0-1) and 1.3 ± 0.4 (range 1-2), respectively. The mean (geometric) number for adult C. vulpis recovered in untreated dogs was 48.3 (range 25-70) compared with 0.65 (range 0-2) in animals treated with Milbemax. The resulting efficacy against C. vulpis was 98.7%. The number of C. vulpis was significantly lower for treated dogs than the burden in the untreated group (p=0.0002). A single dose of Milbemax (milbemycin oxime 0.5mg/kg+praziquantel 5mg/kg) was highly effective for the treatment of patent C. vulpis infection in dogs. A dosing interval for the prevention of clinical disease in dogs exposed to natural infections has not been established., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The efficacy and tolerability of robenacoxib for the treatment of osteoarthritis in dogs were evaluated in a prospective, multicenter, randomized, noninferiority design clinical trial. A total of 32 dogs presenting with osteoarthritis were allocated randomly to receive, orally once daily for 28 days, either 1-2 mg/kg robenacoxib (n=21) or 3.5-5 mg/kg carprofen (n=11). Dogs were assessed by clinicians and owners using numerical rating scale scores at baseline and days 14 and 28. The primary efficacy endpoint was the global functional disability score, which was the sum of clinician scores for standing posture, lameness at walk, lameness at trot, willingness to raise the contralateral limb and pain at palpation. There was a good to excellent level of efficacy in both treatment groups. Differences between days 14 and 28 compared to day 0 were significant for all 11 clinician and owner scores for robenacoxib, and for 6 of 11 scores for carprofen. The efficacy of robenacoxib was numerically superior to carprofen for all 13 endpoints, but differences were not statistically significant. For the global functional disability score, the estimated efficacy of robenacoxib was 1.244 (95% confidence interval 0.555-2.493) relative to carprofen. The tolerability of both treatments was good as assessed from adverse events, clinical signs, and hematology and serum biochemistry variables. In conclusion, once daily administration of robenacoxib tablets had noninferior efficacy and tolerability compared to carprofen for the treatment of the clinical signs of osteoarthritis in dogs.

Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: robenacoxib at 1-2 mg/kg (n = 125 dogs) and racemic carprofen at 2-4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7-84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis., (© 2011 Blackwell Publishing Ltd.)

Objective: To assess efficacy and tolerability of robenacoxib for control of pain and inflammation in dogs undergoing orthopedic surgery., Animals: 140 client-owned dogs., Procedures: A multicenter, prospective, randomized, blinded field trial was conducted to compare robenacoxib (97 dogs) and meloxicam (43 dogs). After randomization, each dog received an initial dose (robenacoxib, 2 mg/kg; meloxicam, 0.2 mg/kg) via SC injection before surgery and daily doses (robenacoxib, 1 to 2 mg/kg; meloxicam, 0.1 mg/kg) administered orally for up to 15 days after surgery. Efficacy was assessed by veterinarians and owners via numeric rating scales and visual analogue scales. Safety was assessed on the basis of reported adverse events, clinical signs, results of hematologic and biochemical analyses, and buccal mucosa bleeding times., Results: Treatment groups were balanced with respect to baseline and demographic data. Both treatments provided similar adequate pain control, as assessed with a modified Glasgow pain scale as the primary end point and supported by secondary end points in evaluations conducted by veterinarians and owners. For the primary end point, the ratio of the reciprocal of the scores for robenacoxib to meloxicam was 1.16 (95% confidence interval, 0.98 to 1.37). No dogs required rescue analgesia. Both treatments were associated with only minor adverse events, which were not necessarily related to the administered treatments and did not affect mucosal bleeding times., Conclusions and Clinical Relevance: Robenacoxib provided efficacy and tolerability similar to those of meloxicam for the management of perioperative pain and inflammation in dogs undergoing orthopedic surgery.

Canine idiopathic sebaceous adenitis (ISA) is an inflammatory reaction of sebaceous glands, potentially resulting in their complete loss. It is considered a T-cell-mediated disease, but its precise pathogenesis is still unknown. Topical treatment with oil soaks, humectants and shampoos is effective but laborious. Ciclosporin A (CsA), an immunomodulatory drug, has recently been shown to ameliorate the clinical picture of ISA and to reduce inflammation greatly. It is, however, an expensive treatment option. The objective of this multicentre, partly double-blinded, randomized controlled study was to evaluate the efficacy of ciclosporin A, either alone or with topical therapy, in comparison to conventional topical treatment alone, as measured by the primary end-points alopecia and scaling, and multiple histopathological secondary objectives. Thirty-four dogs with an established diagnosis were treated for 4-6 months and were evaluated before, during and after therapy. Both CsA and topical therapy demonstrated efficacy in this study. Differences between the treatment protocols were marginal. Topical treatment, both alone and in combination with CsA, appeared to reduce scaling more effectively than CsA alone. Both therapies reduced alopecia. There is evidence of a synergistic benefit on both scaling and alopecia, if both treatment options are combined. Inflammation of the sebaceous glands is also best reduced by a combination of both CsA and topical therapy. There is evidence that regeneration of sebaceous glands is best achieved by CsA, either given alone or in combination with topical treatment., (© 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.)

The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.

Canine atopic dermatitis (CAD) is a multifaceted disease associated with exposure to various offending agents such as environmental and food allergens. The diagnosis of this condition is difficult because none of the typical signs are pathognomonic. Sets of criteria have been proposed but are mainly used to include dogs in clinical studies. The goals of the present study were to characterize the clinical features and signs of a large population of dogs with CAD, to identify which of these characteristics could be different in food-induced atopic dermatitis (FIAD) and non-food-induced atopic dermatitis (NFIAD) and to develop criteria for the diagnosis of this condition. Using simulated annealing, selected criteria were tested on a large and geographically widespread population of pruritic dogs. The study first described the signalment, history and clinical features of a large population of CAD dogs, compared FIAD and NFIAD dogs and confirmed that both conditions are clinically indistinguishable. Correlations of numerous clinical features with the diagnosis of CAD are subsequently calculated, and two sets of criteria associated with sensitivity and specificity ranging from 80% to 85% and from 79% to 85%, respectively, are proposed. It is finally demonstrated that these new sets of criteria provide better sensitivity and specificity, when compared to Willemse and Prélaud criteria. These criteria can be applied to both FIAD and NFIAD dogs.

Canine atopic dermatitis (cAD) is a common disease with a multifactorial aetiology associated with impaired immunoregulation. The immunopathogenesis has similarities to that of human atopic dermatitis. Clinical signs of allergic disease in humans and mice are reduced by administration of saprophytic mycobacteria that amplify regulatory cytokines and hence the effect of Mycobacterium vaccae on the clinical severity of cAD was investigated. Sixty-two dogs with cAD, selected according to strict criteria, were treated with a single intradermal injection and evaluated monthly for 3 months in a placebo-controlled double-blind clinical trial. Clinical severity was quantified using standardized scores and by owner assessment of pruritus. A single injection of a heat-killed suspension of M. vaccae was found to be well tolerated and effective in treating mild to moderate cases of cAD demonstrable for 3 months, but was insignificant in more severely affected dogs.

Objective: To evaluate effects of zoledronate on markers of bone metabolism in dogs after transection of the cranial cruciate ligament (CrCL)., Animals: 21 adult dogs., Procedure: Unilateral CrCL transection was performed arthroscopically. Dogs were allocated to 3 groups (control group, low-dose zoledronate [10 microg/kg, SC, q 90 d for 12 months], and high-dose zoledronate [25 microg/kg, SC, q 90 d for 12 months]). Serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BAP), and urine pyridinoline and deoxypyridinoline concentrations were measured at 0, 1, 3, 6, 9, and 12 months after surgery. Bone mineral density (BMD) was determined in the distal portion of the femur and proximal portion of the tibia via computed tomography at each time point. Data were analyzed by a repeated-measures ANOVA., Results: oledronate inhibited OC in the high-dose group at 9 and 12 months and at 12 months in the low-dose group, compared with the control group. High-dose zoledronate decreased BAP concentrations 3 and 9 months after surgery. In the control group, BMD was decreased in the femoral condyle and caudal tibial plateau. Zoledronate prevented significant BMD decreases starting 1 month after transection, compared with control dogs. In the caudomedial aspect of the tibial plateau, both zoledronate groups had significant increases in BMD after 3 months, compared with control dogs., Conclusions and Clinical Relevance: Zoledronate may reduce subchondral bone loss and effect markers of bone metabolism in dogs with experimentally induced instability of the stifle joint and subsequent development of osteoarthritis.

Objective: To determine efficacy and safety of cyclosporine in the treatment of atopic dermatitis among dogs in North America., Design: Randomized controlled (phase 1) and open-label (phase 2) trials., Animals: 268 dogs with atopic dermatitis., Procedure: In phase 1, dogs were randomly assigned to be treated with cyclosporine (5 mg/kg [2.3 mg/Ib], PO, q 24 h) or a placebo. In phase 2, all dogs were treated with cyclosporine for 16 weeks. Frequency of cyclosporine administration was decreased if dogs improved clinically., Results: At the end of phase 1, canine atopic dermatitis extent and severity index (CADESI) scores for dogs treated with cyclosporine were significantly lower than scores for control dogs. Percentage of dogs with severe pruritus decreased from 67% to 16% for the cyclosporine group but from 66% to only 61% for the control group. During phase 2, cyclosporine dosage was decreased to every-other-day administration in 39% of the dogs after 4 weeks. After 12 weeks, 22% of the dogs were treated twice weekly and 36% were treated every other day. After 16 weeks, CADESI score had decreased > 50% in 68% of the dogs and 47% of dogs had no or mild pruritus. The most frequent adverse reactions were gastrointestinal tract signs., Conclusions and Clinical Relevance: Results suggest that cyclosporine is efficacious for the treatment of atopic dermatitis in dogs and that frequency of cyclosporine administration can be reduced following an initial induction period. The drug was well tolerated.

Pyotraumatic dermatitis (hot spot) is a common clinical syndrome in dogs but there are few prospective scientific studies related to it. The aim of this study was to investigate correlations among clinical pyotraumatic dermatitis, histopathology of the lesions and possible predisposing causes. The relationship of these with breed, age, sex and location of lesion was assessed statistically. A clinical diagnosis of acute pyotraumatic dermatitis was made in 44 privately owned dogs. Males exceeded females (P = 0.0348) and lesions were more common in dogs aged 4 years or less (P < 0.0001). Lesions were most often seen on the cheek, neck and lateral thigh with a significant correlation between breed and site of lesion (P < 0.0001). In 31 cases a possible underlying cause was found or suspected. In contrast to previous studies, no otitis externa was recorded and the study was conducted in an area without endemic fleas. Fourteen breeds were represented of which Rottweiler, German shepherd dog and golden retriever were most common. There was no significant seasonal incidence and no correlation among site of lesion and cause, time of year, age or sex. Histopathologically, the dogs could be separated into four patterns by the presence or absence of eosinophils and/or folliculitis. Eosinophils have not previously been recorded in pyotraumatic dermatitis but were seen in 29 cases. Acute folliculitis was seen in 20 cases. However, no correlation was seen among age, sex, breed, underlying cause or site of lesion and histopathology. Twenty-seven cases were cultured for bacteria of which 25 grew Staphylococcus intermedius and two were negative.

Objective: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy., Animals: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses., Procedure: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration., Results: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups., Conclusions and Clinical Relevance: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

The objective of this study was to compare the efficacy of oral ketoconazole and terbinafine for reducing population sizes of Malassezia yeasts on canine skin. Twenty-one Basset Hounds were randomised in three groups of seven according to Malassezia populations. Dogs in the first group were treated by oral administration of ketoconazole (Ketofungol) 200 mg, Janssen-Cilag) at 10 mg x kg-1, every 24 h with food, for 3 weeks. Dogs in the second group were treated by oral administration of terbinafine (Lamisil) 250 mg, Novartis) at 30 mg x kg-1, every 24 h with food, for 3 weeks. The seven remaining dogs were used as controls. Malassezia population sizes were assessed by use of contact plates on four cutaneous sites at days 7, 14 and 21. Both ketoconazole and terbinafine were effective in reducing the baseline levels of Malassezia organisms with no significant difference between the two drugs. In further studies, oral terbinafine should be evaluated for the management of canine cases of Malassezia dermatitis.

Cytological examination using the tape-strip technique and fungal culture using contact plates with modified Dixon's medium were compared to evaluate the carriage of Malassezia yeasts on four cutaneous sites (left pinna, umbilical region, axilla and perianal area) in adult Basset Hounds. Twenty animals were included in the study. High numbers of Malassezia were isolated from at least one area in 100% of the animals. The frequencies of isolation and population sizes differed significantly according to anatomical location. They were greater on the pinna, followed by the umbilical area, axilla and perianal area. Fungal culture was more sensitive than cytology for the isolation of Malassezia yeasts. Frequencies of isolation were greater using this method, but population sizes were constantly smaller than with cytology.

Objective: To evaluate a model for atopic dermatitis (AD) and to measure the effect of sensitization in Beagles genetically predisposed to produce high serum concentrations of allergen specific IgE., Animals: 22 laboratory Beagles., Procedure: Seventeen dogs were sensitized from birth to 3 allergens (recombinant birch pollen, Dermatophagoides pteronyssinus, and D farinae). Five nonsensitized dogs from the same litters served as controls. Clinical scoring, regular intradermal testing, measurement of serum concentrations of allergen-specific IgE, and collection of biopsy specimens of skin at 23, 32, and 43 weeks of age were performed. Serial tissue sections were stained for identification of IgE+ cells, mast cells and their subtypes, T-cells, Langerhans cells, and major histocompatibility complex class-II+ cells. At the age of 15 months, dogs were continuously exposed to 2 microg of mite allergen/g of dust., Results: Sensitized dogs had positive intradermal test reactions and significantly higher serum concentrations of allergen specific IgE, compared with nonsensitized dogs. In sensitized and nonsensitized dogs, a significantly higher number of mast cells was found at predilection sites, compared with the control biopsy site. The number of mast cells at predilection sites increased with age. Sensitization significantly increased the number of epidermal Langerhans cells by 23 weeks of age. The number of epidermal Langerhans cells significantly increased in nonsensitized dogs by 32 weeks of age. Clinical scoring only revealed mild transient erythema in some dogs., Conclusions: increases in concentrations of serum allergen-specific IgE and exposure to allergens is not sufficient to induce clinical signs of AD in genetically predisposed dogs.