Novel Virtual Reality App for Training Patients on MRI-guided Radiation Therapy.

Purpose: Patients receiving respiratory gated magnetic resonance imaging-guided radiation therapy (MRIgRT) for abdominal targets must hold their breath for ≥25 seconds at a time. Virtual reality (VR) has shown promise for improving patient education and experience for diagnostic MRI scan acquisition. We aimed to develop and pilot-test the first VR app to educate, train, and reduce anxiety and discomfort in patients preparing to receive MRIgRT. Methods and Materials: A multidisciplinary team iteratively developed a new VR app with patient input. The app begins with minigames to help orient patients to using the VR device and to train patients on breath-holding. Next, app users are introduced to the MRI linear accelerator vault and practice breath-holding during MRIgRT. In this quality improvement project, clinic personnel and MRIgRT-eligible patients with pancreatic cancer tested the VR app for feasibility, acceptability, and potential efficacy for training patients on using breath-holding during MRIgRT. Results: The new VR app experience was tested by 19 patients and 67 clinic personnel. The experience was completed on average in 18.6 minutes (SD = 5.4) by patients and in 14.9 (SD = 3.5) minutes by clinic personnel. Patients reported the app was "extremely helpful" (58%) or "very helpful" (32%) for learning breath-holding used in MRIgRT and "extremely helpful" (28%) or "very helpful (50%) for reducing anxiety. Patients and clinic personnel also provided qualitative feedback on improving future versions of the VR app. Conclusion: The VR app was feasible and acceptable for training patients on breath-holding for MRIgRT. Patients eligible for MRIgRT for pancreatic cancer and clinic personnel reported on future improvements to the app to enhance its usability and efficacy.

Clinical Application of Computational Methods in Precision Oncology: A Review.

Importance: There is an enormous and growing amount of data available from individual cancer cases, which makes the work of clinical oncologists more demanding. This data challenge has attracted engineers to create software that aims to improve cancer diagnosis or treatment. However, the move to use computers in the oncology clinic for diagnosis or treatment has led to instances of premature or inappropriate use of computational predictive systems. Objective: To evaluate best practices for developing and assessing the clinical utility of predictive computational methods in oncology. Evidence Review: The National Cancer Policy Forum and the Board on Mathematical Sciences and Analytics at the National Academies of Sciences, Engineering, and Medicine hosted a workshop to examine the use of multidimensional data derived from patients with cancer and the computational methods used to analyze these data. The workshop convened diverse stakeholders and experts, including computer scientists, oncology clinicians, statisticians, patient advocates, industry leaders, ethicists, leaders of health systems (academic and community based), private and public health insurance carriers, federal agencies, and regulatory authorities. Key characteristics for successful computational oncology were considered in 3 thematic areas: (1) data quality, completeness, sharing, and privacy; (2) computational methods for analysis, interpretation, and use of oncology data; and (3) clinical infrastructure and expertise for best use of computational precision oncology. Findings: Quality control was found to be essential across all stages, from data collection to data processing, management, and use. Collecting a standardized parsimonious data set at every cancer diagnosis and restaging could enhance reliability and completeness of clinical data for precision oncology. Data completeness refers to key data elements such as information about cancer diagnosis, treatment, and outcomes, while data quality depends on whether appropriate variables have been measured in valid and reliable ways. Collecting data from diverse populations can reduce the risk of creating invalid and biased algorithms. Computational systems that aid clinicians should be classified as software as a medical device and thus regulated according to the potential risk posed. To facilitate appropriate use of computational methods that interpret high-dimensional data in oncology, treating physicians need access to multidisciplinary teams with broad expertise and deep training among a subset of clinical oncology fellows in clinical informatics. Conclusions and Relevance: Workshop discussions suggested best practices in demonstrating the clinical utility of predictive computational methods for diagnosing or treating cancer.

Laboratory evaluation of the efficacy of lotilaner (Credelio™) against Amblyomma cajennense (sensu lato) infestations of dogs.

BACKGROUND: The ixodid tick Amblyomma cajennense (sensu lato) complex, widespread throughout South and Central America, is also present in Mexico, Texas and Florida. As a vector of Rickettsia rickettsii, and potentially of other pathogens, infestations with A. cajennense present a substantial health risk to humans, dogs and other mammals. Oral administration of lotilaner flavored chewable tablets (CredelioTM, Elanco) to dogs was previously shown to rapidly provide killing activity of infesting ticks. This study investigated lotilaner's efficacy against A. cajennense (s.l.). METHODS: Twenty purpose-bred Beagles (10 male and 10 female) were ranked by Day -5 burdens of nymphal A. cajennense (s.l.) and randomized to either treatment with lotilaner or to a sham-treated control group. On Day 0, dogs were fed within approximately 30 min prior to oral lotilaner administration at as close as possible to 20 mg/kg, the minimum dose rate. For efficacy assessments, tick counts were completed 48 h post-treatment or 48 h after experimental challenge infestations with 200 nymphal A. cajennense (s.l.) on Days -7, -2, 7, 14, 21 and 28. RESULTS: Tick infestations in the control group dogs ranged from a low of 43 to 95, with the average infestation remaining above 25% at each assessment, thereby meeting the requirement for efficacy comparison with the treated group. Lotilaner efficacy was 100% within 48 h post-treatment, and at nine days post-treatment. Efficacy was greater than 99% at all subsequent assessments through Day 30. No treatment-related adverse events were observed. CONCLUSION: The results demonstrate that lotilaner, administered orally to dogs at a minimum dose of 20 mg/kg is well tolerated, provides rapid reduction of existing A. cajennense (s.l.) tick infestations, and provides sustained residual protection for at least 30 days against subsequent infestation by A. cajennense (s.l.).

Laboratory evaluation of the efficacy of lotilaner (Credelio™) against Haemaphysalis longicornis infestations of 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 (CredelioTM) 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.

Laboratory evaluations of the 3-month efficacy of oral lotilaner (Credelio™) against experimental infestations of dogs with the Australian paralysis tick, Ixodes holocyclus.

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 (CredelioTM), 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.

Laboratory evaluation of the efficacy and speed of kill of lotilaner (Credelio™) against Ctenocephalides felis on cats.

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.

Laboratory evaluation of the efficacy and speed of kill of lotilaner (CredelioTM) against Ixodes ricinus ticks on cats.

BACKGROUND: Lotilaner, approved for dogs as a chewable tablet formulation, has separately been developed for oral use in cats (CredelioTM chewable tablets for cats), to meet the need for an easy to use, safe and rapidly effective parasiticide. It is a valid cat- and owner-friendly alternative to topical products. This manuscript describes three pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ixodes ricinus ticks following a single oral administration, at a dose rate close to 6 mg/kg. METHODS: In Studies 1 and 2, efficacy and safety were evaluated 48 h after treatment and post-treatment weekly infestations in 16 cats, against untreated controls, for 35 days. In Study 3, efficacy and safety were assessed in 8 lotilaner-treated cats until Day 35, before and after 24 h incubation of the female live ticks removed from the animals 12, 18 and 24 h after dosing and subsequent weekly infestations. RESULTS: Efficacy was > 99% on days 23 and 37, and 100% on all other timepoints in Study 1. In Study 2 it was > 98% on Days 9 and 37, and 100% on all other days. In Study 3, on Day 0, lotilaner was > 90% efficacious, pre- and post-incubation at all time-points. On Day 7, at 12 hours after infestation, efficacy was 100%, pre- and post-incubation. On Day 14, there was a 66.5% reduction in geometric mean live tick counts in treated cats compared to controls, increasing, after incubation, to 94.4%. Afterwards, efficacy decreased below 90% while tick counts in the treated groups remained significantly lower compared to controls. At 18 hours, lotilaner was ≥ 90% efficacious through Day 37, increasing to 100% at 24 hours, on all study days, with the exception of Day 28 (98.9 and 99.1% pre- and post-incubation, respectively). There were no treatment-related adverse events. CONCLUSIONS: At the minimum dose rate of 6 mg/kg, lotilaner was efficacious against I. ricinus ticks. In addition, lotilaner was effective against this tick within 12 hours of treatment, reaching 100% efficacy within 24 hours. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest cats, lotilaner has the potential to contribute to the reduction of tick-borne pathogens transmission.

A randomized, controlled field study to assess the efficacy and safety of lotilaner (Credelio™) in controlling fleas in client-owned cats in Europe.

BACKGROUND: Lotilaner is a new isoxazoline developed as an oral ectoparasiticide for cats and dogs. Its safety, rapid killing onset of action and sustained speed of fleas and ticks kill for a minimum of one month after administration, were demonstrated in a number of laboratory studies in cats. This study was performed to demonstrate the efficacy and safety of lotilaner flavored chewable tablets for cats (Credelio™, Elanco) in controlling fleas under field conditions in European countries. METHODS: Seventeen veterinary practices in France and Spain, located in high flea prevalence regions, participated in the study. Households with a maximum of three cats and two dogs were randomized 2:1 to a lotilaner (minimum dose rate 6 mg/kg) or a topical fipronil/(S)-methoprene combination (Frontline Combo® Spot-on Cats, Merial) group (administered according to label). In each household, efficacy against fleas and flea allergy dermatitis (FAD) signs were assessed in one primary cat (bearing a minimum of five fleas on Day 0) while safety was evaluated in all cats. There were 121 households included in the lotilaner and 61 in the fipronil/(S)-methoprene groups, respectively. Treatments were administered by the cats' owners on Day 0. Flea counts and FAD assessments were made on Days 0, 14, and 28. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus baseline pre-treatment counts. RESULTS: Lotilaner efficacy was 97.2 and 98.1% on Days 14 and 28, respectively. Corresponding efficacy for fipronil/(S)-methoprene was 48.3 and 46.4%. Lotilaner was superior to fipronil/(S)-methoprene at all post-Day 0 assessments and over the whole study period (P < 0.0001). At every post-administration evaluation, at least 81% of lotilaner-treated cats were flea-free as opposed to 25% in the fipronil/(S)-methoprene group. Lotilaner improved or eliminated clinical signs of FAD, including pruritus. Both products were well tolerated. CONCLUSIONS: Under field conditions in Europe, lotilaner flavored chewable tablets for cats displayed an efficacy against fleas higher than 97%; clinical signs of FAD were improved or eliminated. Lotilaner tablets were safe and provided superior flea control to fipronil/(S)-methoprene.

A randomized, controlled field study to assess the efficacy and safety of lotilaner (Credelio™) in controlling ticks in client-owned cats in Europe.

BACKGROUND: There is a continuing need for novel approaches to tick infestations treatment and control in cats. Lotilaner, an isoxazoline with rapid onset of action, has proven its efficacy against ticks in laboratory studies. A study was undertaken to confirm lotilaner's efficacy and safety in client-owned cats, at the minimum dose of 6.0 mg/kg, against the most common ticks infesting cats in Europe. METHODS: Twenty clinics in Germany, Hungary and Portugal participated in the study. Households with no more than three cats were randomized 2:1 to a lotilaner or fipronil group. The first household cat with at least three live, attached ticks was the primary cat. Treatments were dispensed on days 0, 28 and 56 for owner administration. Tick counts were performed on days 0, 7, 14, 21, 28, 42, 56, 70 and 84 (primary cats) and supplementary cats were assessed for safety only, on days 28, 56 and 84. Efficacy was assessed by comparing mean day 0 live attached tick counts with subsequent counts. RESULTS: Most frequently retrieved ticks were Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus, with Ixodes hexagonus also present. In the lotilaner group (n = 112) efficacy (based on geometric mean tick counts) was between 98.3-100%. For fipronil (n = 57), efficacy was between 89.6-99.6%, with live attached ticks present on some cats at all time points. Mean tick counts in lotilaner-treated cats were significantly lower than in fipronil-treated cats on days 21, 28, 42 and 56 (P < 0.05). The mean percent efficacy over all post-enrolment visits was 99.6% and 96.4% (lotilaner and fipronil group, respectively), (P < 0.0001). Lotilaner was superior to fipronil for efficacy averaged over all time points (P < 0.0001) and on individual assessment days (day 14 to 70, P < 0.0394); it was non-inferior to fipronil on the other days. Owners successfully administered all treatments, and both products were well tolerated. CONCLUSIONS: CredelioTM was effective and safe for the treatment of tick infestations in client-owned cats. Efficacy lasted one month and lotilaner was superior to fipronil on most assessment days. Cure rates ranged between 94.5-100% for lotilaner and 68.4-98.2% for fipronil.

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for cancer. Due to the mechanism of action of ICIs, inflammatory reactions against normal tissue were an anticipated side effect of these agents; these immune-related adverse events have been documented and are typically low grade and manageable. Myocarditis has emerged as an uncommon but potentially life-threatening adverse reaction in patients treated with ICIs. Assessment and characterization of ICI-associated myocarditis is challenging because of its low incidence and protean manifestations. Nevertheless, the seriousness of ICI-associated myocarditis justifies a coordinated effort to increase awareness of this syndrome, identify patients who may be at risk, and enable early diagnosis and appropriate treatment. The "Checkpoint Inhibitor Safety Working Group," a multidisciplinary committee of academic, industry, and regulatory partners, convened at a workshop hosted by Project Data Sphere, LLC, on December 15, 2017. This meeting aimed to evaluate the current information on ICI-associated myocarditis, determine methods to collect and share data on this adverse reaction, and establish task forces to close the identified knowledge gaps. In this report, we summarize the workshop findings and proposed steps to address the impact of ICI-associated myocarditis in patients with cancer.

Assessment of the speed of flea kill of lotilaner (Credelio™) throughout the month following oral administration to dogs.

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.

Laboratory evaluation of the speed of kill of lotilaner (Credelio™) against Ixodes ricinus ticks on dogs.

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.

Laboratory evaluations of the immediate and sustained effectiveness of lotilaner (Credelio™) against three common species of ticks affecting dogs in Europe.

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.

Two randomized, controlled studies to assess the efficacy and safety of lotilaner (Credelio™) in preventing Dermacentor reticulatus transmission of Babesia canis to dogs.

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.

Laboratory evaluations of the immediate and sustained efficacy of lotilaner (Credelio™) against four common species of ticks affecting dogs in North America.

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.

A randomized, controlled study to assess the efficacy and safety of lotilaner (Credelio™) in controlling ticks in client-owned dogs in Europe.

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.

A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio™) in eliminating fleas in client-owned dogs in the USA.

BACKGROUND: Preclinical studies have shown that the novel isoxazoline, lotilaner (Credelio™, Elanco) administered orally to dogs, produces rapid flea and tick knockdown and sustained speed of kill for at least a month post-treatment with a wide safety margin. A field study was undertaken to validate pre-clinical results. METHODS: Dogs were enrolled at 10 veterinary clinics across the United States. Qualifying households containing up to three dogs and one primary dog with at least 10 fleas were randomized 2:1 to receive lotilaner (Credelio™, Elanco) at the recommended minimum dose of 20 mg/kg, or afoxolaner (Nexgard®, Merial), administered per label, to give a minimum dose of 2.5 mg/kg. Treatments were dispensed on Days 0, 30 and 60 for administration by owners; all household dogs received the same treatment as the primary dog. Post-enrollment flea and tick counts were made on primary dogs on Days 30, 60 and 90, and all dogs were assessed for tablet palatability and safety. RESULTS: For efficacy assessments, data were used from 111 lotilaner-treated dogs and 50 afoxolaner-treated dogs; for safety, 197 and 86 dogs, respectively. Percent reductions from baseline in geometric mean flea counts for the lotilaner group were 99.3, 99.9 and 100% on Days 30, 60 and 90, respectively, and for afoxolaner 98.3, 99.8 and 99.8% (P < 0.001, both groups, all days). On Day 90, 100% of lotilaner-treated dogs and 93% of afoxolaner-treated dogs were flea-free. Too few ticks were present to allow assessment. There were no differences in palatability between products (P = 0.2132), with, respectively, 94% and 96% of lotilaner and afoxolaner treatments accepted when offered by hand, in an empty food bowl or with food. Both treatments were well tolerated, alleviating clinical signs of flea allergy dermatitis (FAD) in dogs affected at enrollment. CONCLUSION: A single owner-administered lotilaner treatment was greater than 99% effective in reducing mean flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in a 100% reduction in flea infestations, and a substantial reduction in signs of FAD. Lotilaner flavored tablets were readily accepted under field conditions. The absence of treatment-related adverse events confirms the safety of lotilaner in dogs.