Background -Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-ofconcept study in dogs with AD.Hypothesis/Objectives -The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial.Animals -Clinicians at 15 referral clinics enrolled 211 client owned dogs with a history of chronic AD.Methods -Dogs were randomized to treatment with lokivetmab (0.125, 0.5 or 2.0 mg/kg) or placebo administered subcutaneously once on Day 0. Dog owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42, 49 and 56. Clinicians assessed Canine AD Extent and Severity Index (CADESI-03) scores on days 0, 7, 14, 28, 42 and 56.Results -Treatment with lokivetmab (2 mg/kg) resulted in a greater percentage reduction from baseline in owner assessed pruritus (days 1-49) and clinician assessed CADESI-03 scores (days 7-56) compared to placebo (P < 0.05); differences were achieved in lower dose groups but at later time points and for shorter duration for both owner assessed pruritus (0.5 mg/kg, days 2-35; 0.125 mg/kg, days 7-21) and clinician assessed CADESI-03 scores (0.5 mg/kg and 0.125 mg/kg, Day 14).Conclusions and clinical importance -Lokivetmab (0.5, 2.0 mg/kg) reduced pruritus compared to placebo for at least 1 month. Level and duration of response increased with increasing dose. Further studies are needed to better understand variability in individual responses across a broader population of dogs with AD.
Background Lokivetmab (ZTS‐00103289) is a caninized anti‐canine IL‐31 monoclonal antibody that has demonstrated efficacy in reducing pruritus associated with atopic dermatitis (AD) in dogs in field trials. Hypothesis/Objectives This study evaluated the safety of lokivetmab in a randomized, double blind, placebo‐controlled trial in client owned dogs with AD with minimal restrictions on concomitant medications and co‐morbidities. Animals Clinicians at 14 veterinary clinics enrolled client owned dogs (n = 245) with chronic AD. Methods Dogs were randomized at a 2:1 ratio to receive either lokivetmab (1.0–3.3 mg/kg) or placebo administered subcutaneously on days 0 and 28. Clinicians examined dogs, and collected blood and urine for assessment of clinical pathology and immunogenicity (days 0, 28 and 42). Results There were no immediate hypersensitivity reactions (e.g. wheals, vomiting). Discomfort at administration occurred in 5.1% of dogs and was similar in frequency and severity between lokivetmab‐ and placebo‐treated groups. Pruritus was reported as an adverse event during the study less frequently in the lokivetmab‐treated group (4.9% and 19.3%, respectively); otherwise, adverse events occurred at a similar frequency between treatment groups. There were no clinically important differences between groups in clinical pathology results. Treatment‐induced immunogenicity was found in 2.5% of lokivetmab treated dogs. A wide variety of concomitant medications were used with no clinically apparent adverse interactions. Conclusions and clinical importance Among a diverse population of 162 client owned dogs with a clinical diagnosis of AD, treatment with two monthly doses of lokivetmab was safe, based on observed adverse events and clinical pathology results over a 42 day period.
Genomic diversity among 14 isolates of Blastocystis hominis from 4 different geographic locations was examined by small-subunit rRNA (ssu rRNA) restriction-fragment-length polymorphisms (RFLP) using 5 different restriction endonucleases. On the basis of the observed RFLP patterns among the isolates, a total of 12 genotypes were identified, with 7 isolates exhibiting mixed RFLP genotypes. There was no correlation between B. hominis geographic origin and RFLP banding pattern or genotype.
Lyme disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick ( Ixodes ) transmitted spirochete, Borreliella burgdorferi . Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme disease vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme disease.
Blastocystis is a common single-celled enteric parasite found in a large variety of hosts. Recent molecular analysis supports the concept that this eukaryotic organism is a stramenopile most closely related to Proteromonas lacertae, a parasite of reptiles. In this study, the internal transcribed spacer region, partial small subunit rRNA and large subunit rRNA genes from 7 Blastocystis isolates (5 human, 1 pig and 1 sheep), and a Proteromonas lacertae isolate were amplified by PCR, cloned and sequenced. Blastocystis was found to be a typical eukaryote with both ITS1 and ITS2 regions present. Phylogenetic analysis based on the entire PCR amplicon revealed that the Blastocystis isolates did not segregate according to host or geographic origin. The highest sequence identities with the conserved Blastocystis 5.8S rDNA sequence were with the stramenopiles Fibrocapsa japonica, Chattonella marina, Cylindrotheca closterium and Hyphochytrium catenoides. The most parsimonious tree based on the 5.8S rDNA sequence from P. lacertae, 11 other stramenopiles, 2 fungi, 3 algae and 3 alveolates showed Blastocystis positioned within the stramenopiles, with P. lacertae as its closest relative. This work therefore supports the hypothesis that Blastocystis is most closely related to P. lacertae, and that it should be regarded as an unusual stramenopile.
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