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Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus
BACKGROUND: Interleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs. OBJECTIVE: To...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291138/ https://www.ncbi.nlm.nih.gov/pubmed/33830571 http://dx.doi.org/10.1111/vde.12943 |
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author | Fleck, Timothy J. Norris, Lori R. Mahabir, Sean Walters, Rodney R. Martinon, Olivier Dunham, Steven A. Gonzales, Andrea J. |
author_facet | Fleck, Timothy J. Norris, Lori R. Mahabir, Sean Walters, Rodney R. Martinon, Olivier Dunham, Steven A. Gonzales, Andrea J. |
author_sort | Fleck, Timothy J. |
collection | PubMed |
description | BACKGROUND: Interleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs. OBJECTIVE: To assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL‐31‐induced pruritus model. ANIMALS: Twenty‐four purpose‐bred beagle dogs (neutered males, spayed and intact females) 1.5–4.7 years old and weighing between 6 and14 kg. METHODS AND MATERIALS: Randomized, blinded, placebo‐controlled studies were designed to evaluate the antipruritic properties of lokivetmab. Laboratory beagle dogs were given either placebo, 0.125, 0.5 or 2.0 mg/kg lokivetmab, subcutaneously. IL‐31 then was administered to evaluate pruritus 3–5 h post‐placebo or ‐lokivetmab administration as well as one, seven, 14, 28, 42 and 56 days post‐dosing. Pruritus was evaluated over a 2 h window in animals by video monitoring and scored using a categorical scoring system. RESULTS: When animals were given 2.0 mg/kg lokivetmab, a significant reduction in pruritus was observed at 3–4, 4–5 and 3–5 h post‐treatment (P ≤ 0.0001). When animals were given either 0.125, 0.5 or 2 mg/kg lokivetmab, the duration of effect was dose‐dependent and statistically significant for 14, 28 and 42 days, respectively (P ≤ 0.0288). CONCLUSION: These data indicate that a single subcutaneous injection of 2 mg/kg lokivetmab produces a significant suppression of pruritus starting 3 h post‐treatment that can be sustained for 42 days. |
format | Online Article Text |
id | pubmed-9291138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92911382022-07-20 Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus Fleck, Timothy J. Norris, Lori R. Mahabir, Sean Walters, Rodney R. Martinon, Olivier Dunham, Steven A. Gonzales, Andrea J. Vet Dermatol Supporting Original Studies BACKGROUND: Interleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs. OBJECTIVE: To assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL‐31‐induced pruritus model. ANIMALS: Twenty‐four purpose‐bred beagle dogs (neutered males, spayed and intact females) 1.5–4.7 years old and weighing between 6 and14 kg. METHODS AND MATERIALS: Randomized, blinded, placebo‐controlled studies were designed to evaluate the antipruritic properties of lokivetmab. Laboratory beagle dogs were given either placebo, 0.125, 0.5 or 2.0 mg/kg lokivetmab, subcutaneously. IL‐31 then was administered to evaluate pruritus 3–5 h post‐placebo or ‐lokivetmab administration as well as one, seven, 14, 28, 42 and 56 days post‐dosing. Pruritus was evaluated over a 2 h window in animals by video monitoring and scored using a categorical scoring system. RESULTS: When animals were given 2.0 mg/kg lokivetmab, a significant reduction in pruritus was observed at 3–4, 4–5 and 3–5 h post‐treatment (P ≤ 0.0001). When animals were given either 0.125, 0.5 or 2 mg/kg lokivetmab, the duration of effect was dose‐dependent and statistically significant for 14, 28 and 42 days, respectively (P ≤ 0.0288). CONCLUSION: These data indicate that a single subcutaneous injection of 2 mg/kg lokivetmab produces a significant suppression of pruritus starting 3 h post‐treatment that can be sustained for 42 days. John Wiley and Sons Inc. 2021-04-08 2021-12 /pmc/articles/PMC9291138/ /pubmed/33830571 http://dx.doi.org/10.1111/vde.12943 Text en © 2021 Zoetis LLC. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Supporting Original Studies Fleck, Timothy J. Norris, Lori R. Mahabir, Sean Walters, Rodney R. Martinon, Olivier Dunham, Steven A. Gonzales, Andrea J. Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title | Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title_full | Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title_fullStr | Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title_full_unstemmed | Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title_short | Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus |
title_sort | onset and duration of action of lokivetmab in a canine model of il‐31 induced pruritus |
topic | Supporting Original Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291138/ https://www.ncbi.nlm.nih.gov/pubmed/33830571 http://dx.doi.org/10.1111/vde.12943 |
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