Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fleck, Timothy J., Norris, Lori R., Mahabir, Sean, Walters, Rodney R., Martinon, Olivier, Dunham, Steven A., Gonzales, Andrea J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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
_version_ 1784749074233163776
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
work_keys_str_mv AT flecktimothyj onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT norrislorir onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT mahabirsean onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT waltersrodneyr onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT martinonolivier onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT dunhamstevena onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus
AT gonzalesandreaj onsetanddurationofactionoflokivetmabinacaninemodelofil31inducedpruritus