Onset and duration of action of lokivetmab in a canine model of IL-31 induced pruritus.

Abstract

BackgroundInterleukin (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.ObjectiveTo assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL‐31‐induced pruritus model.AnimalsTwenty‐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 materialsRandomized, 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.ResultsWhen 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).ConclusionThese 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.