Evaluation of One-Time Oral Oclacitinib Administration on Pruritic Behaviours After Intradermal Interleukin-31-Induced Pruritus Injections ("Reactive" Model) in Healthy Dogs: A Blinded, Randomised, Cross-Over Study.

Abstract

Background: Administration of interleukin (IL)-31 to healthy dogs has been used in preclinical drug testing to evaluate the antipruritic effect of novel medications through a "preventative" design approach (i.e., drugs are given before IL-31 administration).

Hypothesis/objectives: Develop and validate a "reactive" intradermal IL-31-induced pruritus model in healthy dogs by administering oral oclacitinib.

Animals: Eight adult, healthy research-bred beagles.

Materials and methods: A blinded, randomised, cross-over study. All dogs received either intradermal recombinant canine IL-31 with or without a single dose of oral oclacitinib given afterward; cross-over treatment was administered following a 4-week washout period.

Results: Oclacitinib reduced the total (p = 0.0252) and local (p = 0.0078) pruritic behaviour seconds after intradermal IL-31 injections. It also reduced the total seconds of scratching (p = 0.0078), chewing/biting (p = 0.0078) and head-shaking (p = 0.0255) behaviours. No significant reduction in licking was observed. Decreases in total pruritic seconds in this "reactive" model following oclacitinib administration were observed at 120-180 min (p = 0.0058), 180-240 min (p = 0.0075) and 240-300 min (p = 0.0241). Likewise, decreases in local pruritic behaviour seconds were observed at 60-120 min (p = 0.0498) and 240-300 min (p = 0.0343).

Conclusions and clinical relevance: The study established the first "reactive" canine intradermal IL-31 itch model in healthy dogs. One-time oral administration of oclacitinib significantly reduced the incidence of pruritic behaviours. Novel antipruritic medications can be assessed and compared using this "reactive" model in future preclinical trials.