Which JAK inhibitors are currently approved for veterinary dermatology and what are their mechanisms?

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Accepted Answer

Two JAK inhibitors are currently approved for veterinary dermatology in dogs: oclacitinib (Apoquel; Zoetis) and ilunocitinib (Zenrelia; Elanco Animal Health). Both are approved for dogs one year of age or older, and both target the JAK–signal transducer and activator of transcription (JAK–STAT) pathway to suppress pruritogenic and pro-inflammatory cytokines including IL-2, IL-4, IL-6, IL-13, and IL-31.148 Oclacitinib is a selective JAK1 inhibitor approved in the United States in 2013 for control of pruritus associated with allergic dermatitis and control of atopic dermatitis (AD) in dogs ≥12 months of age.47 In isolated enzyme assays, oclacitinib inhibited JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2) by 50% at concentrations of 10, 18, 99, and 84 nM, respectively, demonstrating 1.8-fold selectivity for JAK1 over JAK2 and 9.9-fold selectivity for JAK1 over JAK3.4 In cell-based in vitro studies, oclacitinib did not have major effects on granulocyte-macrophage colony-stimulating factor, erythropoietin, IL-12, or IL-23 at tested concentrations, reflecting its preferential activity against JAK1- and JAK3-dependent cytokines over JAK2-dependent pathways important in hematopoiesis.4 The approved dosage is 0.4–0.6 mg/kg PO twice daily for up to 14 days, then once daily thereafter.10 Up to one-third of dogs do not achieve satisfactory control of clinical signs on oclacitinib.912 Ilunocitinib is a non-selective JAK inhibitor with high potency for JAK1, JAK2, and TYK2 inhibition, approved for allergic and atopic dermatitis in dogs ≥1 year of age.18 Unlike oclacitinib, ilunocitinib is dosed at 0.6–0.8 mg/kg PO once daily throughout the treatment course, without a frequency reduction at day 14.912 The fixed once-daily schedule avoids the pruritus rebound seen with oclacitinib when dosing is stepped down from twice to once daily at day 14.9 At day 28, 83% of ilunocitinib-treated dogs achieved treatment success (defined as ≥50% reduction from baseline pruritus Visual Analog Scal