Immunomodulatory effect of long-term oclacitinib maleate therapy in dogs with atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a chronic disease characterised by hypersensitivity to environmental allergens. Oclacitinib maleate selectively inhibits pro-inflammatory mediators associated with cAD. However, the impact of chronic oclacitinib use on immunocompetence requires further investigation. OBJECTIVES: Herein, we examined the potential immunomodulatory effects of prolonged oclacitinib treatment in dogs. ANIMALS: Thirteen privately owned dogs with cAD, treated with 0.4-0.6 mg/kg oclacitinib for 12 months. METHODS AND MATERIALS: Pruritus level was evaluated using a pruritus Visual Analog Scale (pVAS) and the canine atopic dermatitis extent and severity index, 4th iteration (CADESI IV). Peripheral blood samples were collected for routine laboratory assays and lymphocyte subtypes were analysed using flow cytometry. Antigen-specific intracellular cytokine production from CD4+ and CD8+ T lymphocytes was analysed following in vitro stimulation by Dermatophagoides farinae antigens. RESULTS: Oclacitinib treatment significantly reduced pVAS and CADESI-04 scores, by 51% and 86.7%, respectively. Flow cytometric analysis revealed increased CD4+ and CD14+ lymphocyte populations. The cytokine profile at 360 days after treatment initiation was similar to that before treatment and was not associated with clinical relapse. CONCLUSION: Oclacitinib, when administered at the currently labelled dose for one year, is associated with a significant increase in circulating CD4+ T cells, but does not alter cytokine production from antigen-stimulated T cells. The results reported do not support evidence for immunosuppression mediated by the mechanisms evaluated in this study.

Clinical-pathological and immunological biomarkers in dogs with atopic dermatitis.

Canine atopic dermatitis (CAD) is a chronic, pruritic, genetic, and inflammatory disease. Its pathogenesis is very complex and involves skin barrier defects and immune system dysfunction. This study aimed to investigate hematological, biochemical, clinical, and immunological parameters to contribute to the identification of biomarkers applied to CAD. The results of the analysis on hematologic and clinical parameters showed increased neutrophil numbers and decreased lymphocyte counts. The ex vivo immunophenotyping of leukocytes demonstrated increased counts of circulating neutrophils, in addition to a high frequency of CD4+ T-cells and elevated CD4+/CD8+ T-cell ratio, which were the hallmark of atopic animals. Moreover, atopic dogs presented a mixed immune response, displaying both CD4+ and CD8+ T-cell subsets as relevant sources of IFN-γ and IL-4 cytokines. The morbidity analyzed by the CADESI index demonstrated that CAD severity is related to the low frequency of circulating CD14+ monocytes, CD21+ B-cells, and CD8+ T-cells. The reported biomarkers would be useful in CAD monitoring for treatment and prognosis analysis.