Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus.

BACKGROUND Bruton's tyrosine kinase (BTK) is important in B cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is the most common canine autoimmune skin disease. OBJECTIVES To determine the safety and efficacy of a BTKi in cPF treatment. ANIMALS Nine privately owned dogs. MATERIALS AND METHODS Nine dogs diagnosed with PF were administered BTKi PRN473. Initial dosages approximated 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for a maximum of 20 weeks, attempting decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels, urinalyses and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin G (IgG) titres were performed before and after treatment period. Drug bound to target was measured in peripheral blood mononuclear cells. RESULTS All nine dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. At the end of the study, four responses were considered "good", two "fair", two "poor" and one dog withdrawn due to recurrence of a previously excised mast cell tumour. Four dogs continued to improve by week four; three sustained near complete remission by study's end. Anti-DSC-1 IgG titre decreased in three dogs, increased in two, was undetected in three and not performed in withdrawn dog. No dogs had detectable IgG to DSG1. Possible adverse effects occurred in three dogs. CONCLUSIONS AND CLINICAL IMPORTANCE BTKi monotherapy may have beneficial effects in some cases of cPF.

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