We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Open trial of Bruton's tyrosine kinase inhibitor (PRN1008) in the treatment of canine pemphigus foliaceus.
- Authors
Goodale, Elizabeth C.; White, Stephen D.; Bizikova, Petra; Borjesson, Dori; Murrell, Dedee F.; Bisconte, Angelina; Francesco, Michelle; Hill, Ronald J.; Masjedizadeh, Mohammad; Nunn, Philip; Gourlay, Steven G.; Jordan, Tyler J.M.; Emery, Carolyn B.; Outerbridge, Catherine A.
- Abstract
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 one of the most common canine autoimmune skin diseases. Objectives – To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF. Conclusions and clinical importance – BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF. 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 one of the most common canine autoimmune skin diseases. Objectives: To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF. Animals: Four privately owned dogs. Methods and materials: Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti‐desmocollin‐1 (DSC‐1) and desmoglein‐1 (DSG‐1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC). Results: All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17–33 mg/kg. Anti‐DSC‐1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog. Conclusions and clinical importance: BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.
- Subjects
PROTEIN-tyrosine kinases; KINASE inhibitors; AUTOIMMUNE diseases; SKIN diseases; PEMPHIGUS
- Publication
Veterinary Dermatology, 2020, Vol 31, Issue 5, p410
- ISSN
0959-4493
- Publication type
Article
- DOI
10.1111/vde.12878