Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus.
Vet Dermatol
; 31(4): 291-e71, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-31899567
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 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. METHODS AND MATERIALS Nine dogs diagnosed with PF were administered BTKi PRN473. Initial dosages were ≈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 the 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 At the end of the study, four responses were considered "good", two "fair", two "poor" and one dog withdrawn due to recurrence of a previously excised mast cell tumour.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 4; three sustained near complete remission by study's end. The anti-DSC-1 IgG titre decreased in three dogs, increased in two, was undetected in three and was not performed in the withdrawn dog. No dogs had detectable IgG to DSG1. Possible adverse effects occurred in three dogs. CONCLUSIONS AND CLINICAL IMPORTANCE Bruton's tyrosine kinase inhibitor monotherapy may have beneficial effects in some cases of cPF.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pênfigo
/
Inibidores de Proteínas Quinases
/
Doenças do Cão
Limite:
Animals
Idioma:
En
Revista:
Vet Dermatol
Assunto da revista:
DERMATOLOGIA
/
MEDICINA VETERINARIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos