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Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus.
Goodale, Elizabeth C; Varjonen, Katarina E; Outerbridge, Catherine A; Bizikova, Petra; Borjesson, Dori; Murrell, Dedee F; Bisconte, Angelina; Francesco, Michelle; Hill, Ronald J; Masjedizadeh, Mohammad; Nunn, Philip; Gourlay, Steven G; White, Stephen D.
Afiliação
  • Goodale EC; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.
  • Varjonen KE; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.
  • Outerbridge CA; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.
  • Bizikova P; Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.
  • Borjesson D; Department of Clinical Sciences, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
  • Murrell DF; Department of Dermatology, St George Hospital, University of New South Wales, Sydney, New South Wales, 2052, Australia.
  • Bisconte A; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • Francesco M; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • Hill RJ; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • Masjedizadeh M; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • Nunn P; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • Gourlay SG; Principia Biopharma Inc., 400 E Jamie Ct, South San Francisco, CA, 94080, USA.
  • White SD; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.
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.
Assuntos

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

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