Abstract Number: 212

A pilot study of the efficacy of a bruton’s tyrosine kinase inhibitor in the treatment of dogs with pemphigus foliaceus

D. Murrell,, S.M. Gourlay, R.J. Hill, A. Bisconte, M. Francesco, P. Smith, D. Karr, C. Outerbridge, K. Varjonen, E.C. Goodale, D. Borjesson, V.P. Werth, P.A. Nuun, S.D. White

Meeting: 2017 Dermcoll

Session Information

Date: -

Session Title: Posters

Session Time: -

Bruton’s Tyrosine Kinase (BTK) is a key downstream element of the B-cell receptor (BCR), Fc-gamma receptor and Fc-epsilon receptor. A selective inhibition of BTK activity downregulates various B-cell activities. BTK inhibitor is effective in treating multiple autoimmune diseases. PRN473 is a novel investigational BTK inhibitor that is highly selective with high affinity and prolonged occupancy. Pemphigus foliaceus (PF) is the most common cutaneous autoimmune disease in dogs. A pilot study of PRN473 in the treatment of dogs with PF was conducted to assess its efficacy and safety. Nine dogs with PF were enrolled into the study. PRN473 was dosed initially at approximately 15 mg/kg orally and following the dose adjustment, the maximum allowable dose was 45 mg/kg daily. Skin disease activity was monitored with a modified, canine pemphigus disease activity index (cPDAI) and trough BTK occupancy was measured through blood testing. All nine dogs showed clinical improvement in the first two weeks of treatment. Four dogs continued to improve and achieved good disease control by four weeks. Two dogs required the addition of low dose corticosteroids. One dog relapsed by week four and was changed to conventional immunosuppressive therapy. One dog was removed from the trial due to poor response to PRN473 but it also failed to respond to high dose corticosteroid treatment. The study suggests PRN473 as a rapidly effective monotherapy for canine PF. PRN473 may help reduce the use of high dose corticosteroids. No safety concerns have been observed in the study.