Retrospective evaluation of leflunomide as an adjunctive therapy in dogs with non-associative immune-mediated thrombocytopenia: 20 cases (2008-2021)

J Small Anim Pract. 2024 Apr;65(4):261-269. doi: 10.1111/jsap.13715. Epub 2024 Mar 3.

Abstract

Objective: To describe leflunomide as an adjunctive therapy in the treatment of non-associative immune-mediated thrombocytopenia.

Materials and methods: A retrospective study of dogs with a diagnosis of non-associative immune-mediated thrombocytopenia treated with leflunomide March 2008 to September 2021 was conducted. Data collected included signalment, clinical signs, physical examination findings and diagnostic testing performed. Medications administered, duration of hospital stay, time to platelet concentration >150×109/L and adverse events during leflunomide therapy were recorded. Relapses within a year of diagnosis were reported.

Results: A total of 20 client-owned dogs met inclusion criteria. Nineteen of 20 dogs (95%) achieved a platelet concentration >150×109/L with leflunomide and prednisone combination therapy and four dogs (21.1%) relapsed during treatment or shortly after treatment. Adverse effects included diarrhoea (n=5), mild lymphopenia (n=9) and mild intermittent anaemia (n=1). A single dog developed hepatotoxicity presumed to be secondary to leflunomide therapy that resolved after drug discontinuation. One dog was treated for aspiration pneumonia during treatment. Two dogs were euthanased while receiving leflunomide.

Clinical significance: Length of hospitalisation, time to platelet recovery, treatment response and relapse rate were comparable with alternative treatment protocols. Most adverse effects did not require leflunomide dose adjustment; however, two dogs died while undergoing leflunomide treatment and there is compelling evidence that one of these dogs experienced fatal infection secondary to immune-suppression. Hepatotoxicity remains a known complication of leflunomide treatment and serial biochemistry testing is recommended.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / veterinary
  • Dog Diseases* / diagnosis
  • Dogs
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Leflunomide / therapeutic use
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / veterinary
  • Retrospective Studies
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / drug therapy
  • Thrombocytopenia* / veterinary

Substances

  • Leflunomide
  • Immunosuppressive Agents