Leflunomide effectively treats naturally occurring immune-mediated and inflammatory diseases of dogs that are unresponsive to conventional therapy

Stanford University, Palo Alto, California, United States
Transplantation Proceedings (Impact Factor: 0.95). 01/1999; 30(8):4143-8. DOI: 10.1016/S0041-1345(98)01373-6
Source: PubMed
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    ABSTRACT: Five dogs were presumptively diagnosed with immune-mediated thrombocytopenia. As they had all been chronically treated with non-steroidal anti-inflammatory drugs, administration of immunosuppressive doses of corticosteroids was considered contraindicated. Non-steroidal anti-inflammatory drugs were temporarily discontinued in all the dogs and mycophenolate mofetil was introduced as first-line single immunomodulatory therapy. This treatment protocol resulted in complete remission of immune-mediated thrombocytopenia in all the dogs, and mycophenolate mofetil was discontinued after several months of therapy in four of the five dogs with no relapses, even when non-steroidal anti-inflammatory drug administration was resumed. The remaining dog required continued mycophenolate mofetil therapy to avoid relapse. One dog experienced diarrhoea, and another dog had diarrhoea and decreased appetite.
    Journal of Small Animal Practice 03/2014; 55(6). DOI:10.1111/jsap.12203 · 0.91 Impact Factor
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    ABSTRACT: Treatment of immune-mediated disease in dogs and cats continues to evolve as new therapies are introduced or adapted from human medicine. Glucocorticoids remain the first-line therapy for many of the immune-mediated or inflammatory diseases of cats and dogs. The focus of this article is to provide an update on some of the common immunosuppressive therapies used in small animal veterinary medicine. The goals of therapy are to induce disease remission through the inhibition of inflammation and the modulation of lymphocyte function.
    Veterinary Clinics of North America Small Animal Practice 09/2013; 43(5):1149-70. DOI:10.1016/j.cvsm.2013.04.009 · 1.04 Impact Factor
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    ABSTRACT: A high rate of mortality, expense, and complications of immunosuppressive therapy in dogs underscores the need for optimization of drug dosing. The purpose of this study was to determine, using a flow-cytometric assay, the 50% T-cell inhibitory concentration (IC50) of dexamethasone, cyclosporine, and the active metabolites of azathioprine (6-mercaptopurine) and leflunomide (A77 1726) in canine lymphocytes stimulated with concanavalin A (Con A). Whole blood was collected from 5 privately owned, healthy dogs of various ages, genders, and breeds. Peripheral blood mononuclear cells, obtained by density-gradient separation, were cultured for 72 h with Con A, a fluorochrome-tagged cell proliferation dye, and various concentrations of dexamethasone (0.1, 1, 10, 100, 1000, and 10 000 μM), cyclosporine (0.2, 2, 10, 20, 30, 40, 80, and 200 ng/mL), 6-mercaptopurine (0.5, 2.5, 50, 100, 250, and 500 μM), and A77 1726 (1, 5, 10, 25, 50, and 200 μM). After incubation, the lymphocytes were labeled with propidium iodide and an antibody against canine CD5, a pan T-cell surface marker. Flow cytometry determined the percentage of live, proliferating T-lymphocytes incubated with or without immunosuppressants. The mean (± standard error) IC50 was 3460 ± 1900 μM for dexamethasone, 15.8 ± 2.3 ng/mL for cyclosporine, 1.3 ± 0.4 μM for 6-mercaptopurine, and 55.6 ± 22.0 μM for A77 1722. Inhibition of T-cell proliferation by the 4 immunosuppressants was demonstrated in a concentration-dependent manner, with variability between the dogs. These results represent the initial steps to tailor this assay for individual immunosuppressant protocols for dogs with immune-mediated disease.
    Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire 07/2014; 78(3). · 0.85 Impact Factor