Leflunomide analog, MNA-715, plus cyclosporine reduces renal
allograft rejection in mismatched dogs.
Kyles AE, Gregory CR, Griffey SM, Bernsteen L, Jackson J, Morris RE
Comparative Transplantation Laboratory (A.E.K., C.R.G., L.B., J.J.), Department of
Surgical and Radiological Sciences, School of Veterinary Medicine, University of
California, Davis, Davis, California, USA
Combination of antilymphocyte globulin and leflunomide leads to
superior grafts.
Woo J, Zhang W, Gao L, Shen J, Chong A, Buelow R
SangStat, The Transplant Company, 94555, Fremont, California, USA
Immunomodulators
Leflunomide (Arava--Hoechst Marion Roussel) is a promising immunomodulating agent which is
being tested in the prevention of transplant rejection as well as in RA. It is a novel isoxazol derivative,
with disease-modifying properties. Following oral administration, the drug is rapidly metabolized to
its active form, a compound with a long elimination half-life (approximately 11 days). This metabolite
is believed to interfere with T-cell proliferation, leading to an inhibition of the synthesis of pyrimidines.
This reduces the number of proinflammatory cytokines, and leads to an anti-inflammatory effect.
Imuran is used in humans as an anti rejection drug after organ transplants but
has been used successfully in the treatment of AIHA in dogs because it like prednisone suppresses
the immune system. Because it takes Imuran several weeks to start working it is used as an
adjunctive therapy with the prednisone. Two side effects that should be noted with Imuran are bone
marrow suppression and increased susceptibly to infections. Other drugs used in the treatment of
AIHA are Cytoxan (cyclophosphamide) and Neoral (cyclosproine). Two anabolic steroid's, danazol
and winstrol are also some times used in the treatment of AIHA. Recent clinical studies at the
University of California, Davis have shown that a drug called Arava (leflumonide) also appears to be
successful in treating AIHA.