Immunosuppressive drugs: Beyond glucocorticoids - Veterinary Medicine
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Immunosuppressive drugs: Beyond glucocorticoids
Prednisone is likely your go-to immunosuppressant. But because of associated adverse effects, having more options would help. Azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide are commonly used for treating immune-mediated human diseases and may soon be incorporated into immunosuppressive protocols in veterinary medicine as well.



Azathioprine is a prodrug that lacks immunosuppressive effects until the liver converts it into 6-mercaptopurine (6-MP).1,2 This active metabolite highly resembles adenine and guanine, which are the purine bases that make up much of RNA and DNA. The structural similarity between these molecules results in 6-MP insertion into DNA that is being synthesized (i.e. replication) immediately preceding cell division. Random insertion of 6-MP into DNA results in nonsense mutations and eventual cell death due to disruption of a critical gene or due to apoptosis triggered by a high mutation load. The incorporation of 6-MP into DNA is also promoted by azathioprine-induced interference with purine biosynthesis, thus increasing the relative concentration of 6-MP as compared with adenine and guanine concentrations. Although 6-MP is commercially available, administration of the activated drug to people increases the prevalence of adverse affects, so is not recommended in dogs or cats.


Table 1 Published Initial Doses, Common Uses, and Suggested or Reported Concurrent Immunosuppressive Drugs for Selected Nonglucocorticoid Immunosuppressive Drugs*
Abundant anecdotal experience exists on the benefits of azathioprine for treating immune-mediated diseases in dogs, but few controlled studies have been published. Azathioprine is commonly used in dogs with immune-mediated diseases that typically require prolonged glucocorticoid treatment, including immune-mediated hemolytic anemia (IMHA), immune-mediated thrombocytopenia (ITP), systemic lupus erythematosus, immune-mediated polyarthritis, and pemphigus foliaceus (Table 1).

The primary benefit of azathioprine in these diseases is its steroid-sparing effects; simultaneous use of this drug may allow lower maintenance doses of glucocorticoids or more rapid tapering with reduced risk of disease recurrence. Azathioprine is frequently first prescribed to dogs that fail to achieve remission with glucocorticoids alone or that, after an appropriate tapering protocol, still require maintenance doses associated with severe side effects. Alternatively, because azathioprine requires at least one to two weeks to reach therapeutic serum concentrations, some veterinary internists (including myself) start azathioprine administration in patients with severe immune-mediated disease at the time of diagnosis (i.e. at the same time that glucocorticoid therapy is initiated).


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