Lecture Link: Update on immunosuppressive therapy
In his presentations "Immunosuppressive therapy: Better use of established drugs" and "Immunosuppressive therapy: What's new?" at the 2014 American College of Veterinary Internal Medicine Forum, Andrew Mackin, BSc, BVMS, MVS, DVSc, FANCVSc, DACVIM, discussed some old favorites as well as some new drugs used to treat patients with immune-mediated diseases. However, before you embark on an immunosuppressive regimen, Dr. Mackin warned that it is critical that you have the right diagnosis.
Typically, therapy is started with prednisone at a dose of 2 mg/kg/day given orally and then tapered to 0.5 to 1 mg/kg every other day for maintenance. The decision to add a second drug is arbitrary, Dr. Mackin noted, but should be considered if glucocorticoid therapy is ineffective, clinical signs are severe, or, in the case of patients with immune-mediated hemolytic anemia, the anemia is marked, agglutination is present, or the patient is transfusion-dependent.
Remember that immunosuppressive therapy may take one to two weeks to become effective, so don't consider therapy ineffective until then. If signs are worsening or the disease is life-threatening during that time, consider adding another immunosuppressive drug.
Cyclophosphamide is a popular next choice, but Dr. Mackin said it has been found to be weakly immunosuppressive compared with other agents. The most commonly seen side effect of this medication is refractory hemorrhagic cystitis, which may occur up to 16 weeks after administration. The typical dose is 50 mg/m2 orally, which can be given four days on and three days off, but the protocol is variable. Complete blood counts should be performed regularly when using this drug because of the risk of myelosuppression.
Chlorambucil can also be considered in conjunction with a glucocorticoid at a dose of 0.1 to 0.2 mg/kg given orally every one to two days. The tablets cannot be divided, so dosing is often done in multiples of two or at different intervals in small patients (e.g. cats can be given 2 mg every second day and then tapered to every third or fourth day). Dr. Mackin noted that the cost of chlorambucil has been going up recently, so this may need to be considered as well. As with cyclophosphamide, complete blood counts should be performed regularly when using this drug because of the risk of myelosuppression.
Another common drug that can be added to glucocorticoid therapy is azathioprine. The dose is 2 mg/kg/day given orally and then 0.5 to 1 mg/kg for maintenance. Side effects with this drug are very common in cats, so Dr. Mackin does not recommend its use in this species. Azathioprine is inexpensive, but the 50-mg tablet size may present a problem in dosing for small dogs.
Vincristine is used commonly in patients with immune-mediated thrombocytopenia because it increases megakaryocytopoiesis and thrombopoiesis. Platelet numbers often increase within three to five days, which may shorten hospitalization time. The dose is 0.2 mg/kg given intravenously once; repeated dosing does not work. Care should be taken with intravenous administration, as extravasation can cause severe tissue damage and necrosis.
Cyclosporine has been around for awhile, but new formulations are microemulsified and provide better gastrointestinal absorption. This drug is a potent immunosuppressive, and patients should be monitored closely. Since the drug is concentrated in the skin, it is still the best choice for conditions such as perianal fistulas and pemphigus foliaceus.
Dr. Mackin noted that there is no clear number to aim for when assessing efficacy with therapeutic drug concentrations and that the value in measuring these concentrations may be in preventing toxicosis. The standard dose is 5 to 10 mg/kg/day given orally divided twice daily. Practitioners can consider the concurrent use of ketoconazole to allow less use of the drug if cost is a concern. There appears to be less risk of gastrointestinal side effects if cyclosporine is kept frozen. Gingival hyperplasia and idiosyncratic liver and renal toxicoses are possible. There has been some concern that this drug may increase the risk of thromboembolism because of its effects on platelet aggregation.
Leflunomide is an immunosuppressive drug used to manage arthritis in people, so it may be considered as well for immune-mediated polyarthritis in dogs either alone or in combination with prednisone. There is still little veterinary experience with this drug, and most information is anecdotal. The dose is 2 to 4 mg/kg given orally daily. It may cause hepatotoxicosis and myelosuppression.
A generic formulation of mycophenolate has recently become available, making use of this drug less cost-prohibitive. Dr. Mackin noted that there is still limited experience with mycophenolate in veterinary medicine, but it has been used to treat dogs with myasthenia gravis. The dose is 10 to 20 mg/kg given orally once or twice a day. A lower dose given twice a day appears to be better tolerated. Use mycophenolate with caution in cats.
These "Lecture Link" summaries were contributed by Jennifer L. Garcia, DVM, DACVIM, a veterinary medicine internal medicine specialist at Sugar Land Veterinary Specialists in Sugar Land, Texas.