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Spotlight on Lupus

What is New NOT* Under the Sun

H. Michael Belmont, M.D.
Medical Director, Hospital for Joint Diseases
New York University Medical Center

Studies in the 1980ís established that the addition of a cytotoxic chemotherapy agent, cyclophosphamide often know by the brand name cytoxan, added to low doses of oral prednisone was superior to prednisone alone for treating aggressive forms of lupus kidney disease. Subsequently, research revealed that longer treatment with cytoxan (14 individual intravenous treatments over 2.5 years) was associated with fewer relapses of kidney inflammation than a shorter period of treatment (6 monthly treatments over a half year). A combination of an intravenous form of steroids, methylprednisolone, with cytoxan was more effective than either individually as reported in studies sponsored by the National Institutes of Health. However, treatment with cytoxan is not always effective and may be associated with undesirable side effects such as nausea, vomiting, hair loss, infection and temporary or permanent loss of fertility. Therefore, alternative medication that would provide benefits similar to cytoxan for kidney involvement but less toxic would be desirable.

Encouraging experience with just such as drug is now available. Cellcept, which is the brand name of a daily oral medication, mycophenolate mofetil, inhibits an enzyme pathway important in the cell type that produces harmful autoantibodies in patients with lupus. Studies have demonstrated when compared to cytoxan outcomes are equally favorable with both medications, at least over the first few years, for relief of kidney activity. Additionally, serious side effects with cellsept are less common compared to cytoxan.

Another recent approach to the treatment of serious kidney disease in lupus sequenced patients from an initial induction of a response with 6 monthly cytoxan treatments to maintenance therapy consisting of oral cellsept, oral azathioprine, or continuation of a long course of the intravenous cytoxan. All three groups of patients did well as regards their kidney disease (only one out of twenty patients in each of three treatment groups progressed to severe kidney failure) suggesting that the less toxic oral agents are an option for the longer-term suppression of lupus injury to the kidney.

In conclusion, several options are available to your treating physician for reducing the likelihood of kidney damage and may include prednisone alone for early, mild disease and for more severe or persistent disease cyclophosphamide, combinations of cyclophosphamide and intravenous steroids, azathioprine, or mycophenolate mofetil. The best choice for any individual is determined by a discussion with their personal physician and assessing variables such as particular histological variety of kidney involvement as ascertained on kidney biopsy if available, patientís age, gender, family planning interest and prior treatment results. Finally, newer and potentially safer and more effective treatment of lupus nephritis (kidney disease) may be available in the future, such as Riquent, previously known as LJP-394, rituximab, anti-BlyS, or anti-C5/eculizimab.

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While this overview is intended for those seeking technical understanding, a more general description of the disease can be found at "An Introduction to Lupus". Dr. Belmont has also posted a review of "Lupus Nephritis: Treatment Issues".

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