New and future therapies for lupus nephritis
ABSTRACTBased on data from randomized controlled trials over the past decade, oral mycophenolate (CellCept) now rivals intravenous cyclophosphamide (Cytoxan) as a first-line therapy for lupus nephritis, offering similar efficacy but less toxicity. The roles of rituximab (Rituxan) and new immunomodulatory agents are being explored. Creativity in treating lupus nephritis is needed; one regimen does not fit all.
KEY POINTS
- Mycophenolate is at least equivalent to intravenous cyclophosphamide for induction and maintenance treatment of severe lupus nephritis.
- The role of rituximab is unclear, and for now it should only be used in relapsing patients or patients whose disease is resistant to standard therapy.
- Using combination therapies for induction treatment and maintenance is becoming increasingly common.
- Three-year maintenance therapy is now considered advisable in most patients.
- Entirely new drugs under study include costimulatory blockers, inhibitors of human B lymphocyte stimulator, tolerance molecules, and cytokine blockers.
INDIVIDUALIZE THERAPY
This past decade has seen such an increase in options to treat lupus nephritis that therapy can now be individualized.
Choosing IV cyclophosphamide vs mycophenolate
As a result of recent trials, doctors in the United States are increasingly using mycophenolate as the first-line drug for lupus nephritis. In Europe, however, many are choosing the shorter regimen of IV cyclophosphamide because of the results of the Euro-Lupus study.
Nowadays, I tend to use IV cyclophosphamide as the first-line drug only for patients with severe crescenteric glomerulonephritis or a very high serum creatinine level. In such cases, there is more experience with cyclophosphamide, and such severe disease does not lend itself to the luxury of trying out different therapies sequentially. If such a severely ill patient insists that a future pregnancy is very important, an alternative therapy of mycophenolate plus rituximab should be considered. I prefer mycophenolate for induction and maintenance therapy in most patients.
Dosing and formulation considerations for mycophenolate
Large dosages of mycophenolate are much better tolerated when broken up throughout the day. A patient who cannot tolerate 1 g twice daily may be able to tolerate 500 mg four times a day. The formulation can also make a difference. Some patients tolerate sustained-release mycophenolate (Myfortic) better than CellCept, and vice versa.
For patients who cannot tolerate mycophenolate, azathioprine is an acceptable alternative. In addition, for a patient who is already doing well on azathioprine, there is no need to change to mycophenolate.
Long maintenance therapy now acceptable
The ALMS Maintenance Trial12 found 3 years of maintenance therapy to be safe and effective. Such a long maintenance period is increasingly viewed as important, especially for patients in their teens and 20s, as it allows them to live a normal life, ie, to finish their education, get married, and become settled socially. Whether 5 years of maintenance therapy or even 10 years is advisable is still unknown.
Treatment during pregnancy
Neither mycophenolate nor azathioprine is recommended during pregnancy, although their effects are unknown. Because we have much more renal transplant experience with azathioprine during pregnancy, I recommend either switching from mycophenolate to azathioprine or trying to stop medication altogether if the patient has been well controlled.
