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The treatment of proliferative lupus nephritis (LN) can be staged as a period of intensive immunosuppressive therapy aimed at halting immunological injury (induction therapy) followed by a period of less aggressive maintenance therapy to consolidate the response. Maintenance therapy should be continued into the period of disease quiescence to decrease the number of flares and renal damage accrual.1 Randomised controlled trials (RCTs) have shown that adjunctive immunosuppressive agents are more effective than glucocorticoids alone in protecting against the risk of progression to end-stage renal disease (ESRD). Long-term (>10 years) efficacy has been demonstrated only for cyclophosphamide (CY)-based regimens1,–,3; however, CY is associated with gonadal toxicity, which is both dose- and age-dependent.4 Mycophenolate mofetil (MMF), with little if any gonadal toxicity, has been examined as an alternative to CY for both induction and maintenance therapies. MMF has been shown in several RCTs to achieve comparable short-term rates of partial remission of LN, but it remains to be proved whether it will ultimately be as effective as CY in pre-empting ESRD.
Irrespective of the choice of induction therapy, there is broad consensus that maintenance therapy must be well tolerated, reasonably affordable and have intrinsically low rates of toxicity. Currently, the two most common choices for maintenance therapy are MMF and azathioprine (AZA). These two agents have distinct but similar mechanisms of action as purine antimetabolites. There is ongoing controversy about the objective evidence for the superiority of MMF over AZA as maintenance therapy in organ transplantation as well as in other immune-mediated diseases.5 As a result, some have argued that the lack of objective superiority of MMF on organ survival does not justify the 16-fold higher cost of MMF over AZA, although it is expected to be reduced after the patent expires at …
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