[18] ACR prefers MMF to CYC as initial treatment in African Americans and Hispanics based on data demonstrating higher efficacy of the former in these populations.[13, 18, 20] For Caucasian patients in Europe, an induction CYC regimen with reduced dose and duration (Euro-Lupus regimen; Table 2, Regimen B) has demonstrated comparable efficacy.[21,

22] The Euro-Lupus regimen is considered not of sufficient potency to control the severe active disease in high-risk subjects such as patients of African or Hispanic descent, who are therefore often treated with monthly pulse CYC for a total of six or seven doses. The comparative efficacy of this treatment regimen has not been GSK1120212 supplier formally evaluated in Asian patients. The ACR recommends that the Euro-Lupus regimen can be used in Caucasians with European background, followed by maintenance with MMF or AZA.[18] The Euro-Lupus regimen is also recommended by EULAR/ERA-EDTA as an alternative to MMF in the initial treatment of severe LN.[17] Prolonged courses (up to one year) of oral CYC were associated with more adverse effects compared find protocol with intravenous CYC.[18, 19] Oral CYC for 6 months combined with corticosteroids (Table 2,

Regimen C) has demonstrated efficacy and acceptable tolerability in Asian patients with diffuse proliferative and/or membranous LN.[23-28] In Chinese patients with proliferative LN, treatment with either intavenous or oral CYC have resulted in favorable long-term outcomes with 5- and 10-year renal surival of 88.7% and 82.8% respectively.[28] Although oral CYC appeared

to have better initial renal response rates, long-term clinical outcomes (doubling of serum creatinine, endstage renal failure and death) similar to that of intravenous CYC.[28] Bladder and ovarian toxicities and long-term risk of malignancies remain a concern with CYC treatment.[29, 30] The risk is related more to the cumulative CYC dose than the route of administration.[28] The KDIGO recommends a lifetime maximum of 36 grams of CYC.[16] Data from randomized NADPH-cytochrome-c2 reductase prospective studies show that MMF has at least comparable efficacy as CYC and is relatively well-tolerated in the treatment of severe LN.[15, 31-33] The response rate to CYC appears low in Black or Hispanic patients, while MMF is highly effective in Chinese patients (response rate >80%). In Chinese patients prednisolone combined with either MMF or oral CYC for 6 months showed comparable efficacy, and MMF treatment was associated with lower rates of severe infection, alopecia and amenorrhea.[31] Equivalent efficacy between MMF and intravenous pulse CYC, both combined with corticosteroids, as induction therapy has also been demonstrated in Malaysian patients with proliferative LN.