SAT0201 Induction therapy with short-term high dose intravenous cyclophosphamide followed by mycophenolate mofetil in patients with proliferative lupus nephritis

Background For decades, high dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded as standard therapy for proliferative lupus nephritis (LN), despite serious side effects.(1) Objectives To evaluate the effect of induction therapy with short-term high dose ivCY followed by mycophenolate mofetil (MMF) on renal function and mortality in patients with proliferative LN. Methods Between January 2003 and November 2006, 74 patients with biopsy-proven proliferative LN were included in the second Dutch LN Study. All patients were treated with ivCY (750 mg/m 2 , 6 pulses in 5 months) plus oral prednisone (OP; initially 1 mg/kg/day), followed by MMF (2000 mg/day) plus OP (10 mg/day) for 18 months, and then AZA (2 mg/kg/day) plus OP (10 mg/day) (CY/MMF group). Study endpoints included the occurrence of renal relapse, end-stage renal disease (ESRD), and mortality. Results were compared to 4-year follow-up data (median 4.0 years, range 0.1-4.5) of the first Dutch LN Study.(2) In this randomized controlled trial, patients with proliferative LN were treated with high dose ivCY (750 mg/m 2 , 13 pulses in 2 years) plus OP (initially 1 mg/kg/day) (CY group; n=50) or AZA (2 mg/kg/day) combined with intravenous methylprednisolone (3x3 pulses of 1000 mg) and OP (initially 20 mg/day) (AZA/MP group; n=37). After 2 years, all patients continued with AZA (2 mg/kg/day) plus OP (10 mg/day). Results After a median follow-up of 3.8 years (range 0.1-4.5), 4 patients (5%) of the CY/MMF group had a renal relapse, one patient (1%) reached ESRD, and 2 patients (3%) died. The occurrence of renal relapses in the CY/MMF group was comparable to the CY group (HR: 1.4, 95% CI: 0.3-7.5). Significantly less renal relapses occurred in the CY/MMF group compared to the AZA/MP group (HR: 0.2, 95% CI: 0.1-0.7). The occurrence of ESRD and mortality were comparable between treatment groups. Conclusions This open-label study shows that induction therapy with short-term (5 months) high dose ivCY followed by MMF is as effective as long-term (24 months) high dose ivCY in preventing renal relapses, ESRD, and mortality in patients with proliferative LN. References Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991;34:945-50. Grootscholten C, Ligtenberg G, Hagen EC, et al. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 2006;70:732-42. Disclosure of Interest None Declared