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SAT0201 Induction therapy with short-term high dose intravenous cyclophosphamide followed by mycophenolate mofetil in patients with proliferative lupus nephritis
  1. S. Arends1,
  2. J.H. Berden2,
  3. C. Grootscholten3,
  4. R.H. Derksen4,
  5. S.P. Berger5,
  6. R.G. de Sévaux2,
  7. A.E. Voskuyl6,
  8. M. Bijl7
  9. on behalf of the Dutch Working Party on SLE
  1. 1Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen
  2. 2Nephrology, Radboud University Nijmegen Medical Center, Nijmegen
  3. 3Internal Medicine, Kennemer Gasthuis, Haarlem
  4. 4Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht
  5. 5Internal Medicine, Erasmus MC, University Medical Center, Rotterdam
  6. 6Rheumatology, VU University Medical Center, Amsterdam
  7. 7Rheumatology, Martini Hospital Groningen, Groningen, Netherlands

Abstract

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/m2, 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/m2, 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.

  1. 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.

  2. 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

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