Issue: 2014 > November > original article

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

S. Arends, J.H.M. Berden, C. Grootscholten, R.H.W.M. Derksen, S.P. Berger, , A.E. Voskuyl, M. Bijl


Background: For decades, high-dose intravenous
cyclophosphamide (ivCY) given for 24-30 months was
regarded as the standard therapy for proliferative lupus
nephritis, despite serious side effects. Our aim was to
evaluate the effect of induction therapy with short-term
high-dose ivCY followed by mycophenolate mofetil (MMF)
on disease parameters, mortality and health-related
quality of life (HRQoL) in patients with proliferative lupus
nephritis. Methods: Between January 2003 and November 2006, 71 patients with biopsy-proven proliferative lupus nephritis were included in the second Dutch Lupus Nephritis Study. All patients were treated with ivCY (750 mg/m2, six monthly pulses) plus oral prednisone, followed by MMF (2000 mg/day) plus oral prednisone for 18 months, and then azathioprine (2 mg/kg/day) plus oral prednisone. Study endpoints included the occurrence of renal relapse, end-stage renal disease (ESRD) and mortality. Results: After a median follow-up of 3.8 years (range 0.1-4.5), four (5.6%) of the 71 patients had a renal relapse, one (1.4%) failed treatment, one (1.4%) reached ESRD,
and two (2.8%) died. Systemic lupus erythematosus (SLE) Disease Activity Index, serum creatinine, proteinuria and antibodies against anti-dsDNA decreased significantly during treatment and serum levels of complement factor 3 and 4 increased significantly. Furthermore, six of eight domains of the Short Form-36 as well as the number of symptoms and total distress level according to the SLE Symptom Checklist improved significantly over time. Conclusions: This open-label study shows that induction therapy with short-term (six monthly pulses) high-dose ivCY followed by MMF is effective in preventing renal relapses, ESRD and mortality and improving HRQoL in patients with proliferative lupus nephritis.