Issue: 2014 > November > original article

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



ORIGINAL ARTICLE
S. Arends, J.H.M. Berden, C. Grootscholten, R.H.W.M. Derksen, S.P. Berger, R.G.L. de Sévaux, A.E. Voskuyl, M. Bijl
AbstractPDF

Abstract

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.