Received December 25, 2005
Accepted on May 12, 2006

ORIGINAL ARTICLES

A Randomized Pilot Trial Comparing Cyclosporine and Azathioprine for Maintenance Therapy in Diffuse Lupus Nephritis over Four Years

Gabriella Moroni ^*1, Andrea Doria , Marta Mosca , Ornella Della Casa Alberighi , Gianfranco Ferraccioli ^||, Silvano Todesco , Carlo Manno ^¶, Paolo Altieri ^*, Roberto Ferrara , Simona Greco , and Claudio Ponticelli ^*

*Division of Nephrology, IRCCS Ospedale Maggiore, Milan, Italy; Division of Rheumatology, University of Padua, Padua, Italy; Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy; MedChild Institute, G. Gaslini Foundation, Genoa, Italy, and Serono International, Clinical Research and Development, Geneva, Switzerland; ||Division of Rheumatology, Catholic University, Rome, Italy; ¶Division of Nephrology, University of Bari, Bari, Italy; *Division of Nephrology, Ospedale Brotzu, Cagliari, Italy; Novartis Farma Origgio, Varese, Italy; and IRCCS Istituto Auxologico Italiano, Milan, Italy

¹ To whom correspondence should be addressed. E-mail: gmoroni{at}policlinico.mi.it.

	Abstract

There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.8 ± 3.57 to 0.4 ± 0.85 g/d (P < 0.0001) in the cyclosporine group and from 2.2 ± 1.94 to 0.5 ± 0.78 g/d (P < 0.0002) in the azathioprine group. After 4 yr, mean proteinuria was 0.2 ± 0.24 and 0.3 ± 0.33 g/d, respectively. At the core study end and at the follow-up completion, creatinine clearance and BP levels did not change significantly from baseline in either group. Five of 36 patients who were receiving cyclosporine and four of the 33 who were receiving azathioprine stopped the treatment because of adverse effects. For patients with diffuse proliferative lupus nephritis, azathioprine or cyclosporine combined with corticosteroids demonstrated equal efficacy in the prevention of flares.