A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years.
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.
Moroni
Gabriella
G
Division of Nephrology, IRCCS Ospedale Maggiore, Via Commenda 15, 20122 Milano, Italy. gmoroni@policlinico.mi.it
Doria
Andrea
A
Mosca
Marta
M
Alberighi
Ornella Della Casa
OD
Ferraccioli
Gianfranco
G
Todesco
Silvano
S
Manno
Carlo
C
Altieri
Paolo
P
Ferrara
Roberto
R
Greco
Simona
S
Ponticelli
Claudio
C
D000284:Administration, Oral; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007275:Injections, Intravenous; D007558:Italy; D008181:Lupus Nephritis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D003176:Complement C3; D003181:Complement C4; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D003404:Creatinine; D001379:Azathioprine; D011241:Prednisone; D008775:Methylprednisolone