Method: 105 (mainly Caucasians) lupus patients from 29 European centers, with WHO Class III, IV, Vc or Vd nephritis and with a 24-hour proteinuria ≥ 0.5 gram were included. The number of patients was calculated to obtain a power of 0.80 with an α level of 0.05, on the basis of an anticipated 35% renal flare rate in the AZA group and a 10% flare rate in the MMF group, this difference being considered as clinically meaningful. All patients received 3 daily intravenous (IV) pulses of 750 mg methylprednisolone, followed by oral glucocorticoids (0.5 mg/kg/d equivalent prednisolone; per protocol tapering), and 6 fortnightly cyclophosphamide IV pulses of 500 mg (Euro-Lupus regimen). Based on randomization performed at baseline, AZA (target dose: 2 mg/kg/d) or MMF (target dose: 2 g/d) was started at week 12 for a total period of 60 months. Time to renal flare was the primary endpoint. Survival curves were derived using the Kaplan-Meier method and statistically tested with the Log rank test. All patients had a theoretical followup of ≥ 3 years. Analyses were by intention-to-treat.
Results: 52 and 53 patients were randomized in the AZA and MMF groups, respectively. Their baseline clinical, biological and pathological characteristics did not differ. After a median (range) followup of 53 (15-65) months, 24 patients had been dropped (mainly for pregnancy wish [n = 10; 2 AZA and 8 MMF, p = 0.05] and toxicity [n = 7; 5 AZA and 2 MMF], NS). A renal flare was observed in 13 AZA patients and 9 MMF patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Doubling of serum creatinine occured in 4 AZA and 3 MMF patients. Infectious side-effects did not differ between the groups but drug-related hematological cytopenias were statistically more frequent in the AZA group (p = 0.03).
Conclusion: After a median followup of 53 months, MMF was not superior to AZA to prevent renal relapses of lupus nephritis.
Disclosure: F. A. Houssiau, Aspreva, 5 ; D. P. D'Cruz, Aspreva, 5 ; S. R. Sangle, None; P. Remy, None; C. Vasconcelos, Aspreva, 5 ; E. de Ramon Garrido, None; I. M. Gilboe Sr., None; I. Ravelingien, None; M. Tektonidou, None; G. Depresseux, None; L. P. Guillevin, Aspreva, 5 ; R. Cervera, Aspreva, 5 .