1150 - Azathioprine Versus Mycophenolate Mofetil for Maintenance Immunosuppression of Proliferative Lupus Nephritis: Results of a Randomized Trial (MAINTAIN)

Monday, October 19, 2009: 11:30 AM
Ballroom AB (Pennsylvania Convention Center)
Frederic A. Houssiau1, David P. D'Cruz2, Shirish R. Sangle2, Philippe Remy3, Carlos Vasconcelos4, Enrique de Ramon Garrido5, Inge-Margrethe Gilboe Sr.6, Isabelle Ravelingien7, Maria Tektonidou8, Genevieve Depresseux1, Loic P. Guillevin9 and Ricard Cervera10, 1Universite catholique Louvain, Brussels, Belgium, 2Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, United Kingdom, 3Hôpital Henri Mondor, Créteil, France, 4Unidade de Imunologia Clínica - Hospital Santo António, Oporto, Portugal, 5Hospital del SAS de Malaga, Malaga, Spain, 6Rikshospitalet, Oslo, Norway, 7Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium, 8University of Athens, Athens, Greece, 9Hopital Cochin, Paris, France, 10Autoimmune Diseases. Hospital Clínic, Barcelona, Spain
Presentation Number: 1150

Purpose: To demonstrate the superiority of mycophenolate mofetil (MMF) over azathioprine (AZA) as maintenance therapy of proliferative lupus nephritis in a randomized investigator-initiated open trial.

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.

Keywords: 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 .