Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Azathioprine Versus Mycophenolate Mofetil for Maintenance Immunosuppression of Proliferative Lupus Nephritis: Results of a Randomized Trial (MAINTAIN)
Houssiau1, Frederic A., D'Cruz2, David P., Sangle2, Shirish R., Remy3, Philippe, Vasconcelos4, Carlos, de Ramon Garrido5, Enrique, Gilboe Sr.6, Inge-Margrethe
Universite catholique Louvain, Brussels, Belgium,
Autoimmune Diseases. Hospital Clínic, Barcelona, Spain
Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, United Kingdom,
Hôpital Henri Mondor, Créteil, France,
Unidade de Imunologia Clínica - Hospital Santo António, Oporto, Portugal,
Hospital del SAS de Malaga, Malaga, Spain,
Rikshospitalet, Oslo, Norway,
Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium,
University of Athens, Athens, Greece,
Hopital Cochin, Paris, France,
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.
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 a 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.
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 (1565) 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).
After a median followup of 53 months, MMF was not superior to AZA to prevent renal relapses of lupus nephritis.
To cite this abstract, please use the following information:
Houssiau, Frederic A., D'Cruz, David P., Sangle, Shirish R., Remy, Philippe, Vasconcelos, Carlos, de Ramon Garrido, Enrique, et al; Azathioprine Versus Mycophenolate Mofetil for Maintenance Immunosuppression of Proliferative Lupus Nephritis: Results of a Randomized Trial (MAINTAIN) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1150