Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

• Published in: Annals of the rheumatic diseases Vol. 69; no. 12; pp. 2083 - 2089
• Main Authors: Houssiau, Frédéric A, D'Cruz, David, Sangle, Shirish, Remy, Philippe, Vasconcelos, Carlos, Petrovic, Radmila, Fiehn, Christoph, de Ramon Garrido, Enrique, Gilboe, Inge-Magrethe, Tektonidou, Maria, Blockmans, Daniel, Ravelingien, Isabelle, le Guern, Véronique, Depresseux, Geneviève, Guillevin, Loïc, Cervera, Ricard
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.12.2010; BMJ Publishing Group; BMJ Publishing Group LTD; BMJ Group
• Series: Extended report
• Subjects: Adult; Azathioprine - adverse effects; Azathioprine - therapeutic use; Biological and medical sciences; Biopsy; Blood pressure; Clinical and Epidemiological Research; Cyclophosphamide - therapeutic use; Diseases of the osteoarticular system; Drug dosages; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids - therapeutic use; Humans; Immunomodulators; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Kidney diseases; Kidneys; Laboratories; Lupus; Lupus Nephritis - drug therapy; Male; Medical sciences; Middle Aged; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prednisolone - therapeutic use; Pregnancy; Secondary Prevention; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Young Adult; Kidney disease; Immunopathology; Connective tissue disease; Skin disease; Urinary system disease; Rheumatology; Autoimmune disease; Lupus nephritis; Long term; Immunomodulator; Immunosuppression; Systemic disease; Immunosuppressive agent; Mycophenolate mofetil; Azathioprine; Comparative study
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2010.131995

Background Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. Methods A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. Results The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. Conclusions Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.