Mycophenolate Mofetil versus Azathioprine in the Maintenance Therapy of Lupus Nephritis

Abstract

Background. Renal involvement is one of the major determinants of the outcome in patients with systemic lupus erythematosus. Renal involvement contributes to both morbidity and mortality of the patients as well as indirectly through side effects of therapy directed at the renal lesions. The aim of the study was to evaluate the efficacy of mycophenolate mofetil (MMF) and azathioprine (AZA) in the maintenance therapy of lupus nephritis. Methods. Thirty-two patients from our center with diagnosed lupus nephritis World Health Organization Class III, IV, V were treated with IVC (0.75-1g/month) for six months in addition to steroid therapy, and then with AZA (n = 15) or MMF (n = 17) as a maintenance therapy. The efficacy of two drugs was compared with changes in serum creatinine, creatinine clearance, 24 hour urine protein excretion, cholesterol, anti-dsDNA antibody, and urine sediment. Results. Mean follow-up time was 41.5 + 7 months. The total remission occurred in 84% of patients (82% with MMF and 87% with AZA), with a complete remission rate of 59.3% (58% with MMF and 60% with AZA) and a partial remission rate of 25% (22% with MMF and 27% with AZA). The urinary protein excretion before MMF treatment was 1.9 + 1 g/dL and decreased significantly to 0.91 + 0.6 g/dL (p = 0.028) after treatment, and decreased from 1.58 + 0.7g/dL to 0.4 + 0.23g/dL in the AZA group (p = 0.04). The serum creatinine level decreased from 1.32 + 0.7 mg/dL to 1.12 + 0.68 mg/dL in the MMF group (p = 0.23), and decreased from 0.91 + 0.23mg/dL to 0.88 + 0.23 mg/dL in the AZA group (p = 0.49). There was no significant change between two groups (p = 0.1). The serum cholesterol decreased from 229 + 57 mg/dL to 171 + 9 mg/dL (p = 0.002), and serum triglyceride level decreased from 228 + 116 mg/dL to 98 + 35 mg/dL (p = 0.004) in the MMF treatment, but no significant change was seen in AZA group. There was no significant difference between the two groups considering the rates of doubling of serum creatinine, progression to end-stage renal failure, relapses, and documented side effects, as well. Conclusion. Both therapeutic approaches with MMF or AZA, in combination with corticosteroids, are effective as a maintenance therapy for lupus nephritis.

Mycophenolate as Maintenance Therapy for Lupus Nephritis with Impaired Renal Function

“…Most studies analyze patients with normal renal function [8,13,18,19,20], and only two included cases with elevated serum creatinine and/or decreased eGFR at the initiation of maintenance therapy with MF [9,11]. However, no studies include subanalyses of the effect of baseline renal function on renal relapse and response.…”

“…During the last decade, the results of at least 9 trials have been reported [8,9,11,12,13,14,15,16,17], and several retrospective studies [18,19,20] have focused on the best drug schedule in the maintenance phase of treatment of LN. The results allow us to conclude that short-term induction with intravenous CYC followed by maintenance therapy with MF or AZA was more efficacious than other treatment schedules [11,12,13,15].…”

Updates on the Treatment of Lupus Nephritis

“…[37][38][39] These agents are superior to continued intravenous cyclophosphamide in both preventing lupus nephritis flares and maintaining kidney function. Of equal importance, these agents show significantly lower rates of long-term toxicity, including an approximately 80% lower risk for amenorrhea and 65 to 70% lower risk for infection.…”

Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis

“…4,5 There has been mounting interest in the use of mycophenolate mofetil as induction therapy, maintenance therapy, or both for patients with lupus nephritis. [6][7][8][9][10][11][12] The Aspreva Lupus Management Study (ALMS), which examined the efficacy and safety of induction therapy with mycophenolate mofetil as compared with intravenous cyclophosphamide (plus standardized tapering of glucocorticoid therapy) in patients with active lupus nephritis (renal-biopsy active class III, IV, or V [13][14][15][16] [according to the International Society of Nephrology and Renal Pathology Society 2003 Classification of Lupus Nephritis 17 ]), showed no significant difference between the two drugs. 13 (For a description of the classes of renal biopsy used in this study, see the protocol, available with the full text of this article at NEJM.org.)…”