Sequential Therapies for Proliferative Lupus Nephritis

Contreras, Gabriel; Pardo, Victoriano; Leclercq, Baudouin; Lenz, Oliver; Tozman, Elaine; O'Nan, Patricia; Roth, David A.

doi:10.1056/nejmoa031855

Cited by 743 publications

(515 citation statements)

References 17 publications

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“…A recent trial by Contreras et al [22] sheds light on the relative efficacy of maintenance regimens using either MMF, AZA, or continued i.v. CYC in severe LN.…”

Section: Resultsmentioning

confidence: 99%

Mycophenolate Mofetil versus Azathioprine in the Maintenance Therapy of Lupus Nephritis

Şahin

Kızıltaş

et al. 2008

Renal Failure

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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.

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“…A recent trial by Contreras et al [22] sheds light on the relative efficacy of maintenance regimens using either MMF, AZA, or continued i.v. CYC in severe LN.…”

Section: Resultsmentioning

confidence: 99%

Mycophenolate Mofetil versus Azathioprine in the Maintenance Therapy of Lupus Nephritis

Şahin

Kızıltaş

et al. 2008

Renal Failure

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“…The efficacy and tolerability of mycophenolate mofetil combined with prednisolone have been demonstrated in Chinese patients with class IV lupus nephritis, who showed a Ͼ90% response rate and a 6.3% incidence of serum creatinine doubling over a median followup of 63 months (13). Data from studies in the US, which included high-risk subjects such as African American and Hispanic patients, showed a higher response rate (though still suboptimal, at 52%) and a lower relapse rate with mycophenolate mofetil and prednisone, compared with CYC-based induction or maintenance treatment, respectively (6,14). A cohort study in the UK has demonstrated a favorable response rate and tolerability profile with mycophenolate mofetil and prednisone as the primary treatment in Caucasian patients (4).…”

mentioning

confidence: 99%

Histologic deterioration and more flares: The case against azathioprine plus methylprednisolone in the treatment of proliferative lupus nephritis

Chan¹

2007

Arthritis & Rheumatism

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An ideal immunosuppressive treatment for severe lupus nephritis should be devoid of adverse effects but potent enough to abate the inflammatory process rapidly. Corticosteroid combined with cyclophosphamide (CYC) has been the conventional treatment, although the side effects of CYC are well recognized. In this issue of Arthritis & Rheumatism, Grootscholten et al (1) report that an immunosuppressive regimen comprising methylprednisolone (MP) (9 intravenous 1-gm pulses in 2 months)/prednisone (20 mg/day tapered to 10 mg/day over 5 months) and azathioprine (AZA) (2 mg/kg/day) given for 2 years was associated with more progression of chronic renal histopathologic lesions compared with prednisone (1 mg/ kg/day for 4 weeks tapered to 10 mg/day after 6 months) and CYC (6 intravenous 750-mg/m 2 pulses given at 4-week intervals followed by 7 pulses given at 12-week intervals) (2). These conclusions were based on findings in 39 pairs of renal biopsy samples, obtained at baseline and after 2 years of treatment. In another report from the same study it was noted that, while high response rates (ϳ90%) were achieved with both treatment regimens, relapses were more frequent in the AZA plus MP group (2).In the pathologic study (1), 10.3% of patients showed doubling of the baseline serum creatinine level at the last followup (median followup 77 months), and the AZA plus MP regimen was associated with a 5.2-fold increase in risk of this outcome compared with the CYC regimen. Thus, there was concordance between renal function and histologic end points.

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“…CYC appears to have an unacceptable safety profi le for long-term use in maintenance therapy given the risks of impaired fertility, alopecia, and hemorrhagic cystitis. 25,26 A study by Contreras et al randomized 59 patients to maintenance therapy with either quarterly CYC infusions, oral AZA, or oral MMF continued from 1 to 3 years. 26 AZA and MMF had higher event-free survival than CYC for the composite endpoint of death and chronic renal failure, and also lower risk of relapse.…”

Section: Maintenancementioning

confidence: 99%

“…25,26 A study by Contreras et al randomized 59 patients to maintenance therapy with either quarterly CYC infusions, oral AZA, or oral MMF continued from 1 to 3 years. 26 AZA and MMF had higher event-free survival than CYC for the composite endpoint of death and chronic renal failure, and also lower risk of relapse. The safety profi le was also superior for the AZA and MMF arms compared with CYC, with lower rates of hospitalization, amenorrhea, and infection.AZA and MMF have been found to have similar effi cacy in several randomized trials.…”

Section: Maintenancementioning

confidence: 99%

“…The safety profi le was also superior for the AZA and MMF arms compared with CYC, with lower rates of hospitalization, amenorrhea, and infection.AZA and MMF have been found to have similar effi cacy in several randomized trials. 26,27 Recently, the results of two important trials comparing these two agents have been publicized in abstract form. The trial of Azathioprine Versus Mycophenolate Mofetil for Maintenance Immunosuppression of Proliferative Lupus Nephritis (MAINTAIN) randomized 105 patients to either AZA or MMF for at least 3 years of maintenance (mean, 53 months).…”

Section: Maintenancementioning

confidence: 99%

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New and emerging treatments for lupus nephritis

Canetta

Appel

2011

Dialysis & Transplantation

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Sequential Therapies for Proliferative Lupus Nephritis

Abstract: For patients with proliferative lupus nephritis, short-term therapy with intravenous cyclophosphamide followed by maintenance therapy with mycophenolate mofetil or azathioprine appears to be more efficacious and safer than long-term therapy with intravenous cyclophosphamide.

Cited by 743 publications

References 17 publications

Mycophenolate Mofetil versus Azathioprine in the Maintenance Therapy of Lupus Nephritis

Mycophenolate Mofetil versus Azathioprine in the Maintenance Therapy of Lupus Nephritis

Histologic deterioration and more flares: The case against azathioprine plus methylprednisolone in the treatment of proliferative lupus nephritis

New and emerging treatments for lupus nephritis

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