Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis

Li, Xiao; Ren, Hong; Zhang, Qianying; Zhang, Wen; Wu, Xiaojing; Xu, Yu; Shen, Ping; Chen, Nan

doi:10.1093/ndt/gfr484

Cited by 140 publications

(93 citation statements)

References 30 publications

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“…Furthermore, 10-year renal survival rates of 81-98% have been reported in Asian LN patients, compared with 68-95% in Caucasians and 38-70% in Afro-Americans [4,12,15,16,17]. It is probable that the high response rates to immunosuppressive treatment observed in Asian LN patients contribute to the relatively favorable long-term outcomes in Asian patients [18,19,20,21]. Chronic renal insufficiency in Asian LN patients is often associated with repeated nephritic flares, each resulting in cumulative attrition of the nephron mass and renal reserve.…”

Section: Epidemiology Clinical Features and Genetics Of Ln: An Asianmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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Background: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages: Treatment responses and clinical outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. Facts from East and West: (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access...

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Section: Epidemiology Clinical Features and Genetics Of Ln: An Asianmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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“…Among them, 2 studies compared tacrolimus with placebo (Miyasaka et al 2009) or MMF (Mok et al 2010), and 3 studies (Bao et al 2007;Bao et al 2008;Bao et al 2009) compared tacrolimus plus MMF with IVCYC were excluded. At last, 5 eligibility citations (Zhang et al 2006a;Zhang et al 2006b;Xu et al 2007;Chen et al 2011;Li et al 2011), including 2 in English and 3 in Chinese, were included in the metaanalysis. We present reasons for study exclusion and progress through stages in Fig.…”

Section: Study Selectionmentioning

confidence: 99%

“…Recently, some small-scale trials (Zhang et al 2006a;Xu et al 2007;Chen et al 2011;Li et al 2011) compared tacrolimus with IVCYC in the treatment of LN; however, these studies' results were different. Therefore, we performed present meta-analysis of available RCTs to compare efficacy and safety between tacrolimus (oral administration and/or IV injection) and IVCYC in the induction treatment for LN.…”

mentioning

confidence: 99%

A Meta-Analysis of Randomized Controlled Trials Comparing Tacrolimus with Intravenous Cyclophosphamide in the Induction Treatment for Lupus Nephritis

Deng

Huo

et al. 2012

Tohoku J. Exp. Med.

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Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). As a standard treatment regimen for remission induction of proliferative LN, intravenous cyclophosphamide (IVCYC) and corticosteroids has been widely accepted. However, cyclophosphamide (CYC) is associated with significant adverse effects. Tacrolimus, a T-cell-specific calcineurin inhibitor, shares similar immunosuppressive actions with cyclosporine. We performed a meta-analysis of randomized controlled trials (RCTs) to compare efficacy and safety between tacrolimus (oral administration and/or IV injection) and IVCYC in the induction treatment for LN. We identified 5 trials, including 225 patients. Meta-analysis showed that tacrolimus could significantly increase complete remission (RR 1.61, 95% CI, 1.17 to 2.23; P = 0.004), response rate (RR 1.25, 95% CI, 1.09 to 1.44; P = 0.001), serum albumin level (SMD 1.11, 95% CI, 0.17 to 2.06; P = 0.02) and anti-dsDNA negative conversion rate (RR 1.34, 95% CI, 1.01 to 1.78; P = 0.04), and decrease urine protein (SMD −0.52, 95% CI, −0.83 to −0.22; P = 0.0008), systemic lupus erythematosus disease activity index (SLE-DAI) (SMD −0.59, 95% CI, −1.00 to −0.19; P = 0.004) compared with that of IVCYC. The rates of gastrointestinal symptoms and irregular menstruation (or amenorrhea) were significantly lower in tacrolimus group than IVCYC group (RR 0.46, 95% CI, 0.22 to 0.93; P = 0.03 and RR 0.14, 95% CI, 0.04 to 0.50; P = 0.003). In conclusion, tacrolimus was found to be more effective and safer than IVCYC as an induction therapy for Chinese LN patients.

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“…In clinical trials of LN which evaluated outcomes at 6 months, CR was 24-76% in patients treated with Cy, 7,8,[21][22][23] Moreover, in a cohort study, 52% of LN reached CR after 2 years of treatment with standard regimens. 9 Hence, some proportion of patients with LN cannot reach CR within 1 year, particularly in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Response to combination of mycophenolate mofetil, cyclosporin A and corticosteroid treatment in lupus nephritis patients with persistent proteinuria

2017

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Objective: To study the response of lupus nephritis (LN) patients with persistent proteinuria (≥ 1 g/day after ≥ 6 months corticosteroid and single immunosuppressant treatment, or ≥ 3 g/day after ≥ 3 months of corticosteroid and single immunosuppressant treatment) to corticosteroid combined with two immunosuppressants, and to evaluate associated factors of response within 1 year.Method: A retrospective study of proteinuria and renal function observed in LN patients with persistent proteinuria after adding a second immunosuppressant at 3, 6, 9 and 12 months.Result: Twenty-one LN patients (100.0% female) with persistent proteinuria were treated with corticosteroid and two immunosuppressants (mycophenolate mofetil [MMF] plus cyclosporine A [CSA]). Their mean age and duration from first immunosuppressant to initiating a combination therapy were 33.2 AE 10.2 years and 17.5 AE 15.7 months, respectively. Twelve (57.1%) patients had proteinuria levels ≥ 3 g/day. The renal pathology from 18 patients were Classes III or IV in 11 (61.1%). Fifteen patients (71.4%) responded to treatment (complete remission [CR], proteinuria ≤ 0.5 g/day, in seven patients and partial remission [PR], proteinuria reduced > 50%, in eight patients). Changing from a single immunosuppressant to combined immunosuppressants was associated with CR within 1 year (hazards ratio = 0.88; 95% CI = 0.78-0.99). Adverse events consisted of one patient with severe infection, two herpes zoster and one with transient increased serum creatinine level.Conclusion: Approximately 70% of LN patients with persistent proteinuria responded to MMF plus CSA. However, infection should be a concern with these patients.

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Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis

Cited by 140 publications

References 30 publications

Lupus Nephritis in Asia: Clinical Features and Management

Lupus Nephritis in Asia: Clinical Features and Management

A Meta-Analysis of Randomized Controlled Trials Comparing Tacrolimus with Intravenous Cyclophosphamide in the Induction Treatment for Lupus Nephritis

Response to combination of mycophenolate mofetil, cyclosporin A and corticosteroid treatment in lupus nephritis patients with persistent proteinuria

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