Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up

Mok, Chi Chiu; Ying, King Yee; Yim, Cheuk Wan; Siu, Yui-Pong; Tong, M.K.H.; To, Chi Hung; Ng, Woon Leung

doi:10.1136/annrheumdis-2014-206456

Cited by 184 publications

(113 citation statements)

References 45 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…A multitarget approach is appealing as the pathogenesis of SLE involves several immune pathways. CNIs plus corticosteroids alone have also been used for LN induction and found to be as effective as MMF for proliferative LN (98). At this time, CNI studies need to be viewed cautiously.…”

Section: Other Emerging Therapiesmentioning

confidence: 99%

Update on Lupus Nephritis

Almaani

Meara

Rovin

2016

CJASN

681

535

View full text Add to dashboard Cite

SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for lupus nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with lupus.

show abstract

Section: Other Emerging Therapiesmentioning

confidence: 99%

Update on Lupus Nephritis

Almaani

Meara

Rovin

2016

CJASN

681

535

View full text Add to dashboard Cite

show abstract

“…Full-texts of the remaining 10 articles were retrieved for further review. 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.…”

Section: Study Selectionmentioning

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.

View full text Add to dashboard Cite

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.

show abstract

“…Mok et al [59] reported the outcomes of patients with class III/IV/V LN given corticosteroids and TAC as induction therapy followed by low-dose corticosteroids and AZA maintenance, and the complete remission rate at 6 months was comparable to that for patients treated with corticosteroids and MMF for induction followed by AZA during maintenance (59 vs. 62%; p = 0.71). The two groups showed similar rates of major infection (9.2 vs. 5.4%; p = 0.53) and cumulative incidence of renal failure at 5 years (21 vs. 22%; p = 0.35) [59]. The numerically higher rate of renal flares in the TAC induction group did not reach statistical significance, and there was no definite conclusion on the impact of TAC on the long-term evolution of renal function.…”

Section: Emerging Treatments In Asia and Concluding Remarksmentioning

confidence: 99%

“…We have reported our data on the efficacy of TAC when used as add-on therapy, guided by therapeutic drug level monitoring, in patients with LN who showed persistent significant proteinuria despite treatment with other immunosuppressive agents, and in patients given long-term TAC therapy the renal survival rate at 3, 5 and 8 years was 93, 83 and 83%, respectively [50]. Mok et al [59] reported the outcomes of patients with class III/IV/V LN given corticosteroids and TAC as induction therapy followed by low-dose corticosteroids and AZA maintenance, and the complete remission rate at 6 months was comparable to that for patients treated with corticosteroids and MMF for induction followed by AZA during maintenance (59 vs. 62%; p = 0.71). The two groups showed similar rates of major infection (9.2 vs. 5.4%; p = 0.53) and cumulative incidence of renal failure at 5 years (21 vs. 22%; p = 0.35) [59].…”

Section: Emerging Treatments In Asia and Concluding Remarksmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

View full text Add to dashboard Cite

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...

show abstract

Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up

Abstract: Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).

Cited by 184 publications

References 45 publications

Update on Lupus Nephritis

Update on Lupus Nephritis

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

Lupus Nephritis in Asia: Clinical Features and Management

Contact Info

Product

Resources

About