Efficacy of mizoribine-tacrolimus-based induction therapy for pediatric lupus nephritis

Tanaka, Hiroshi; Aizawa, Tomomi; Watanabe, Shojiro; Oki, Eishin; Tsuruga, Kazushi; Imaizumi, Taddatsu

doi:10.1177/0961203314528553

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…Its actions are thus similar to those of MMF. While the drug appears to be effective and well tolerated and thus is extensively used in Japan in combination with corticosteroids for induction or maintenance [60,61], or as part of triple immunosuppression together with corticosteroids and TAC for induction [62], there is relatively little published data in the English literature on this topic, and there are recent reports suggesting that the optimum dose of mizoribine in LN treatment remains to be determined [63]. …”

Section: Emerging Treatments In Asia and Concluding Remarksmentioning

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: Emerging Treatments In Asia and Concluding Remarksmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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“…followed a cohort of children with lupus nephritis treated with TAC; the results suggest that TAC is beneficial with low cytotoxicity [12,13]. A new treatment option in patients who were refractory to the standard treatment is the multitarget treatment such as a combination of TAC and MMF [20,21].…”

Section: Discussionmentioning

confidence: 99%

Combination of tacrolimus and mycophenolate mofetil in persistent proteinuria due to refractory childhood lupus nephritis

Almutairi

Alkathiri

Al‐Mayouf

2018

International Journal of Pediatrics and Adolescent Medicine

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BackgroundChildren with lupus nephritis particularly, diffuse proliferative and membranous glomerulonephritis, may necessitate potent immunosuppressive medications and occasionally combined therapy.ObjectiveTo report the beneficial effects of tacrolimus (TAC) in children with refractory lupus nephritis from a single tertiary pediatric rheumatology clinic.MethodsThis is a retrospective case series of children with refractory lupus nephritis treated with TAC after failure of aggressive immunosuppressive treatment. All patients were evaluated at the time of initiation of TAC and at last follow-up visit by assessing the following response parameters: cSLE Disease Activity Index (SLEDAI), urine protein/creatinine ratio, urine sediments, serum albumin, complement (C3 and C4), anti-double-stranded DNA (dsDNA) antibody levels, and renal function assessed by glomerular filtration rate (eGFR).ResultsThree children (two girls and one boy) with lupus nephritis and persistent nephrotic-range proteinuria failed prednisone treatment as well as sequential treatment of cyclophosphamide, mycophenolate mofetil (MMF), and rituximab. When TAC was administered along with MMF and prednisone, all patients showed improvement in response parameters, namely, SLEDAI, serum albumin, and proteinuria, and prednisone doses were significantly weaned off and discontinued in two patients. However, eGFR remained stable during the treatment period. TAC was well tolerated, and no adverse effects were observed.ConclusionTAC combined with MMF can be considered as an alternative therapeutic option for children with refractory lupus nephritis particularly those with persistent nephrotic-range proteinuria.

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“…110 Other anecdotal reports suggest that mizori bine has increased efficacy when given at high doses with Eculizumab REVIEWS corticosteroids, with or without tacrolimus, as induction immunosuppression for lupus nephritis. [111][112][113][114] Leflunomide Leflunomide prevents lymphocyte proliferation by inhibiting dihydroorotate dehydrogenase, an enzyme that catalyses de novo pyrimidine biosynthesis. Leflunomide has proven efficacy in the treatment of immunemediated arthritis but is associated with serious adverse effects, such as skin rash, diarrhoea, elevations in liver enzyme levels and thrombocytopenia.…”

Section: Mizoribinementioning

confidence: 99%

Treatment of severe lupus nephritis: the new horizon

Chan

2014

Nat Rev Nephrol

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Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

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Efficacy of mizoribine-tacrolimus-based induction therapy for pediatric lupus nephritis

Abstract: Multitarget therapy may be an attractive option for the treatment of pediatric-onset LN. Further studies involving a larger number of patients are needed.

Cited by 19 publications

References 22 publications

Lupus Nephritis in Asia: Clinical Features and Management

Lupus Nephritis in Asia: Clinical Features and Management

Combination of tacrolimus and mycophenolate mofetil in persistent proteinuria due to refractory childhood lupus nephritis

Treatment of severe lupus nephritis: the new horizon

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