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Individualizing Therapy in Lupus Nephritis.

ABSTRACT: The ideal therapeutic approach for lupus nephritis (LN) is to quickly achieve a complete remission and maintain that response long-term while minimizing drug toxicity, and prevent tissue damage and death. The combination therapy consisting of multiple medications is aimed at incorporating drugs with complementary actions at reduced doses to achieve additive or synergistic therapeutic effects while minimizing toxicity. Here, we review the available evidence using combination therapies (triple therapy) and how such strategies can improve therapeutic efficacy in LN, which will mainly focus on the combination of high-dose corticosteroids with mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) at low dose. We discuss the rationale, efficacy, and safety of the therapy, as well as its molecular mechanisms. We also discuss the questions raised from the trials and briefly describe emerging approaches developed on the basis of combination therapy, and these advances that promise to improve on the standard-of-care treatments and toward individual therapy in LN.

SUBMITTER: An Y

PROVIDER: S-EPMC6829184 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Individualizing Therapy in Lupus Nephritis.

An Yu Y Zhang Haitao H Liu Zhihong Z

Kidney international reports 20190820 10

The ideal therapeutic approach for lupus nephritis (LN) is to quickly achieve a complete remission and maintain that response long-term while minimizing drug toxicity, and prevent tissue damage and death. The combination therapy consisting of multiple medications is aimed at incorporating drugs with complementary actions at reduced doses to achieve additive or synergistic therapeutic effects while minimizing toxicity. Here, we review the available evidence using combination therapies (triple the ...[more]

PMID: 31701046

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Project description:IntroductionLow-dose interleukin-2 (IL-2) selectively restores disturbances of regulatory T cells (Treg) and conventional T cells, resulting in the induction of remission in patients with systemic lupus erythematosus. However, to date no research has been carried out on the efficacy of low-dose IL-2 in the treatment of refractory lupus nephritis (LN). The aim of the study reported here was to investigate the renal response to low-dose IL-2 in patients with refractory LN.MethodsThe study population comprised ten patients with refractory LN who failed to achieve complete response or who had relapsed while being treated with at least two conventional immunosuppressive agents. One treatment cycle consisted of IL-2 at a dose of 1 million IU administered subcutaneously every other day for 2 weeks followed by a 2-week break. All patients received three cycles of IL-2 and were then followed up for another 12 weeks without any increase in the dose of previous immunosuppressive agents and steroids.ResultsOf the ten patients enrolled in the study, seven (70%) achieved ≥ 50% improvement in proteinuria at 12 weeks after initiating treatment with IL-2. Median proteinuria was significantly reduced by 50.3% at week 12, from 1.83 (interquartile range [IQR] 1.23-3.21) g/24 h at baseline to 0.91 (IQR 0.52-1.60) g/24 h at 12 weeks (P = 0.005). This was accompanied by a 71% reduction in urine erythrocytes, from 64/µl (IQR 24-102/µl) at baseline to 18/µl (IQR 2-20/µl) at 12 weeks (P = 0.018). Anti-dsDNA was decreased from 27.9 (IQR 7.6-40.28) IU/ml at baseline to 14.1 (IQR 7.3-20.12) IU/ml (P = 0.021) at week 12, while complements C3 and C4 were slightly increased (P = 0.445, P = 0.241, respectively). A significant expansion of Treg cells, from 9.3% at baseline to 16.6% at 12 weeks, was also found (P < 0.05). No serious adverse events occurred during the treatment period.ConclusionsLow-dose IL-2 therapy may have a promising role in the treatment of refractory LN as an alternative and safe therapeutic approach. It may be used as multi-target combination therapy in clinical practice.

Dataset Information

Individualizing Therapy in Lupus Nephritis.

Publications

Individualizing Therapy in Lupus Nephritis.

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