Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of  lupus nephritis: a metaanalysis of randomized controlled trials

Deng, Jin; Luo, Lei; Lin, Zhenguo; Xie, Huan; Xie, Hua

doi:10.3906/sag-1804-57

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…Furthermore, the adverse effects of multitarget therapy consisting of a triple immunosuppressant combination, though effective at inducing remission, should be particularly considered given that adding pharmacotherapies may negatively impact quality of life. Multitarget therapy is most effective in class IV and class V LN lesions, and it has been reported that higher proportions of patients find the adverse effects of multitarget therapy intolerable compared to CPA and GC [19]. Multidrug therapy does not increase rates of infection or malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…In two studies by Deng et al and Tunnicliffe et al, a combination of MMF, TAC, and GC ("multitarget therapy") increased complete remission rates over CPA and GC alone (RR 2.38; 95% CI: 1.07-5.30) [5,19]. Zhou et al, however, did not find differences in complete remission rates between these interventions (RR 5.13; 95% CI: 0.75-35.02), but in all three meta-analyses, the largest individual study effect size showed improved outcomes with multitarget therapy [5,11,19]. Furthermore, TAC improved complete remission rates when compared individually against other agents (RR 1.48; 95% CI: 1.23-1.77) and compositely with GC against CPA and GC (RR 2.41; 95% CI: 1.8-3.99) [10,20].…”

Section: Complete and Partial Remission Rates During Induction Therap...mentioning

confidence: 99%

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Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Smıth

Park

et al. 2022

JCM

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Background: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. Result: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. Interpretation: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.

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Section: Discussionmentioning

confidence: 99%

Section: Complete and Partial Remission Rates During Induction Therap...mentioning

confidence: 99%

Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Smıth

Park

et al. 2022

JCM

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“…In fact, combination therapy with a steroid, TAc and MMF has achieved a good therapeutic effect in clinical practice in LN. Previous studies have found that the combination of TAc and MMF is more effective and safer than conventional treatment (intravenous cyclophosphamide and steroid) (9,10,21,22). Some studies have reported that TAc combined with MMF treatment may be a beneficial option for patients with LN who exhibit an inadequate response to either cyclophosphamide or MMF treatment, or had lupus flares after achieving a complete response (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle

et al. 2020

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The inhibition of mesangial cell proliferation has become an important therapy for the prevention of glomerular proliferation-associated diseases. The combined application of immunosuppressants with multiple targets presents a novel direction in the treatment of kidney diseases. The present study was designed to explore the inhibitory effects of tacrolimus (TAc) combined with mycophenolate mofetil (MMF) on the proliferation of mesangial cells based on the cell cycle. In vitro, the levels of the proliferation index markers, Ki67 and cyclin d1, in human mesangial cells (HMcs) were determined by immunofluorescence staining and western blot analysis, respectively. In mice with lupus nephritis (LN), the proliferation of mesangial cells was determined using PAS and Masson's trichrome staining, while immunohistochemistry was used to detect Ki67 and western blot analysis was employed for the evaluation of cyclin d1 levels. The expression of platelet-derived growth factor (PdGF), a proliferation-associated protein, was estimated using immunohistochemistry and western blot analysis. In patients with LN, Ki67, cyclin d1 and PdGF expression was estimated by immunohistochemistry. The transforming growth factor-β1/Smad pathway influenced by TAC and the p38 pathway influenced by MMF were also examined by western blot analysis. The results suggested that the combination of TAc and MMF at half the concentration based on the cell cycle was more effective than monotherapy in inhibiting mesangial cell proliferation in vitro and in vivo. TAc inhibited HMc proliferation by affecting the Smad2 signaling pathway. MMF inhibited HMc proliferation by affecting the p38 signaling pathway. combined treatment with TAC and MMF significantly improved the clinical indexes of patients with LN without severe adverse effects. On the whole, the findings of the present study validate and reinforce the potential use of the combination of TAc and MMF for the treatment of mesangial proliferative diseases.

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“…Clinicians need to carefully consider the choice of immunosuppressants its dose and its drug combinations. Pathological morphology and occurrence mechanism are the most important references for drug use [ 55 ]. High doses of hormone (oral prednisone 1 mg/kg) primarily block the effects of NF- κ B and inhibit various inflammatory factors.…”

Section: Clinical Use Of Cy In Induction Remission In Lnmentioning

confidence: 99%

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis

Quan

Chen

Liang

et al. 2022

BioMed Research International

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Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.

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Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials

Cited by 13 publications

References 23 publications

Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis

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