Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis

Zheng, Zhaohui; Zhang, Haitao; Peng, Xiaomei; Zhang, Chun; Xing, Changying; Xu, Gang; Fu, Ping; Ni, Zhaohui; Chen, Jianghua; Xu, Zhonggao; Zhao, Ming‐Hui; Li, Shaomei; Huang, Xiangyang; Miao, Lining; Chen, Xiaonong; Liu, Bi‐Cheng; He, Yongcheng; Li, Jing; Liu, Lijun; Kadeerbai, Haishan; Liu, Zhangsuo; Liu, Zhihong

doi:10.1001/jamanetworkopen.2022.4492

Cited by 29 publications

(15 citation statements)

References 40 publications

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“…While the overall standardized incidence ratio of cancer is higher in SLE patients, administration of CP has been shown to increase the incidence of cancers, particularly those of the urinary tract, bone marrow, and skin, prompting the use of combination therapy to prevent these side effects [89]. A recent randomized clinical trial in Chinese SLE patients comparing cyclophosphamide and tacrolimus has shown that tacrolimus has a marginally higher rate of complete response and faster recovery of kidney function [90]. In contrast to this, another trial showed that combination therapy of cyclophosphamide with rituximab followed by belimumab not only lowered the maturation of transitional to naive B cells during B-cell reconstitution but also improved the negative selection of autoreactive B cells, thereby proving beneficial over the conventional cyclophosphamide and belimumab combination [91].…”

Section: Cyclophosphamidementioning

confidence: 99%

Recent Advances in SLE Treatment Including Biologic Therapies

Alenzi¹,

D’Cruz²

2023

Systemic Lupus Erythematosus - Pathogenesis and Management

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Systemic lupus erythematosus (SLE) is a long-term multisystem autoimmune rheumatic disease that can affect the skin, joints, kidneys, lungs, heart, and central nervous system. Clinical manifestations range from mild to severe and life-threatening diseases, which could be associated with poor outcomes, including morbidity, poor quality of life, and mortality. There is no cure for SLE, and the management is guided by organ system involvement, flare prevention, managing comorbidities, and reducing damage accumulation. Hydroxychloroquine is the most common drug that is used to control lupus disease activity. Anifrolumab is an antibody that inhibits all signaling through the type I interferon receptor and is licensed for the treatment of moderate to severe SLE. Voclosporin is a calcineurin inhibitor approved for the treatment of lupus nephritis. Belimumab as a biologic agent has been approved for the management of individuals with SLE and lupus nephritis. Despite the fact that rituximab has failed to meet its primary endpoints in clinical trials for SLE, rituximab can be used according to ACR and EULAR guidelines and is commonly used off-label for severe lupus flares. There is an unmet need for new biologic and novel therapeutic approaches in the management of SLE.

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Section: Cyclophosphamidementioning

confidence: 99%

Recent Advances in SLE Treatment Including Biologic Therapies

Alenzi¹,

D’Cruz²

2023

Systemic Lupus Erythematosus - Pathogenesis and Management

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“…Another randomized, open-label, parallel control, and noninferiority study found tacrolimus was noninferior to IV CY for LN response at week 24. There was a complete or partial response rate of 83.0% (117 of 141 patients) in the tacrolimus group and 75.0% (93 of 124 patients) in the IV CY group [ 56 ]. Results of representative studies of cyclophosphamide treatment compared to MMF or calcineurin inhibitors in patients with lupus nephritis were summarized in Table 2 .…”

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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“… 137 Recently, a phase 3 study with 314 LN patients supports oral tacrolimus to be non-inferior to cyclophosphamide in induction therapy for LN, showing a more favorable safety profile than cyclophosphamide. 138 In LN patients who failed to achieve complete response after standard induction therapy, thus having a refractory condition, might profit from multitarget therapy, especially if proteinuria persists. This treatment can help patients achieve a renal response and reduce the use of steroids.…”

Section: Targeting Lupus To Control Lupus Nephritismentioning

confidence: 99%

Lupus Nephritis: Current Perspectives and Moving Forward

Lichtnekert¹,

Anders²,

Lech³

2022

JIR

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Lupus nephritis is a severe organ manifestation of systemic lupus erythematosus, and its pathogenesis involves complex etiology and mechanisms. Despite significant knowledge gains and extensive efforts put into understanding the development and relapsing disease activity, lupus nephritis remains a substantial cause of morbidity and mortality in lupus patients. Current therapies retain a significant unmet medical need regarding rates of complete response, preventing relapse of lupus nephritis, progression of chronic kidney disease to kidney failure, drug toxicity, and pill burden-related drug non-adherence. Connected to progression of chronic kidney disease are the associated risks for disabling or even lethal cardiovascular events, as well as chronic kidney disease-related secondary immunodeficiency and serious infections. In this regard, biomarkers are needed that can predict treatment response to specific drugs to enable personalized precision medicine. A series of clinical trials with innovative immunomodulatory drugs are ongoing and raise expectations for improvements in the management of lupus nephritis. Here, we review how new developments in pathogenesis connect with current and future perspectives for the management of lupus nephritis.

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Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis

Cited by 29 publications

References 40 publications

Recent Advances in SLE Treatment Including Biologic Therapies

Recent Advances in SLE Treatment Including Biologic Therapies

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis

Lupus Nephritis: Current Perspectives and Moving Forward

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