The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Fernández-Juárez, Gema; Justino, Joana; Varela, Alfonso; Díez, Montserrat; Diezhandino, Marian Goicoechea; Bonet, J. Vilar; Plaisier, Emmanuelle; Segarra, Alfonso; Lambeau, Gérard; Ronco, Pierre; Praga, Manuel; Sevillano, Ángel; Caravaca-Fontán, Fernando; Trujillo, Hernando; Gutiérrez, Eduardo; Juárez, G. Fernández; Shabaka, Amir; Rojas-Rivera, Jorge; Egido, Jesús; Ortíz, Alberto; Goicoechea, Marián; Verdalles, Úrsula; Segarra, Alfons; Agraz, Irene; Martín-Reyes, Guillermo; Perea, Lara; Valera, Ildefonso; Martin, M; Cabello, Virginia; Pérez-Valdivia, M.Á.; Quintana, Luís F.; Blasco, Miquel; Cao, Mercedes; Muñiz, Andrés López; Ávila, Ana; Malek, T; Espinosa, Mario; Rabasco, Cristina; Díaz, Montserrat; daSilva, Iara; Bonet, Jordi; Navarro, M; Gómez-Martino, Juan Ramón; Rivas, Begoña; Rodríguez-Moreno, Antolina; Galeano, C.; Romera, A.; Huerta, Ana; Rodriguez-Paternina, E.; Vigil, Ana; Alcázar, Roberto; Paraíso, Vicente; Barrio, V.; Wetzels, Jack F.M.; Logt, Anne-Els van de; Hofstra, Julia M.

doi:10.1016/j.kint.2020.10.014

Cited by 145 publications

(147 citation statements)

References 41 publications

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“…In higher risk patients, it is recommended that they should not be used as monotherapy but in combination with rituximab or another anti-CD20 drug. In the STARMEN trial [ 8 ], rituximab was given after six months of tacrolimus which seemed to reduce the rate of relapse. In very high-risk patients with rapid deterioration of renal function, there is insufficient evidence that rituximab used in standard doses prevents development of ESRD, and cyclophosphamide is usually preferred.…”

Section: Kdigo Recommendationsmentioning

confidence: 99%

“…A major dilemma in patients with MN is efficacy versus toxicity. In theSTARMEN trial [ 8 ], there were no differences in the number of serious adverse events among patients treated with corticosteroid-cyclophosphamide as compared to those who received tacrolimus followed by rituximab. However, cumulative doses of cyclophosphamide were lower in STARMEN than in previous studies [ 6 , 16 ].…”

Section: Perspectivesmentioning

confidence: 99%

“…To reinforce efficacy of rituximab, some investigators recommend starting with CNIs owing to their hemodynamic effects including a decrease in GFR to reduce the loss of rituximab in the urine. This approach was chosen by the STARMEN investigators who infused rituximab six months after starting tacrolimus [ 8 ]; however, the time between the two treatments exceeded the time required for a hemodynamic effect, and tacrolimus also had an immunosuppressive effect as judged by the decrease of anti-PLA2R level, albeit weaker than cyclophosphamide.…”

Section: Perspectivesmentioning

confidence: 99%

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Advances in Membranous Nephropathy

Ronco

Plaisier

Dębiec

2021

JCM

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Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leapcombining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

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Section: Kdigo Recommendationsmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

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Advances in Membranous Nephropathy

Ronco

Plaisier

Dębiec

2021

JCM

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“…The STARMEN trial was designed to settle this issue: it compares a regiment of alternating corticosteroids + CYF to sequential tacrolimus + RTX treatment. Contrary to the initial hypothesis, steroid-CYF regimen yielded better efficacy, though with significantly higher rate of all adverse effects [ 42 ]. Other B-cell targeted drugs include ofatumumab, tested by Ruggenenti and Remuzzi in 11 patients with rituximab-resistant pMN [ 43 ] and a monoclonal antibody, belimumab, that in a clinical trial significantly reduced the PLA2R antibody levels during the 12 weeks of follow up [ 44 ].…”

Section: Newer Diagnosis and Treatment Algorithmsmentioning

confidence: 95%

Membranous Nephropathy: From Research Bench to Personalized Care

Moszczuk

Kiryluk

Pączek

et al. 2021

JCM

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Membranous nephropathy is a glomerulopathy that causes nephrotic syndrome and, in at least a third of cases, lasting end-stage kidney disease (ESKD). It is also a rare case of revolutionary changes in our understanding of the disease, that translates from scientific findings to real diagnosis and treatment recommendations in less than ten years. In this review we present: (1) a short history and traditional approach to patients with membranous nephropathy, (2) current recommendations and treatment options that have emerged in recent years, (3) findings of new studies, with a particular focus on serological/immunological methods, genomic and proteomic studies, still requiring validation. With further development in this field, membranous nephropathy may become one of the first nephrological conditions that apply a truly personalized approach with the omission of invasive measures such as kidney biopsy.

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“…The role of immunologic remission (depletion of anti-PLA2R antibodies) in MN was recently demonstrated in three randomized controlled trials, GEMRITUX ( 84 ), MENTOR ( 85 ) and STARMEN ( 86 ).…”

Section: Anti-podocyte Antibodies and Response To Treatmentmentioning

confidence: 98%

Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy

Tesař

Hrušková

2021

Front. Immunol.

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The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment. The serum levels of anti-podocyte antibodies also enable the prediction of renal outcomes in terms of both remission and the risk of progression to end-stage renal disease. The positivity of anti-PLA2R antibodies before renal transplantation is associated with the risk of recurrence of MN. It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are also valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B).

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The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Abstract: The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

Cited by 145 publications

References 41 publications

Advances in Membranous Nephropathy

Advances in Membranous Nephropathy

Membranous Nephropathy: From Research Bench to Personalized Care

Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy

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