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

被引：146

作者：

Fernandez-Juarez, Gema ^{[1
]}

Rojas-Rivera, Jorge ^{[2
]}

van de Logt, Anne-Els ^{[3
]}

Justino, Joana ^{[4
]}

Sevillano, Angel ^{[5
]}

Caravaca-Fontan, Fernando ^{[5
]}

Avila, Ana ^{[6
]}

Rabasco, Cristina ^{[7
]}

Cabello, Virginia ^{[8
]}

Varela, Alfonso ^{[9
]}

Diez, Montserrat ^{[10
]}

Martin-Reyes, Guillermo ^{[11
]}

Goicoechea Diezhandino, Marian ^{[12
]}

Quintana, Luis F. ^{[13
]}

Agraz, Irene ^{[14
]}

Ramon Gomez-Martino, Juan ^{[15
]}

Cao, Mercedes ^{[16
]}

Rodriguez-Moreno, Antolina ^{[17
]}

Rivas, Begona ^{[18
]}

Galeano, Cristina ^{[19
]}

Bonet, Jose ^{[20
]}

Romera, Ana ^{[21
]}

Shabaka, Amir ^{[1
]}

Plaisier, Emmanuelle ^{[22
,23
,24
]}

Espinosa, Mario ^{[7
]}

Egido, Jesus ^{[2
]}

Segarra, Alfonso ^{[14
]}

Lambeau, Gerard ^{[4
]}

Ronco, Pierre ^{[22
,23
,24
]}

Wetzels, Jack ^{[3
]}

Praga, Manuel ^{[5
,25
]}

机构：

[1] Hosp Univ Fdn Alcorcon, Div Nephrol, Madrid, Spain

[2] Hosp Univ Fdn Jimenez Diaz, Div Nephrol, Madrid, Spain

[3] Radboud Univ Nijmegen, Div Nephrol, Med Ctr, Nijmegen, Netherlands

[4] Univ Cote Azur, Ctr Natl Rech Sci CNRS, Inst Pharmacol Mol & Cellulaire IPMC, Valbonne Sophia Antipo, France

[5] Hosp Univ 12 Octubre, Div Nephrol, Inst Invest, Madrid, Spain

[6] Hosp Dr Peset, Div Nephrol, Valencia, Spain

[7] Hosp Reina Sofia, Div Nephrol, Cordoba, Spain

[8] Hosp Virgen Rocio, Div Nephrol, Seville, Spain

[9] Hosp Virgen Victoria Malaga, Div Nephrol, Malaga, Spain

[10] Autonomous Univ Barcelona UAB, Inst Invest Biosanitaria Sant Pau, Div Nephrol, Fundacio Puigvert, Barcelona, Spain

[11] Hosp Reg Univ Malaga, Div Nephrol, Malaga, Spain

[12] Hosp Gen Univ Gregorio Maranon, Div Nephrol, Madrid, Spain

[13] Univ Barcelona, Hosp Clin Barcelona, Ctr Referencia Enfermedad Glomerular Compleja Sis, Barcelona, Spain

[14] Hosp Univ Vall Hebron, Div Nephrol, Barcelona, Spain

[15] Hosp San Pedro Alcantara, Div Nephrol, Caceres, Spain

[16] Hosp Univ A Coruna, Div Nephrol, La Coruna, Spain

[17] Hosp Clin San Carlos, Div Nephrol, Madrid, Spain

[18] Hosp Univ La Paz, Div Nephrol, Madrid, Spain

[19] Hosp Univ Ramon & Cajal, Div Nephrol, Madrid, Spain

[20] Hosp Badalona Germans Trias & Pujol, Div Nephrol, Barcelona, Spain

[21] Hosp Ciudad Real, Div Nephrol, Ciudad Real, Spain

[22] Univ Pierre & Marie Curie Paris 06, Sorbonne Univ, Paris, France

[23] Inst Natl Sante & Rech Med, Unite Mixte Rech S1155, Paris, France

[24] Sorbonne Univ, Hop Tenon, Hop Jour Nephrol, Assistance Publ Hop Paris APHP,Ctr Reference Mala, Paris, France

[25] Univ Complutense Madrid, Dept Med, Madrid, Spain

来源：

KIDNEY INTERNATIONAL | 2021年 / 99卷 / 04期

关键词：

corticosteroids; cyclophosphamide; primary membranous nephropathy; rituximab; tacrolimus; NEPHROTIC SYNDROME; PHOSPHOLIPASE-A2; RECEPTOR; PLUS CYCLOPHOSPHAMIDE; RANDOMIZED-TRIAL; FOLLOW-UP; CYCLOSPORINE; STEROIDS; METHYLPREDNISOLONE; CHLORAMBUCIL; REMISSION;

D O I：

10.1016/j.kint.2020.10.014

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of antiPLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroidcyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

引用

页码：986 / 998

页数：13

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