Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

Gerald B. Appel; Gabriel Contreras; Mary Anne Dooley; Ellen M. Ginzler; David Isenberg; David Jayne; Lei Shi Li; Eduardo Mysler; Jorge Sánchez-Guerrero; Neil Solomons; David Wofsy; Carlos Abud; Sharon Adler; Graciela Alarcón; Elisa Albuquerque; Fernando Almeida; Alejandro Alvarellos; Gerald Appel; Hilario Avila; Cornelia Blume; Ioannis Boletis; Alain Bonnardeaux; Alan Braun; Jill Buyon; Ricard Cervera; Nan Chen; Shunle Chen; António Gomes Da Costa; Razeen Davids; David D'Cruz; Enrique De Ramón; Atul Deodhar; Andrea Doria; Bertrand Dussol; Paul Emery; Justus Fiechtner; Jürgen Floege; Hilda Fragoso-Loyo; Richard Furie; Rozina Ghazalli; Cybele Ghossein; Gary Gilkeson; Ellen Ginzler; Caroline Gordon; Jennifer Grossman; Jieruo Gu; Loïc Guillevin; Pierre Yves Hatron; Gisela Herrera; Falk Hiepe; Frederic Houssiau; Osvaldo Hübscher; Claudia Hura; Joshua Kaplan; Gianna Kirsztajn; Emese Kiss; Ghazali Ahmad Kutty; Maurice Laville; Maria Lazaro; Oliver Lenz; Leishi Li; Liz Lightstone; Sam Lim; Michel Malaise; Susan Manzi; Juan Marcos; Olivier Meyer; Pablo Monge; Saraladev Naicker; Nathaniel Neal; Michael Neuwelt; Kathy Nicholls; Nancy Olsen; Jose Ordi-Ros; Barbara Ostrov; Manuel Pestana; Michelle Petri; Gyula Pokorny; Jacques Pourrat; Jiaqi Qian; Jai Radhakrishnan; Brad Rovin; Julio Sanchez Roman; Joseph Shanahan; William Shergy; Fotini Skopouli; Alberto Spindler; Christopher Striebich; Robert Sundel; Charles Swanepoel; Yen Tan Si; Guillermo Tate; Vladimír Tesaŕ; Mohamed Tikly; Haiyan Wang; Rosnawati Yahya; Xueqing Yu; Fengchun Zhang; Diana Zoruba

doi:10.1681/ASN.2008101028

Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

Gerald B. Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M. Ginzler, David Isenberg, David Jayne, Lei Shi Li, Eduardo Mysler, Jorge Sánchez-Guerrero, Neil Solomons, David Wofsy, Carlos Abud, Sharon Adler, Graciela Alarcón, Elisa Albuquerque, Fernando Almeida, Alejandro Alvarellos, Gerald Appel, Hilario Avila, Cornelia BlumeIoannis Boletis, Alain Bonnardeaux, Alan Braun, Jill Buyon, Ricard Cervera, Nan Chen, Shunle Chen, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Atul Deodhar, Andrea Doria, Bertrand Dussol, Paul Emery, Justus Fiechtner, Jürgen Floege, Hilda Fragoso-Loyo, Richard Furie, Rozina Ghazalli, Cybele Ghossein, Gary Gilkeson, Ellen Ginzler, Caroline Gordon, Jennifer Grossman, Jieruo Gu, Loïc Guillevin, Pierre Yves Hatron, Gisela Herrera, Falk Hiepe, Frederic Houssiau, Osvaldo Hübscher, Claudia Hura, Joshua Kaplan, Gianna Kirsztajn, Emese Kiss, Ghazali Ahmad Kutty, Maurice Laville, Maria Lazaro, Oliver Lenz, Leishi Li, Liz Lightstone, Sam Lim, Michel Malaise, Susan Manzi, Juan Marcos, Olivier Meyer, Pablo Monge, Saraladev Naicker, Nathaniel Neal, Michael Neuwelt, Kathy Nicholls, Nancy Olsen, Jose Ordi-Ros, Barbara Ostrov, Manuel Pestana, Michelle Petri, Gyula Pokorny, Jacques Pourrat, Jiaqi Qian, Jai Radhakrishnan, Brad Rovin, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Yen Tan Si, Guillermo Tate, Vladimír Tesaŕ, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba

Arthritis and Rheumatic Diseases

Research output: Contribution to journal › Article › peer-review

869 Scopus citations

Abstract

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m² in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Original language	English (US)
Pages (from-to)	1103-1112
Number of pages	10
Journal	Journal of the American Society of Nephrology
Volume	20
Issue number	5
DOIs	https://doi.org/10.1681/ASN.2008101028
State	Published - May 2009

ASJC Scopus subject areas

General Medicine

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Appel, G. B., Contreras, G., Dooley, M. A., Ginzler, E. M., Isenberg, D., Jayne, D., Li, L. S., Mysler, E., Sánchez-Guerrero, J., Solomons, N., Wofsy, D., Abud, C., Adler, S., Alarcón, G., Albuquerque, E., Almeida, F., Alvarellos, A., Appel, G., Avila, H., ... Zoruba, D. (2009). Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. Journal of the American Society of Nephrology, 20(5), 1103-1112. https://doi.org/10.1681/ASN.2008101028

Appel, GB, Contreras, G, Dooley, MA, Ginzler, EM, Isenberg, D, Jayne, D, Li, LS, Mysler, E, Sánchez-Guerrero, J, Solomons, N, Wofsy, D, Abud, C, Adler, S, Alarcón, G, Albuquerque, E, Almeida, F, Alvarellos, A, Appel, G, Avila, H, Blume, C, Boletis, I, Bonnardeaux, A, Braun, A, Buyon, J, Cervera, R, Chen, N, Chen, S, Da Costa, AG, Davids, R, D'Cruz, D, De Ramón, E, Deodhar, A, Doria, A, Dussol, B, Emery, P, Fiechtner, J, Floege, J, Fragoso-Loyo, H, Furie, R, Ghazalli, R, Ghossein, C, Gilkeson, G, Ginzler, E, Gordon, C, Grossman, J, Gu, J, Guillevin, L, Hatron, PY, Herrera, G, Hiepe, F, Houssiau, F, Hübscher, O, Hura, C, Kaplan, J, Kirsztajn, G, Kiss, E, Kutty, GA, Laville, M, Lazaro, M, Lenz, O, Li, L, Lightstone, L, Lim, S, Malaise, M, Manzi, S, Marcos, J, Meyer, O, Monge, P, Naicker, S, Neal, N, Neuwelt, M, Nicholls, K, Olsen, N, Ordi-Ros, J, Ostrov, B, Pestana, M, Petri, M, Pokorny, G, Pourrat, J, Qian, J, Radhakrishnan, J, Rovin, B, Roman, JS, Shanahan, J, Shergy, W, Skopouli, F, Spindler, A, Striebich, C, Sundel, R, Swanepoel, C, Si, YT, Tate, G, Tesaŕ, V, Tikly, M, Wang, H, Yahya, R, Yu, X, Zhang, F & Zoruba, D 2009, 'Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis', Journal of the American Society of Nephrology, vol. 20, no. 5, pp. 1103-1112. https://doi.org/10.1681/ASN.2008101028

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title = "Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis",

abstract = "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.",

author = "Appel, {Gerald B.} and Gabriel Contreras and Dooley, {Mary Anne} and Ginzler, {Ellen M.} and David Isenberg and David Jayne and Li, {Lei Shi} and Eduardo Mysler and Jorge S{\'a}nchez-Guerrero and Neil Solomons and David Wofsy and Carlos Abud and Sharon Adler and Graciela Alarc{\'o}n and Elisa Albuquerque and Fernando Almeida and Alejandro Alvarellos and Gerald Appel and Hilario Avila and Cornelia Blume and Ioannis Boletis and Alain Bonnardeaux and Alan Braun and Jill Buyon and Ricard Cervera and Nan Chen and Shunle Chen and {Da Costa}, {Ant{\'o}nio Gomes} and Razeen Davids and David D'Cruz and {De Ram{\'o}n}, Enrique and Atul Deodhar and Andrea Doria and Bertrand Dussol and Paul Emery and Justus Fiechtner and J{\"u}rgen Floege and Hilda Fragoso-Loyo and Richard Furie and Rozina Ghazalli and Cybele Ghossein and Gary Gilkeson and Ellen Ginzler and Caroline Gordon and Jennifer Grossman and Jieruo Gu and Lo{\"i}c Guillevin and Hatron, {Pierre Yves} and Gisela Herrera and Falk Hiepe and Frederic Houssiau and Osvaldo H{\"u}bscher and Claudia Hura and Joshua Kaplan and Gianna Kirsztajn and Emese Kiss and Kutty, {Ghazali Ahmad} and Maurice Laville and Maria Lazaro and Oliver Lenz and Leishi Li and Liz Lightstone and Sam Lim and Michel Malaise and Susan Manzi and Juan Marcos and Olivier Meyer and Pablo Monge and Saraladev Naicker and Nathaniel Neal and Michael Neuwelt and Kathy Nicholls and Nancy Olsen and Jose Ordi-Ros and Barbara Ostrov and Manuel Pestana and Michelle Petri and Gyula Pokorny and Jacques Pourrat and Jiaqi Qian and Jai Radhakrishnan and Brad Rovin and Roman, {Julio Sanchez} and Joseph Shanahan and William Shergy and Fotini Skopouli and Alberto Spindler and Christopher Striebich and Robert Sundel and Charles Swanepoel and Si, {Yen Tan} and Guillermo Tate and Vladim{\'i}r Tesa{\'r} and Mohamed Tikly and Haiyan Wang and Rosnawati Yahya and Xueqing Yu and Fengchun Zhang and Diana Zoruba",

year = "2009",

month = may,

doi = "10.1681/ASN.2008101028",

language = "English (US)",

volume = "20",

pages = "1103--1112",

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T1 - Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

AU - Appel, Gerald B.

AU - Contreras, Gabriel

AU - Dooley, Mary Anne

AU - Ginzler, Ellen M.

AU - Isenberg, David

AU - Jayne, David

AU - Li, Lei Shi

AU - Mysler, Eduardo

AU - Sánchez-Guerrero, Jorge

AU - Solomons, Neil

AU - Wofsy, David

AU - Abud, Carlos

AU - Adler, Sharon

AU - Alarcón, Graciela

AU - Albuquerque, Elisa

AU - Almeida, Fernando

AU - Alvarellos, Alejandro

AU - Appel, Gerald

AU - Avila, Hilario

AU - Blume, Cornelia

AU - Boletis, Ioannis

AU - Bonnardeaux, Alain

AU - Braun, Alan

AU - Buyon, Jill

AU - Cervera, Ricard

AU - Chen, Nan

AU - Chen, Shunle

AU - Da Costa, António Gomes

AU - Davids, Razeen

AU - D'Cruz, David

AU - De Ramón, Enrique

AU - Deodhar, Atul

AU - Doria, Andrea

AU - Dussol, Bertrand

AU - Emery, Paul

AU - Fiechtner, Justus

AU - Floege, Jürgen

AU - Fragoso-Loyo, Hilda

AU - Furie, Richard

AU - Ghazalli, Rozina

AU - Ghossein, Cybele

AU - Gilkeson, Gary

AU - Ginzler, Ellen

AU - Gordon, Caroline

AU - Grossman, Jennifer

AU - Gu, Jieruo

AU - Guillevin, Loïc

AU - Hatron, Pierre Yves

AU - Herrera, Gisela

AU - Hiepe, Falk

AU - Houssiau, Frederic

AU - Hübscher, Osvaldo

AU - Hura, Claudia

AU - Kaplan, Joshua

AU - Kirsztajn, Gianna

AU - Kiss, Emese

AU - Kutty, Ghazali Ahmad

AU - Laville, Maurice

AU - Lazaro, Maria

AU - Lenz, Oliver

AU - Li, Leishi

AU - Lightstone, Liz

AU - Lim, Sam

AU - Malaise, Michel

AU - Manzi, Susan

AU - Marcos, Juan

AU - Meyer, Olivier

AU - Monge, Pablo

AU - Naicker, Saraladev

AU - Neal, Nathaniel

AU - Neuwelt, Michael

AU - Nicholls, Kathy

AU - Olsen, Nancy

AU - Ordi-Ros, Jose

AU - Ostrov, Barbara

AU - Pestana, Manuel

AU - Petri, Michelle

AU - Pokorny, Gyula

AU - Pourrat, Jacques

AU - Qian, Jiaqi

AU - Radhakrishnan, Jai

AU - Rovin, Brad

AU - Roman, Julio Sanchez

AU - Shanahan, Joseph

AU - Shergy, William

AU - Skopouli, Fotini

AU - Spindler, Alberto

AU - Striebich, Christopher

AU - Sundel, Robert

AU - Swanepoel, Charles

AU - Si, Yen Tan

AU - Tate, Guillermo

AU - Tesaŕ, Vladimír

AU - Tikly, Mohamed

AU - Wang, Haiyan

AU - Yahya, Rosnawati

AU - Yu, Xueqing

AU - Zhang, Fengchun

AU - Zoruba, Diana

PY - 2009/5

Y1 - 2009/5

N2 - Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

AB - Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

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Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

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