Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial
Ellen M Ginzler, David Wofsy, David Isenberg, Caroline Gordon, Laura Lisk, Mary-Anne Dooley, ALMS Group, 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, Gabriel Contreras, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Atul Deodhar, Mary Anne Dooley, 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, Jorge Sanchez-Guerrero, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Si Yen Tan, Guillermo Tate, Vladimír Tesar, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba, Ellen M Ginzler, David Wofsy, David Isenberg, Caroline Gordon, Laura Lisk, Mary-Anne Dooley, ALMS Group, 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, Gabriel Contreras, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Atul Deodhar, Mary Anne Dooley, 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, Jorge Sanchez-Guerrero, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Si Yen Tan, Guillermo Tate, Vladimír Tesar, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba
Abstract
Objective: To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis.
Methods: Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5-1.0 gm/m(2)/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables.
Results: Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA-SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti-double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide.
Conclusion: In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis.
Trial registration: ClinicalTrials.gov NCT00377637.
Source: PubMed