Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis

Ellen M. Ginzler, Mary Anne Dooley, Cynthia Aranow, Mimi Y. Kim, Jill Buyon, Joan T. Merrill, Michelle Petri, Gary S. Gilkeson, Daniel J. Wallace, Michael H. Weisman, Gerald B. Appel

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. METHODS: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. RESULTS: Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. CONCLUSIONS: In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.

Original languageEnglish (US)
Pages (from-to)2219-2228
Number of pages10
JournalNew England Journal of Medicine
Volume353
Issue number21
DOIs
StatePublished - Nov 24 2005

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Mycophenolic Acid
Lupus Nephritis
Cyclophosphamide
Intention to Treat Analysis
Body Surface Area
Diarrhea
Adrenal Cortex Hormones
Hospitalization
Maintenance
Confidence Intervals
Kidney
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ginzler, E. M., Dooley, M. A., Aranow, C., Kim, M. Y., Buyon, J., Merrill, J. T., ... Appel, G. B. (2005). Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. New England Journal of Medicine, 353(21), 2219-2228. https://doi.org/10.1056/NEJMoa043731

Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. / Ginzler, Ellen M.; Dooley, Mary Anne; Aranow, Cynthia; Kim, Mimi Y.; Buyon, Jill; Merrill, Joan T.; Petri, Michelle; Gilkeson, Gary S.; Wallace, Daniel J.; Weisman, Michael H.; Appel, Gerald B.

In: New England Journal of Medicine, Vol. 353, No. 21, 24.11.2005, p. 2219-2228.

Research output: Contribution to journalArticle

Ginzler, EM, Dooley, MA, Aranow, C, Kim, MY, Buyon, J, Merrill, JT, Petri, M, Gilkeson, GS, Wallace, DJ, Weisman, MH & Appel, GB 2005, 'Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis', New England Journal of Medicine, vol. 353, no. 21, pp. 2219-2228. https://doi.org/10.1056/NEJMoa043731
Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. New England Journal of Medicine. 2005 Nov 24;353(21):2219-2228. https://doi.org/10.1056/NEJMoa043731
Ginzler, Ellen M. ; Dooley, Mary Anne ; Aranow, Cynthia ; Kim, Mimi Y. ; Buyon, Jill ; Merrill, Joan T. ; Petri, Michelle ; Gilkeson, Gary S. ; Wallace, Daniel J. ; Weisman, Michael H. ; Appel, Gerald B. / Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. In: New England Journal of Medicine. 2005 ; Vol. 353, No. 21. pp. 2219-2228.
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abstract = "BACKGROUND: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. METHODS: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. RESULTS: Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. CONCLUSIONS: In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.",
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AU - Ginzler, Ellen M.

AU - Dooley, Mary Anne

AU - Aranow, Cynthia

AU - Kim, Mimi Y.

AU - Buyon, Jill

AU - Merrill, Joan T.

AU - Petri, Michelle

AU - Gilkeson, Gary S.

AU - Wallace, Daniel J.

AU - Weisman, Michael H.

AU - Appel, Gerald B.

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N2 - BACKGROUND: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. METHODS: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. RESULTS: Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. CONCLUSIONS: In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.

AB - BACKGROUND: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. METHODS: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. RESULTS: Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. CONCLUSIONS: In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.

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