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 receivemycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receivingmycophenolate 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. Copyright 2005 Massachusetts Medical Society.
RCT Entities:
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. Copyright 2005 Massachusetts Medical Society.
Authors: Rina Mina; Emily von Scheven; Stacy P Ardoin; B Anne Eberhard; Marilynn Punaro; Norman Ilowite; Joyce Hsu; Marisa Klein-Gitelman; L Nandini Moorthy; Eyal Muscal; Suhas M Radhakrishna; Linda Wagner-Weiner; Matthew Adams; Peter Blier; Lenore Buckley; Elizabeth Chalom; Gaëlle Chédeville; Andrew Eichenfield; Natalya Fish; Michael Henrickson; Aimee O Hersh; Roger Hollister; Olcay Jones; Lawrence Jung; Deborah Levy; Jorge Lopez-Benitez; Deborah McCurdy; Paivi M Miettunen; Ana I Quintero-del Rio; Deborah Rothman; Ornella Rullo; Natasha Ruth; Laura E Schanberg; Earl Silverman; Nora G Singer; Jennifer Soep; Reema Syed; Larry B Vogler; Ali Yalcindag; Cagri Yildirim-Toruner; Carol A Wallace; Hermine I Brunner Journal: Arthritis Care Res (Hoboken) Date: 2012-03 Impact factor: 4.794
Authors: A Rother; P Glander; E Vitt; D Czock; N von Ahsen; V W Armstrong; M Oellerich; K Budde; R Feneberg; B Tönshoff; L T Weber Journal: Eur J Clin Pharmacol Date: 2012-01-25 Impact factor: 2.953
Authors: Michael Look; Eric Stern; Qin A Wang; Leah D DiPlacido; Michael Kashgarian; Joe Craft; Tarek M Fahmy Journal: J Clin Invest Date: 2013-04 Impact factor: 14.808