D2- Gil Legarda and Joanalyn Balino
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
This research study is carried out in a randomized, open-label, parallel-group, multicenter study design. This research study was conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. There are 460 patients included the study and undergone into screening and another 370 patients who were randomly assigned. The researcher used a stratified randomization. Patients were randomly assigned to treatment with MMF or IVC by central, computerized, interactive voice response system. Patients excluded were based on treatment with MMF or IVC within the previous year, continous dialysis for less than 2 weeks before randomization or anticipated duration longer than 8 weeks, gastrointestinal hemorrhage within 6 months, pancreatitis, active peptic ulcer within three months, sever viral infection, severe cardiovascular disease, bone marrow insufficiency with cytopenias. The subjects were from the 88 centers in 20 countries in North America, Latin America, Asia, Australia, and Europe. Patients aged 12 to 75 yr and had a diagnosis of SLE by the American College of Rheumatology. Primary end point analysis was used on the intention to treat population. The odds ratios wer calculated by the use of logistic regression models for response. Models included a term for treatment group & covariates of race: asian, white or other; class of the disease, and location: United States/ Canada, Asia, Latin America, or rest of world. The response was defined as a decrease in urine creatinine/protein ratio, calculated from a 24 hours urine collection, to greater than 3 in patients with baseline nephritic range Cr/P equal or less than 3 or by less than or equal to 50 % in patients with subnephrotic baseline Cr/P greater than 3, and stabilization equal to 25 % or improvement in serum creatinine at 24 weeks as adjucated by a blinded clinical endpoints committee.
There are 460 patients screened, and 370 were randomly assigned. 6 randomly assigned patients one in the MMF group and 5 in the IVC group were excluded from the safety analysis because they received no study drug. At 24th week 306 or 82.7% patients remained in the research study. In the MMF group there were 35 subjects withdrew from the research study. Compared with 29 subjects in IVC group. The median dosage is 2.6 g/d for the 179 patients in the MMF; the median average dosage calculated was 2.6 g/l in white; 2.6 g/g in Asian, 2.4 g/d in black and 2.8 g/d in others. In this research study MMF did not show a superiority over IVC for the induction therapy of LN, a measurement by renal response rate after 24 weeks of treatment, 95% CI 0.8 to 1.8. Captivatingly, There was a statistical significant interaction between race and treatment group and between region and treatment group and region.
Even though meta analysis of smaller studies have recommended that more patients responded to MMF than IVC, results from the large and racially diverse population of this study indicate that these drugs in combination with prednisone have similar efficacy in short term induction therapy.
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 (2009). Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis. Journal of the American Society of Nephrology. Vol 20, pages 1103-1112. Retrieved June 24, 2009 from http://jasn.asnjournals.org/cgi/reprint/20/5/1103?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=5000&resourcetype=HWCIT