Mycophenolate mofetil compared with intravenous cyclophosphamide in the treatment of lupus nephritis: predictors of response.

BACKGROUND: The large, multinational Aspreva Lupus Management Study (ALMS) aimed to show the superiority of mycophenolate mofetil (MMF) compared with the National Institutes of Health pulsed intravenous cyclophosphamide (IVC) regimen in the induction of renal response. OBJECTIVES: To identify predictors of response to MMF or IVC therapy among patients with lupus nephritis. METHODS: Renal response to treatment was a defined reduction in the protein/creatinine ratio and a stable or reduced serum creatinine concentration. Markers of disease activity were evaluated in a post hoc subgroup analysis to determine if baseline values could be used to predict response to treatment. Patients were categorized into the following subgroups: hypocomplementemia or normal complement, defined as C3 <90 or ≥90 mg/dL and C4 <16 or ≥16 mg/dL; anti-dsDNA antibody titre (<30, 30-60, >60-200 or >200 IU/mL); and glomerular filtration rate (GFR) (<15, 15-29, 30-<60, 60-<90 or ≥90 mL/min/1.73m2). The number and percentage of responders and non-responders were calculated for each subgroup, by treatment and for both treatments combined, using a Cochran-Mantel-Haenszel Test. RESULTS: A total of 370 patients were randomized to receive MMF or IVC, each in combination with a defined prednisone taper (starting at ≤60 mg/day). The primary endpoint of the study was not met in that MMF did not produce a higher response rate than IVC. The response rates were: 104/185 (56.2%) in patients receiving MMF compared with 98/185 (53.0%) in patients receiving IVC (odds ratio=1.2; 95% confidence interval [CI]: 0.8, 1.8; p=0.58). The C3 concentration at baseline was not predictive of response, with a similar number of responders in each subgroup (odds ratio=0.8; 95% CI: 0.5, 1.3; p=0.46). Patients with a baseline C4 concentration of <16 mg/dL were more likely to respond to therapy than those with a C4 concentration of ≥16 (odds ratio=0.6; 95% CI: 0.4, 0.9; p=0.02). The anti-dsDNA antibody titre did not predict response (p=0.43). There was an effect of GFR subgroup on response (p<0.0001); a baseline GFR of <30 mL/min/1.73m2 was associated with the poorest response rate in both treatment groups (<25%); patients with moderate renal impairment (GFR 30-59 mL/min/1.73m2) had the greatest likelihood of response (>60% in both treatment groups). There were no differences observed between treatments in the outcomes reported. CONCLUSION: The renal response rate was comparable between treatment groups, thus the primary objective of the study was not met. Although this post hoc analysis of possible predictors was not powered to detect a difference in outcome between disease marker subgroups, a number of differences were observed. Though it is often suggested that IVC might be the treatment of choice in patients with a low GFR at baseline (<30 mL/min/1.73m2), there was no indication from ALMS that the response rates with IVC were better than those for MMF in this category, although the numbers were small.