Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Abstract

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m 2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients

“…IT overall efficacy (CR plus PR) turned to be 84.8%, with the rate of CR 35.3%, which is similar to Chen et al data [15] and higher than the ALMS study [17], probably because our study group included not only patients with LN lass III–V but also milder cases. Under ST, the rate of flares turned to be 19.2% during median follow-up of 12 [1; 236] months, similar to the data from the long-term follow-up of the MAINTAIN Nephritis Trial [18].…”

“…Under ST, the rate of flares turned to be 19.2% during median follow-up of 12 [1; 236] months, similar to the data from the long-term follow-up of the MAINTAIN Nephritis Trial [18]. We did not specifically address the issue of different immunosuppression regimens efficacy in this study, but the general clinical assessment does not suggest benefits of MPA over CY and AZA in our group of patients, which is in agreement with the findings from ALMS study and long-term follow-up of the MAINTAIN Nephritis Trial [17, 18]. …”

Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus

“…The standard treatment for proliferative LN involves three to six months of induction therapy with either MMF or cyclophosphamide 24– 27 . Maintenance therapy can last for years, and the optimal duration of maintenance therapy is unknown.…”

“…Furthermore, the complex nature of SLE and the need to treat high-risk patients with established drugs has made it particularly difficult to evaluate new drugs. Treatment response is usually based on urine protein and serum creatinine measurements, and the cutoffs used to define complete and partial responses differ among trials 24, 27, 84 . New diagnostic methods – particularly companion diagnostics for biologic therapies – will facilitate the evaluation of new drugs.…”

Disparities in renal replacement in lupus nephritis: Current practice and future implications

“…The disparities in development of LN in predominantly US minority populations cannot be completely explained by differences in access to care alone. Poorer response to traditional therapy with intravenous cyclophosphamide has been reported in African American patients (17,18). Once nephritis is present, studies have shown a greater likelihood of progression to ESRD among African American and Hispanic patients than whites (19).…”