Long-Term Study of Mycophenolate Mofetil as Continuous Induction and Maintenance Treatment for Diffuse Proliferative Lupus Nephritis

Abstract

Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamide followed by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated with less drug toxicity. Results from an extended long-term study, with median follow-up of 63 mo, that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented. Thirty-three patients were randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm, both in combination with prednisolone. More than 90% in each group responded favorably (complete or partial remission) to induction treatment. Serum creatinine in both groups remained stable and comparable over time. Creatinine clearance increased significantly in the MMF group, but the between-group difference was insignificant. Improvements in serology and proteinuria were comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up (P ‫؍‬ 0.667). Both the relapse-free survival and the hazard ratio for relapse were similar between MMF-and CTX-AZA-treated patients (11 and nine patients relapsed, respectively) and between those with MMF treatment for 12 or >24 mo. MMF treatment was associated with fewer infections and infections that required hospitalization (P ‫؍‬ 0.013 and 0.014, respectively). Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death (P ‫؍‬ 0.062 by survival analysis). It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients.

Updates on the Treatment of Lupus Nephritis

“…21 Several recent controlled trials, and subsequent meta-analyses, establish MMF as one of the recommended, first-choice regimens for inducing a remission in severe active proliferative lupus nephritis. [22][23][24][25][26][27] An initial report was a Chinese study of 42 patients randomized to receive either 12 months of oral MMF (2 g/d for 6 months followed by 1 g/d for 6 months) or 6 months of oral cyclophosphamide (2.5 mg/kg per day), followed by oral azathioprine (1.5 mg/kg per day) for 6 months. 22 Both groups received concomitant tapering doses of corticosteroids.…”

“…However, infection was now significantly less in the MMF group (13 versus 40%), and mortality was still entirely in the cyclophosphamide group. 23 A larger U.S. induction trial, reported 5 years later in a more diverse population (Ͼ50% African Americans), examined 140 patients with proliferative lupus nephritis or membranous lupus nephritis randomized to intravenous cyclophosphamide monthly pulses versus oral MMF up to 3 g daily, each in conjunction with a fixed tapering dose of corticosteroids as induction therapy over 6 months. 24 Although the study was powered as a noninferiority trial, complete remissions and complete plus partial remissions at 6 months were significantly more common in the MMF arm (52%) than the cyclophosphamide arm (30%).…”

Histologic deterioration and more flares: The case against azathioprine plus methylprednisolone in the treatment of proliferative lupus nephritis

“…Approaches aiming to reduce treatmentrelated adverse effects include limiting the dosage and/or duration of CYC treatment. The efficacy and tolerability of mycophenolate mofetil combined with prednisolone have been demonstrated in Chinese patients with class IV lupus nephritis, who showed a Ͼ90% response rate and a 6.3% incidence of serum creatinine doubling over a median followup of 63 months (13). Data from studies in the US, which included high-risk subjects such as African American and Hispanic patients, showed a higher response rate (though still suboptimal, at 52%) and a lower relapse rate with mycophenolate mofetil and prednisone, compared with CYC-based induction or maintenance treatment, respectively (6,14).…”

New and emerging treatments for lupus nephritis

“…Both induction periods were followed by maintenance with azathioprine (AZA), and the two groups had statistically Clinical trials performed over the past 10 years have now fi rmly established mycophenolate mofetil (MMF) as a legitimate fi rst-line alternative to CYC for induction therapy. [19][20][21][22][23] An early study randomized 42 Chinese patients to either MMF (2 g/d for 6 months and then 1 g/d for 6 months) or oral CYC (2.5 mg/kg/d for 6 months) followed by AZA (1.5 mg/kg/d for 6 months), with oral prednisolone used in both arms. Both the initial study and the report of its 5-year follow-up 20 showed statistically equivalent rates of complete remission, partial remission, and disease relapses between the two arms.…”

“…[19][20][21][22][23] An early study randomized 42 Chinese patients to either MMF (2 g/d for 6 months and then 1 g/d for 6 months) or oral CYC (2.5 mg/kg/d for 6 months) followed by AZA (1.5 mg/kg/d for 6 months), with oral prednisolone used in both arms. Both the initial study and the report of its 5-year follow-up 20 showed statistically equivalent rates of complete remission, partial remission, and disease relapses between the two arms. However, at 5 years, rates of infection were signifi cantly less in the MMF group (13% vs. 40%), and the only patients to reach end-stage renal disease or death were in the CYC group.…”