Randomized Controlled Trial on the Efficacy of Reduced-Dose Cyclical Corticosteroids and Cyclophosphamide in Primary Membranous Nephropathy.

INTRODUCTION

The use of cyclophosphamide with corticosteroids for the management of membranous nephropathy (MN) is associated with significant safety concerns. Several retrospective studies suggest that a lower dose may effectively induce remission in participants with MN. This randomized trial assessed whether the lower dose of cyclical cyclophosphamide/corticosteroids was noninferior to the standard dose in patients with MN.

METHODS

We randomly assigned 114 participants (32 women and 82 men) to receive either the low dose (prednisolone, 0.5 mg/kg/d during months 1, 3, and 5 along with oral cyclophosphamide, 1.0-1.5 mg/kg/d during months 2, 4, and 6) or the standard-dose cyclophosphamide/corticosteroids (methylprednisolone, 1 g/d for 3 days, followed by prednisolone, 0.5 mg/kg/d during months 1, 3, and 5, along with oral cyclophosphamide, 2.0-2.5 mg/kg/d during months 2, 4, and 6). The primary outcome was complete remission (CR) or partial remission (PR) of proteinuria between months 6 and 24.

RESULTS

A total of 57 participants were randomized into each group. The mean age was 41.53 ± 12.29 years; median proteinuria, mean serum albumin, and creatinine levels were respectively 6.83 g/d (interquartile range: 5.02-10.15), 2.34 ± 0.58 g/dl, and 0.92 ± 0.26 mg/dl and were comparable between groups. In the intention-to-treat (ITT) analysis, 45 participants (78.94%) in the low-dose group and 50 participants (87.71%) in the standard-dose group achieved the primary outcome (treatment difference: -8.78%, 97.5% confidence interval [CI]: lower limit -22%) and met the criteria for noninferiority (P = 0.009). Forty-five (78.94%) and 55 (96.49%) participants receiving the low-dose and standard-dose cyclophosphamide/corticosteroids, respectively, experienced at least 1 adverse event (difference: -17.54%, 97.5% CI: lower limit -29.1%).

CONCLUSION

The results suggest that low-dose cyclophosphamide/corticosteroids may be as effective as the standard dose of cyclical cyclophosphamide/corticosteroids in achieving proteinuria remission in MN.