Introduction:
Both cyclical cyclophosphamide (CYC) with corticosteroids (CS) and rituximab are recommended as first-line therapies for patients with primary membranous nephropathy (MN). However, the high doses of CYC and CS associated with this regimen raise significant concerns. Additionally, several retrospective studies suggest that a lower dose of CYC/CS may effectively induce remission in MN patients. Therefore, this study aimed to assess whether the lower dose of cyclical CYC/CS was non-inferior to the standard dose of CYC/CS in patients with MN.
Methods:
In this multicentric study, we randomly assigned 114 patients to receive either standard-dose CYC/CS or low-dose CYC/CS (prednisolone 0.5 mg/kg/day during months 1, 3, and 5, along with oral CYC 1-1.5 mg/kg/day during months 2, 4 and 6). The primary outcome was defined as complete (CR) or partial remission (PR) of proteinuria between months 6 and 24. (CTRI/2019/09/021287)
Results:
The median proteinuria was, mean serum albumin and creatinine levels were 6.83 g/day (interquartile range (IQR) 5.02, 10.15), 2.34 ± 0.59 g/dl and 0.92 ± 0.33 mg/dl, respectively. Eight-six (75.43%) patients had PLA2R-associated MN, with a median antibody titer of 161.5 (IQR 78.02, 305.30) RU/ml. The low-dose group achieved a 73% reduction in corticosteroid dosage and a one-third reduction in CYC dosage compared to the standard protocol. In the intention-to-treat assessment, 45 patients (78.94%) in the low-dose group and 50 patients (87.71%) in the standard-dose group achieved the primary outcome of any remission between months (risk difference, 8.78 percentage points, 95% CI -6.06,23.93%, p=0.20). The low-dose group demonstrated non-inferiority to the standard-dose group in achieving remission (z-statistic = 2.12, p = 0.017). CR was achieved by 22 (38.59%) patients in the low-dose group and 24 (42.10%) patients in the standard-dose group (risk difference, 3.5 percentage points, 95% CI -14.96,22.30%). Forty-five (78.94%) and 55 (96.49%) patients receiving the low-dose and standard-dose CYC/CS experienced at least one adverse event (p=0.008)).
Conclusions:
Low-dose CYC/CS is non-inferior to the standard dose of CYC/CS in achieving proteinuric remission in patients with MN. The reduced-dose cyclical CYC/CS regimen offers a feasible alternative, particularly in resource-limited settings.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.