Patients with primary membranous nephropathy (PMN) fared better after treatment with alternating corticosteroid and an immunosuppressant, a researcher reported here.
In a trial of patients with PMN and persistent nephrotic syndrome, those on cyclical treatment with corticosteroid and cyclophosphamide had a 44% higher chance of achieving either complete or partial remission of nephrotic syndrome after 24 months — the study’s primary endpoint — versus those on sequential treatment with tacrolimus (Envarsus, Protopic, Astagraf) and rituximab (Rituxan, 84% vs 58%, relative risk 1.44, 95% CI 1.08-1.92), according to Gema Fernandez Juarez, MD, PhD, of the Hospital Universitario Fundacion Alcorcón in Madrid.
Additionally, 60% of patients on corticosteroid and cyclophosphamide achieved complete remission at 24 months versus 26% of those on tacrolimus and rituximab (RR 2.36, 95% CI 1.34-4.16).
“The occurrence of remission was also faster in the corticosteroids-cyclophosphamide; the difference in the number of remission being already significant at 3 months,” Fernandez Juarez explained during a presentation at the American Society of Nephrology virtual Kidney Week.
Specifically, 77% of people on corticosteroid and cyclophosphamide had an immunological response with significant reductions in ant-PLA2R levels after only 3 months versus 45% of those on tacrolimus and rituximab (P=0.03).
Furthermore, 92% on corticosteroid and cyclophosphamide displayed an immunological response after 6 months of treatment versus 70% of the tacrolimus-rituximab group (P=0.04).
However, from 12 months to 24 months after baseline, immunological responses were not significantly different between the groups.
“Most remissions were complete in the corticosteroids-cyclophosphamide group, while most remissions were partial in the tacrolimus-rituximab group,” she said, adding that “early immunological response was followed by clinical remission in the vast majority of patients, which confirms the usefulness of anti-PLA2R monitoring for a personalized treatment.”
The open-label trial included adult patients with an eGFR of 45 mL/min/1.73 m2 or higher and proteinuria defined as more than 4 grams in 24 hours without a decrease of more than 50% during the observational period. All patients also had hypoalbuminemia with albumin levels of 3.5 g/dL or less during the observational period.
A total of 43 patients were randomized to receive 6 months of cyclical treatment with corticosteroid and cyclophosphamide. This was selected based upon 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines for glomerulonephritis, which recommend 6 months of cyclical treatment of alternative alkylating agents — typically cyclophosphamide — in addition to corticosteroids for patients who are deemed to be at high risk for progression, Fernandez Juarez explained.
This group was compared with 43 other patients who received the calcineurin inhibitor tacrolimus at a full dose for 6 months, which was then tapered for another 3 months followed by sequential treatment with 1 gram of the monoclonal antibody rituximab at 6 months.
Fernandez Juarez pointed out that “calcineurin inhibitors — both cyclosporine and tacrolimus — have shown efficacy in inducing remission of nephrotic syndrome in about 70% of patients, but the main limitation of these drugs is the high rate of relapse after their discontinuation.”
Only 2.7% of patients in the corticosteroid-cyclophosphamide group experienced a relapse of symptoms versus 12% of those in the tacrolimus-rituximab group during the 24-month follow-up.
An overwhelming majority in each treatment group experienced any type of adverse event (AE): 98% in the corticosteroid-cyclophosphamide group and 91% in the tacrolimus-rituximab group. However, there were no fatal AEs, and the rate of serious nonfatal AEs were similar between the groups (19% in corticosteroid-cyclophosphamide vs 14% in tacrolimus-rituximab).
The study was funded by the government of Spain and supported by the Instituto Salud Carlos III, as well as the European Nephrology, Dialysis, and Transplantation Society.