INTRODUCTION AND AIMS: In the ongoing DUET trial, SPAR 200, 400, 800 mg/d resulted in greater reduction in proteinuria vs irbesartan (IRB) 300 mg/d over an 8-week double-blind (DB) period in patients with FSGS. Treatment with SPAR alone in an open-label extension (OLE) resulted in further decline in proteinuria over a total of 48 weeks. Because some patients received new IST during the OLE, further analyses were performed to determine whether IST contributed to the observed long-term benefits of SPAR.
METHODS: DUET patients were aged 8-75 years in the US or 18-75 years in the EU and had biopsy-proven FSGS, baseline (BL) urine protein/creatinine ratio (Up/C) ≥1 g/g, and estimated glomerular filtration rate (eGFR) >30 mL/min. In the OLE, patients randomized to DB treatment with SPAR continued (SPAR:SPAR) and those randomized to IRB were switched to SPAR (IRB:SPAR). Up/C, eGFR, and blood pressure (BP) were measured every 12 weeks to Week 48 and were compared with BL (Week 0 for SPAR:SPAR; Week 8 for IRB:SPAR). Data from all patients and from the remaining population after exclusion of patients who initiated new IST in the OLE were analyzed separately.
RESULTS: In the SPAR:SPAR group (n=50), SPAR resulted in rapid, sustained reduction in Up/C from BL (Table). Six (12%) SPAR:SPAR patients received IST during the OLE, which had no effect on Up/C decline. In the IRB:SPAR group (n=33), switching to SPAR resulted in significant reduction in Up/C (Week 16), which was sustained until the end of follow-up, suggesting additive effect of SPAR to IRB (Table). Similar to the SPAR:SPAR group, the IRB:SPAR group showed no effect of new IST (n=2; 6%) on Up/C decline. The proportion of patients reaching modified partial remission (Up/C ≤1.5 g/g and >40% decrease) was similar over the 48 weeks, regardless of IST use, in both the SPAR:SPAR and IRB:SPAR groups. Moreover, initiation of IST had no effect on the course of eGFR and BP in the SPAR:SPAR or IRB:SPAR group.
CONCLUSIONS: Sustained and progressive antiproteinuric effects of SPAR in primary FSGS associated with early BP reduction and stable eGFR over 48 weeks are not attributable to initiation of new IST.
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