Etelcalcetide Versus Cinacalcet for Secondary Hyperparathyroidism in Hemodialysis Patients: A Multicentre Comparison with 24 Months of Follow-Up

Abstract

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication of end-stage kidney disease. Although etelcalcetide has demonstrated short-term superiority over cinacalcet in randomized trials, real-world comparative data beyond 12 months remain scarce. This study compared the long-term effectiveness of etelcalcetide versus cinacalcet in hemodialysis patients over 24 months using propensity score matching. Methods: This multicenter retrospective study screened 457 hemodialysis patients across five centers in Türkiye. Propensity score matching on age, sex, hemodialysis vintage, and baseline intact parathyroid hormone (iPTH) yielded balanced cohorts of 21 versus 21 for 12-month and 14 versus 14 for 24-month analyses. The primary outcome was percentage change in iPTH from baseline (%ΔPTH). Secondary outcomes included responder rates, KDIGO target achievement, response trajectory classification, and depth-of-response analysis. Results: At 12 months, etelcalcetide achieved significantly greater iPTH reduction (%ΔPTH: −50.5 ± 25.6% vs. −29.7 ± 40.6%; p = 0.047), with effect sizes increasing from medium to medium–large at 24 months (Cohen’s d: −0.612 to −0.779). Sustained response (≥30% iPTH reduction at both timepoints) was significantly higher with etelcalcetide (78.6% vs. 28.6%; p = 0.021), as was deep response (≥75% reduction) at 24 months (57.1% vs. 14.3%; p = 0.046). At 24 months, etelcalcetide demonstrated significantly lower serum calcium (p = 0.015), calcium–phosphate product (p = 0.023), and superior phosphate target attainment (85.7% vs. 28.6%; p = 0.004). Inter-patient response variability was nearly three-fold lower with etelcalcetide (CV: 42% vs. 151%). Conclusions: Etelcalcetide provided significantly greater, more sustained, and more consistent iPTH suppression than cinacalcet over 24 months, with additional benefits in mineral metabolism control. These findings support etelcalcetide as a potent therapeutic option for SHPT in hemodialysis patients and warrant confirmation in larger prospective trials.