Real-World Etelcalcetide Therapy for Secondary Hyperparathyroidism in Hemodialysis Patients with Inadequate Cinacalcet Response or Intolerance: Prospective Observational Study.

BACKGROUND: Cinacalcet is widely used for secondary hyperparathyroidism in hemodialysis (HD) patients. However, inadequate biochemical response, gastrointestinal intolerance, and pill burden may limit its use. Intravenous etelcalcetide offers an alternative in such cases. We aimed to provide real-world evidence on the effectiveness of etelcalcetide in reducing parathyroid hormone (PTH) levels and to assess the time to full response in HD patients with inadequate cinacalcet response or intolerance. METHODS: A prospective observational study was conducted among HD patients transitioned from cinacalcet to etelcalcetide because of inadequate response or intolerance. The primary outcome was change in serum PTH from baseline to three months. Secondary outcomes included time to full biochemical response (PTH 150-600 ng/mL), hypocalcemia calcium ≤2.0 mmol/L), and time to first hypocalcemia. Changes in PTH from baseline to three months were assessed using the Wilcoxon signed-rank test. Time-to-event outcomes were analyzed using Kaplan-Meier and multivariable Cox regression. RESULTS: A total of 146 patients (age 52± 16 years) were included. At three months, etelcalcetide reduced median (IQR) PTH from 936 (738-1257) pg/mL to 585 (394-962) pg/mL, p < 0.001. At the final assessment, 57% of patients achieved the target PTH range, with a median response time of 3 months. Higher baseline PTH was associated with a lower hazard of achieving full biochemical response (aHR = 0.88 per 100pg/mL increase, 95% CI: 0.83-0.93, p < 0.001). Hypocalcemia occurred in 71% of patients, with a median of 5 months. Higher baseline calcium (aHR 0.81 per 0.1-mmol/L increase, 95% CI 0.71-0.92, p = 0.002) and older age (aHR 0.97 per 1-year increase, 95% CI 0.96-0.99, p < 0.001) were associated with a lower hazard of hypocalcemia. CONCLUSIONS: Etelcalcetide use was associated with a significant PTH reduction and may provide a useful therapeutic option for HD patients with inadequate cinacalcet response or intolerance. However, hypocalcemia was common, underscoring the need for close monitoring and timely adjustment of etelcalcetide and concomitant therapies.