Aim of the study. The treatment of secondary hyperparathyroidism is one of the main tasks in the correction of mineral and bone disorders (MBD) in patients with chronic kidney disease (CKD). However, the results of therapy for secondary hyperparathyroidism are still unsatisfactory. In our prospective randomized controlled trial were evaluated the effect and safety of 26 weeks of treatment with etelcalcetide (intravenous route of administration) compare with cinacalcet (oral administration) on CKD-MBD parameters in patients on program hemodialysis with secondary hyperparathyroidism.
Material and methods. The study group included 50 stable patients receiving hemodialysis with secondary hyperparathyroidism (PTH—300 pg/ml) and corrected Ca level greater than 2.2 mmol/L, who were randomized in a 1:1 ratio for treatment with etelcalcetide (n=25) or cinacalcet (n=25) for 26 weeks. All patients were monthly evaluated the levels of P, Ca, intact parathyroid hormone (IPTH), alkaline phosphatase (ALP); the levels of FGF 23, Klotho protein and sclerostin were assessed once in 3 months. The dose of both drugs was adjusted according to the serum iPTH level. The nature, frequency, and severity of treatment-emergent adverse events (AEs) were assessed.
Results. Therapy with cinacalcet and etelcalcetide led to a significant decrease in the level of iPTH in the blood serum from 613.1±235.1 to 302.2±205.1pg/ml (p<0.01) and from 718,2±272,3 to 320,1±292,5pg/ml (p<0.01), by 50,2% and 55,4%, respectively, by the end of the study. A significant decrease in the levels of corrected Ca was noted in both groups: in the etelcalcetide group from 2.25±0.12 to 2.06±0.18 mmol/l (p<0.05), in the cinacalcet group from 2.23±0.12 to 2.04±0.21 mmol/l (p<0.05). There was no significant change in the P levels. The alkaline phosphatase level significantly decreased in the cinacalcet group (from 178.7±116.8 to 78.9±34.1 U/L; p<0.05) and in the etelcalcetide group (from 170.3±115.7 to 75.8±30.8 U/L; p<0.05). There was a significant increase in Klotho protein levels by the end of the study from 17.9±5.0 to 57.1±9.3 (p<0.05) and from 17.6±3.7 to 91.6±16.2 pg/ml (p<0.05), respectively, in the cinacalcet and etelcalcetide groups. Changes in FGF-23 and sclerostin by 6 months reached statistically significant changes only in the etelcalcetide group, a decrease from the FGF-23 level from 42.7±12.2 to 23.0±12.3pg/ml and an increase in the level of sclerostin from 1, 59±0.31 to 2.20±0.33 ng/ml (p<0.05). During the study, 2 patients in the cinacalcet group dropped out due to dyspeptic symptoms and 1 patient in the etelcalcetide group dropped out due to hypocalcemia.
Conclusion. Etelcalcetide and cinacalcet are effective PTH-lowering drugs with a comparable safety profile. Treatment with etelcalcetide, in contrast to cinacalcet, was associated with significant increases in sclerostin and decreases in FGF-23, which may have beneficial effects on outcomes and requires further study.