(121) Mortality associated with use of etelcalcetide versus cinacalcet for the treatment of secondary hyperparathyroidism in patients in haemodialysis: a population based study in Lazio, Italy

Background: Secondary hyperparathyroidism is a clinically significant complication commonly present in chronic renal disease, and especially in patients in haemodialysis. Pharmacological therapy aims at reducing the level of parathyroid hormone. Among specific treatments, the long acting calcimimetic etelcalcetide has been authorised in Italy a few years ago based on results of clinical trials, whereas evidence on efficacy and safety in real world is scarce.

Objectives: The present study, conducted with funds from the Italian Medicines Agency (Pharmacovigilance call 2012-14), aims to perform a comparative evaluation of mortality associated to the use of the two calcimimetics etelcalcetide and cinacalcet in patients affected by secondary hyperparathyroidism and in chronic haemodialysis in a real world setting.

Methods: This observational study was based on data available in the Lazio Regional Dialysis and Transplantation Registry and information collected in an ad hoc survey in regional dialysis centres. A cohort of new users of cinacalcet and etelcalcetide in the years 2018-2020 was enrolled and followed from the day of first drug claim for a maximum of 365 days with an intention-to-treat approach. The study outcome was overall mortality, and in case of kidney transplantation the observation was censored. Mortality rates for 100 person-years (py) were calculated and a Cox regression model was applied to compare the outcome between users of etelcalcetide versus cinacalcet, adjusting for age, sex and a propensity score (PS) which was built through a stepwise backward procedure applied on the clinical baseline characteristics.

Results: Overall, 652 haemodialytic patients were enrolled, with 59% males and a mean age of 64 years. Among 500 new users of etelcalcetide and 152 of cinacalcet, 66 cases of deaths were registered during follow-up, yielding mortality rates of 9.9 per 100 py for etelcalcetide and of 13.4 per 100 py for cinacalcet. The raw Hazard Ratio (HR) of etelcalcetide vs cinacalcet was 0.74 (95%CI: 0.43–1.26). Adjusting first for age and sex, and second for age, sex and PS the HRs were 0.67 (95%CI: 0.39–1.14) and 0.55 (95%CI: 0.30–1.00), respectively.

Conclusions: The present study indicates a mortality reduction in patients treated with etelcalcetide respect to cinacalcet, with a borderline statistical significance. This preliminary analysis does not permit to draw final conclusion on efficacy and safety of etelcalcetide and will be repeated and empowered with an as-treated approach and considering a 24-month follow-up and additional clinically relevant outcomes.