Switching patients from cinacalcet to etelcalcetide: evaluation of predictors of efficacy in a retrospective cohort study

BACKGROUND: The prevalence of SHPT depends on control strategy and target level of PTH. There is insufficient data for a justified choice of goals and strategy for the SHPT correction.

AIM: A retrospective, multicenter, cohort study was conducted to assess the ethelcalcetide efficacy after six months in real world practice. The study sought to identify whether MBD-CKD characteristics are predictive of achieving the goals.

MATERIALS AND METHODS: A study included 302 patients in 20 dialysis units in St. Petersburg. The primary endpoint was the proportion of patients who reached the target of PTH (300–599 pg/ml). The secondary endpoint was an absolute and relative decrease in PTH. The results were compared in subgroups with PTH (<600, 600–1000, ≥1000 pg/ml) and with and without signs of parathyroid authonomy.

RESULTS: In patients aged 56 (12) years (men — 61%) with a dialysis duration of 36 (Q1-Q3 23-55) months with baseline PTH level of 729 (548–957) pg/ml and with calcemia and phosphatemia 2.35 (0.25) and 1.97 (0.47) mM/L, the proportion of success was 49.7%. It is more expected for the PTH of 600–1000 pg/ml compared with PTH>1000 pg/ml: 79% vs. 36%, p<0.001. In presence of signs of parathyroid authonomy, 48% reached the target range vs. 86% in its absence (p<0.001) in subgroup with PTH of 600–1000 pg/ml. For patients with PTH above 1000 pg/ml, the proportion was 25% vs. 58% (p=0.016). The signs of parathyroid authonomy was the most significant independent risk for target achieving (OR=0.3 [95% CI 0.13; 0.68], p=0.004)

CONCLUSION: When transferring patients from cinacalcet to etelcalcetide, no new side effects or drug intolerance were noted. In moderate SHPT (PTH 600–1000 pg/ml) it is possible to achieve the target in most patients, but with higher level, the result worsened. The signs of parathyroid authonomy predicts the insufficient effect better than high baseline PTH level.

1. Sharma S, Gupta A. Adynamic bone disease: Revisited. Nefrologia (Engl Ed). 2022;42(1):8-14. doi: https://doi.org/10.1016/j.nefroe.2022.03.005

2. Elkhouli E, Nagy E, Santos CGS et al. Mixed uremic osteodystrophy: an ill-described common bone pathology in patients with chronic kidney disease. Osteoporos Int. 2023;34(12):2003-2012. doi: https://doi.org/10.1007/s00198-023-06886-5

3. Bernardor J, De Mul A, Bacchetta J, Schmitt CP. Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients. Curr Osteoporos Rep. 2023;21(2):193-204. doi: https://doi.org/10.1007/s11914-023-00782-x

4. Izzo C, Secondulfo C, Bilancio G et al. Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview. Life (Basel). 2024;14(3):418. doi: https://doi.org/10.3390/life14030418

5. Ketteler M, Evenepoel P, Holden RM; Conference Participants. Chronic kidney disease-mineral and bone disorder: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2025;107(3):405-423. doi: https://doi.org/10.1016/j.kint.2024.11.013

6. Liu Y, Yang Q, Chen G, Zhou T. A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease. Curr Pharm Des. 2022;28(40):3289-3304. doi: https://doi.org/10.2174/1381612829666221027110656

7. Liu X, Liu Y, Zheng P, Xie X, Li Z, Yang R, Jin L, Mei Z, Chen P, Zhou L. Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis. Eur J Clin Pharmacol. 2024;80(10):1555-1569. doi: https://doi.org/10.1007/s00228-024-03730-5

8. Khan BA, Qu X, Hua Y, Javaid MM. Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore. Cureus. 2023;15(11):e48186. doi: https://doi.org/10.7759/cureus.48186

9. Karaboyas A, Muenz D, Fuller DS et al. Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients. Am J Kidney Dis. 2022;79(3):362-373. doi: https://doi.org/10.1053/j.ajkd.2021.05.020

10. Karaboyas A, Muenz D, Hwang Y et al. Etelcalcetide Versus Cinacalcet in Hemodialysis Patients in the United States: A Facility Calcimimetic Approach to Assess Real-World Effectiveness. Kidney Med. 2022;4(6):100475. doi: https://doi.org/10.1016/j.xkme.2022.100475

11. on-line kal’kulyator veroyatnosti dostizheniya celevogo diapazona paratgormona (300-600 pg/ml). (In Russ.) Доступно по: https://parshinaev.shinyapps.io/PTH_lowering_with_etelcalcetide/. Ссылка активна 29.03.25

12. Martín-Carro B, Navarro-González JF, Ortiz A et al. Mineral and bone metabolism markers and mortality in diabetic patients on haemodialysis. Nephrol Dial Transplant. 2023;38(11):2589-2597. doi: https://doi.org/10.1093/ndt/gfad122

13. Fernández-Martín JL, Martínez-Camblor P, Dionisi MP et al. Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study. Nephrol Dial Transplant. 2015;30(9):1542-51. doi: https://doi.org/10.1093/ndt/gfv099

14. Lamina C, Kronenberg F, Stenvinkel P et al. Association of changes in bone mineral parameters with mortality in haemodialysis patients: insights from the ARO cohort. Nephrol Dial Transplant. 2020;35(3):478-487. doi: https://doi.org/10.1093/ndt/gfz060

15. Cozzolino M, Shilov E, Li Z, Fukagawa M et al. Pattern of Laboratory Parameters and Management of Secondary Hyperparathyroidism in Countries of Europe, Asia, the Middle East, and North America. Adv Ther. 2020;37(6):2748-2762. doi: 1 https://doi.org/0.1007/s12325-020-01359-1

16. Fusaro M, Barbuto S, Gallieni M et al. Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices. Clin Kidney J. 2023;17(1):sfad290. doi: https://doi.org/10.1093/ckj/sfad290

17. Block GA, Bushinsky DA, Cunningham J et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials. JAMA. 2017;317(2):146-155. doi: https://doi.org/10.1001/jama.2016.19456

18. Block GA, Bushinsky DA, Cheng S et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017;317(2):156-164. doi: https://doi.org/10.1001/jama.2016.19468

19. EVOLVE Trial Investigators; Chertow GM, Block GA, Correa-Rotter R et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482-94. doi: https://doi.org/10.1056/NEJMoa1205624

20. Zemchenkov A. How has EVOLVE evolved. Single study review. Nephrology and Dialysis. 2017;19(3):342-358. (in Russ)

21. Bernardor J, De Mul A, Bacchetta J, Schmitt CP. Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients. Curr Osteoporos Rep. 2023;21(2):193-204. doi: https://doi.org/10.1007/s11914-023-00782-x

22. Goto S, Hamano T, Fujii H et al. Hypocalcemia and cardiovascular mortality in cinacalcet users. Nephrol Dial Transplant. 2024;39(4):637-647. doi: https://doi.org/10.1093/ndt/gfad213

23. Block GA, Bushinsky DA, Cunningham J et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials. JAMA. 2017;317(2):146-155. doi: https://doi.org/10.1001/jama.2016.19456

24. Block GA, Bushinsky DA, Cheng S et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017;317(2):156-164. doi: https://doi.org/10.1001/jama.2016.19468

25. Shutov EV, Kotlyarova GV, Lysenko KM et al. Efficacy and safety of etelcalcetide compared with cinacalcet in patients received hemodialysis with secondary hyperparathyroidism. Results from a prospective randomized trial. Clinical Nephrology. 2021;(2):30-34. (in Russ). doi: https://doi.org/10.18565/nephrology.2021.2.34-40

26. Khairallah P, Cherasard J, Sung J et al. Changes in Bone Quality after Treatment with Etelcalcetide. Clin J Am Soc Nephrol. 2023;18(11):1456-1465. doi: https://doi.org/10.2215/CJN.0000000000000254

27. Dörr K, Kammerlander A, Lauriero F et al. Effect of etelcalcetide versus alfacalcidol on left ventricular function and feature-tracking cardiac magnetic resonance imaging in hemodialysis-a post-hoc analysis of a randomized, controlled trial. J Cardiovasc Magn Reson. 2023;25(1):62. doi: https://doi.org/10.1186/s12968-023-00975-4

28. Fernández-Villabrille S, Martín-Carro B, Martín-Vírgala et al. Novel Biomarkers of Bone Metabolism. Nutrients. 2024;16(5):605. doi: https://doi.org/10.3390/nu16050605

29. Freitas P, Pereira L. Etelcalcetide: What we know eight years since its approval. Nefrologia (Engl Ed). 2025;45(2):116-134. doi: https://doi.org/10.1016/j.nefroe.2025.01.010

30. Stephens JM, Fox KM, Desai P et al. Calcimimetic use in US hemodialysis facilities in first 2 years after the launch of etelcalcetide: A descriptive analysis of real-world clinical practice and outcomes. Hemodial Int. 2022;26(2):243-254. doi: https://doi.org/10.1111/hdi.12996

31. Karaboyas A, Zhao J, Ma J et al. Incorporation of Calcimimetics into ESRD Bundle: Changes in Etelcalcetide Utilization and PTH Control Following End of TDAPA Designation. Clin J Am Soc Nephrol. 2024. doi: https://doi.org/10.2215/CJN.0000000583

32. Disthabanchong S, Kasempin P, Srisuwarn P et al. The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data. PLoS One. 2024;19(5):e0304649. doi: https://doi.org/10.1371/journal.pone.0304649

33. Xipell M, Montagud-Marrahi E, Rubio MV et al. Improved Control of Secondary Hyperparathyroidism in Hemodialysis Patients Switching from Oral Cinacalcet to Intravenous Etelcalcetide, Especially in Nonadherent Patients. Blood Purif. 2019;48(2):106-114. doi: https://doi.org/10.1159/000496562