etelcalcetide
Sources réglementaires consultées
Indications approuvées
- Hyperparathyroïdie secondaire chez l’adulte atteint de maladie rénale chronique sous hémodialyse.
Contre-indications
Absolues
- Calcium corrigé inférieur à la limite basse de la normale ou hypersensibilité.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer hypocalcémie, convulsions, allongement du QT et arythmie. Mesurer le calcium avant l’instauration, dans la semaine suivant l’instauration ou l’ajustement, puis toutes les 4 semaines. — CIMA/AEMPS, ficha técnica 1161142010
- Mise en garde majeure · Une suppression excessive de la PTH peut provoquer une maladie osseuse adynamique ; réduire ou interrompre si la PTH est <100 pg/ml. — CIMA/AEMPS, ficha técnica 1161142010
Interactions médicamenteuses
- SévèreCinacalcet, dénosumab ou autres traitements hypocalcémiants
Mécanisme: Ils augmentent le risque d’hypocalcémie ; ne pas associer l’ételcalcétide au cinacalcet.
Recommandation: Ne pas associer au cinacalcet et surveiller étroitement le calcium avec les autres traitements hypocalcémiants.
CIMA/AEMPS, ficha técnica 1161142010
Effets indésirables
Communs (≥1%)
Diminution du calcium, vomissements, spasmes musculaires, diarrhée et nausées
Rares mais graves
Hypocalcémie sévère, convulsions et arythmie ventriculaire
Grossesse et allaitement
Il est préférable de l’éviter pendant la grossesse. Pendant l’allaitement, décider d’interrompre l’allaitement ou le traitement.
Bibliographie récente (PubMed)
Chronic kidney disease is a common cardiovascular risk indicator and strongly associated with increased morbidity and mortality. The heart and kidneys are pathophysiologically closely connected, which becomes particularly obvious in patients with cardiorenal syndrome. This review summarizes clinically relevant studies on the cardio-renal interaction published in 2021 and 2022. Selected trials published in high-impact journals were chosen from the database Pubmed and included in this review. New evidence about the selective mineralocorticoid receptor antagonist finerenone and the renoprotective sodium-glucose co-transporter-2-inhibitors (SGLT2-Inhibitors) are discussed and we update on novel insights about the treatment of arterial hypertension in patients with severe chronic kidney disease with the thiazide-like diuretic chlorthalidone. Finally, data on infective endocarditis in patients on chronic hemodialysis and the treatment of secondary hyperparathyroidism with the calcimimetic drug etelcalcetide in patients with end stage kidney disease are critically reviewed. Several important studies investigating cardio-renal interactions were recently published may affect clinical practice. The graphical abstract (Fig. 1) depicts the most relevant clinical studies investigating cardio-renal interactions.
Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus produ
The impact of etelcalcetide on patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) has been studied since its introduction in 2016/2017. However, only a handful of studies reported clinically relevant outcomes. This narrative review aims to summarize the published data about etelcalcetide, focusing on biochemical, cardiovascular (CV) and bone endpoints, as well as adverse effects and all-cause mortality. A literature review of the use of etelcalcetide in hemodialysis patients with SHPT was conducted. Several sources were used, such as PubMed, Google Scholar and Cochrane Library. Regarding bone and mineral metabolism, etelcalcetide is effective in reducing serum levels of parathormone (PTH), calcium, phosphate and fibroblast growth factor 23 (FGF23). Preliminary data have highlighted its role in reducing bone turnover and improving mineralization and preservation of bone structure, indicating a possible positive impact on renal osteodystrophy. From a CV perspective, etelcalcetide is associated with a significant reduction in left ventricular hypertrophy. In addition, etelcalcetide reduces FGF23 and increases sclerostin serum levels. This data suggests a possible CV beneficial effect. Etelcalcetide is effective in controlling SHPT. Promising data is available for some bone and surrogate cardiovascular endpoints, suggesting a possible beneficial effect. There is a lack of studies specifically designed to evaluate its role in reducing fractures, CV and all-cause mortality.
Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. New-user design within prospective cohort. 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. Data are unavailable for provider dosing prot