Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism

Abstract

Background and objectivesVitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T50 value than a vitamin D receptor activator maxacalcitol.Design, setting, participants, & measurementsA randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively.ResultsIn total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T50 value was changed from 116 minutes (interquartile range, 90–151) to 131 minutes (interquartile range, 102–176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98–174) to 166 minutes (interquartile range, 127–218) in the etelcalcetide group. The increase in T50 value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score.ConclusionsEtelcalcetide was more effective in increasing T50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs.Clinical Trial registry name and registration number:VICTORY; UMIN000030636 and jRCTs051180156

Emerging cross-talks between chronic kidney disease–mineral and bone disorder (CKD–MBD) and malnutrition–inflammation complex syndrome (MICS) in patients receiving dialysis

“…In contrast to VDRAs, calcimimetics generally lower serum levels of calcium, phosphate, FGF23, and CPPs. In a recent study that controlled serum PTH levels within the same range using maxacalcitol or etelcalcetide, T50 were significantly longer in the etelcalcetide group [117]. As represented by the results of the ADVANCE study and the EVOLVE trial, accumulating evidence has shown that calcimimetics provide better control of SHPT and reduce the risk of bone fractures, parathyroidectomy, VC, valve calcification, cardiovascular events, and death [118,119].…”

Impact of etelcalcetide on fibroblast growth factor‐23 and calciprotein particles in patients with secondary hyperparathyroidism undergoing haemodialysis

“…Interestingly, sevelamer was associated with reduced inflammation and improved vascular function in correlation with a reduction in CPP, 27 and the changes in CPPs were positively correlated with those in LDL cholesterol under use of lanthanum carbonate 26 . The etelcalcetide significantly prolonged CPP maturation time (T50) compared with vitamin D, 28 which means etelcalcetide has more advantageous suppressing calcification propensity than vitamin D. In our study, etelcalcetide failed to significantly reduce CPP compared to no use of etelcalcetide. In the correction of hypocalcaemia, loading calcium preparation significantly reduced CPP compared to loading active vitamin D. Our results suggest that calcium preparation may have an advantage in protecting vascular calcification for correction of consequent hypocalcaemia.…”

Prediction Model of Postoperative Severe Hypocalcemia in Patients with Secondary Hyperparathyroidism Based on Logistic Regression and XGBoost Algorithm

“…The SHPT is a common complication of maintenance dialysis patients, which can cause symptoms such as dialysis bone pain, pruritus, and insomnia and even significantly increase the fatality rate [ 17 ]. PTX is the most important treatment for patients with refractory SHPT [ 8 ].…”