Influence of dialysate Ca concentrations on the therapeutic effects of etelcalcetide with concomitant drugs in patients with secondary hyperparathyroidism

Abstract

Aim Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs. Methods We performed post hoc analyses of a 52‐week, open‐label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses. Results There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60‐240 pg/mL, 8.4‐10.0 mg/dL and 3.5‐6.0 mg/dL, respectively) across the three groups. TRACP‐5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group. Conclusion The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment.

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan

“…As in the prior 52-week study [ 17 ], we found no differences in the efficacy and safety of etelcalcetide when patients were divided into subgroups according to their dialysate Ca concentration (Tables 3 and 5 ).…”

“…2), which might reflect a relationship between younger age and greater parathyroid gland sensitivity/PTH secretory potential [13][14][15][16], although this has yet to be confirmed in the context of SHPT. As in the prior 52-week study [17], we found no differences in the efficacy and safety of etelcalcetide when patients were divided into subgroups according to their dialysate Ca concentration (Tables 3 and 5).…”

Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial

“…Most of the dialysis units followed the JSDT guideline published in 2008 [ 25 ] and updated in 2013 accordingly [ 26 ]. Both cinacalcet and evocalcet are effective for controlling secondary hyperparathyroidism [ 27 ] irrespective of D-Ca [ 28 , 29 ]. By comparing the effects on serum calcification propensity (T50), a surrogate marker of calcification, Shoji T et al reported that a calcimimetic agent etelcalcetide was more effective than a vitamin D receptor activator maxacalcitol [ 30 ].…”