LOWER INCIDENCE OF HYPOCALCEMIA IN HEMODIALYSIS PATIENTS RECEIVING EVOCALCET COMPARED WITH ETELCALCETIDE: A MULTICENTER COHORT STUDY (MBD-NEXT)

Calcimimetics (CM) lower parathyroid hormone leading to reduced serum calcium (Ca) levels in hemodialysis patients. Comparative data of evocalcet (EVO) with etelcalcetide (ETE) is limited. EVO has a much shorter effective half-life than ETE in hemodialysis patients. We compared the risk of hypocalcemia, subsequent dose reduction or discontinuation of CM, and recovery to normocalcemia across these agents.

In this prospective MBD-NEXT cohort (January 2017– June 2022), we enrolled Japanese maintenance hemodialysis patients who had serum phosphate levels ≥3.5 mg/dL or were prescribed any phosphate binders at least once before the administration of EVO or ETE. We defined each person-period as starting at the first prescription of EVO or ETE. Each person-period ended at the earliest occurrence of any of the following: a switch to another CM, a lapse of 90 days since the last CM prescription, initiation of any bone-modifying agent, hospital transfer, death, or the end of the study period. Patients could start another person-period. The primary endpoint was incident moderate/severe hypocalcemia (corrected Ca levels <8.0 mg/dL). Patients were classified into four groups: CM-naïve patients initiated on EVO (naïve-EVO), or on ETE (naïve-ETE), patients previously treated with any CM and switched to EVO (switch-EVO), or to ETE (switch-ETE). For time-to-event analyses, we  fitted shared-frailty Cox regression models with patient as a shared parameter. We compared trajectories of PTH between EVO and ETE using a mixed effects model and the time to recovery to normocalcemia (≥8.4 mg/dL) using cumulative incidence curves . We also compared dose reduction or discontinuation of CM following the primary endpoint.

Among 3,418 patients screened, 3,325 contributed 3,988 person-periods. The primary endpoint was reached by 52 weeks in 26.2%, 37.0%, 12.0%, and 22.6% of patients in the naïve-EVO (n=992), naïve-ETE (1035), switch-EVO (991), and switch-ETE (786) groups, respectively (Table 1). We observed a slightly steeper decline of PTH in ETE users than in EVO users (p <0.001). In adjusted Cox models, the hazard ratios (HRs) for the primary endpoint were 4.35 (95% CI, 3.25–5.81) for naïve-EVO, 7.76 (95% CI, 5.83–10.33) for naïve-ETE, and 4.19 (95% CI, 3.10–5.66) for switch-ET as compared to the switch-EVO group (Table 2). The between-drug differences were attenuated after adjustment for time-dependent PTH levels. Higher baseline corrected Ca levels (HR, 0.24; 95% CI, 0.20–0.28) and higher IV-VDRA doses (HR, 0.76; 95% CI, 0.69–0.85 per 1 μg/week) were associated with a lower risk of hypocalcemia, whereas higher baseline alkaline phosphatase levelswas associated with a higher risk (HR, 1.46; 95% CI, 1.23–1.74 per doubling). The median time of recovery to normocalcemia was significantly longer in the CM-naïve groups than in prior CM users (median, 7.0 vs 4.0 days; p <0.001). Within four weeks after the endpoint, dose reduction or discontinuation of CM was more frequent with ETE (32.0% in naïve and 28.8% in switch groups) than with EVO (21.5% in naïve and 18.5% in switch groups).

Partly because of the slower decline of iPTH after EVO administration, EVO showed a lower risk of hypocalcemia than ETE, regardless of prior usage of any CM. In addition, recovery to normocalcemia was slower in the CM-naïve groups than in the switching groups.