ORLANDO, Fla.— Starting the intravenous calcimimetic etelcalcetide at a low dose of 2.5 mg appears to be as safe and effective as starting at the standard 5 mg dose, according to new research presented at the National Kidney Foundation’s 2017 Spring Clinical Meetings.
In an open-label extension trial lasting 2 years, Geoffrey Block, MD, of Denver Nephrology in Denver, and colleagues compared the 2 starting doses of the medication. Initially, up to 250 patients with secondary hyperparathyroidism (SHPT) received 2.5 mg and up to 155 patients received 5 mg of the drug 3 times per week. Dosing was then titrated to a maximum of 15 mg to attain target parathyroid hormone levels (PTH) within 2 to 9 times the upper limit of the normal range for the assay. Overall, 5% of patients discontinued the drug due to adverse events (AEs). At the start of the extension trial, the average PTH level was 709.5 pg/mL in the low-dose group and 651.2 pg/mL in the standard-dose group.
At 6, 12, 18, and 24 months, PTH levels were maintained within target for 62%, 64%, 67%, and 81% of participants who started at 2.5 mg, respectively, and 63%, 70%, 68%, and 74% who started at 5 mg, respectively.
“The recommended starting dose of etelcalcetide is 5 mg TIW but the study showed that for individuals previously treated with either etelcalcetide or cinacalcet, regimens in which etelcalcetide was reinitiated or switched to 2.5 or 5 mg TIW maintained PTH and was well tolerated when targeting the KDIGO PTH range,” Dr Block and colleagues told Renal & Urology News. “However the generalizability of the results of this post hoc analysis is limited by the lack of randomization, the study not being designed to evaluate 2 doses, and the open-label nature of the study.”
To control hyperphosphatemia, phosphate levels needed to be kept at or below the upper limit of normal. A third or more of patients in both groups stayed within that target at 6, 12, and 18 months (40%, 39%, and 38% for the 2.5 mg group vs 33%, 33%, and 32% for the 5 mg group). Mean phosphorus levels for the 2.5 mg group and 5 mg group were 5.2 and 5.3 mg/dL, respectively.
Corrected serum calcium must be at or above the lower limit of normal before starting etelcalcetide to prevent hypocalcemia. Asymptomatic hypocalcemia occurred more frequently in patients switching to or initiating the 5 mg dose (30% of the 2.5 mg group vs 44% of the 5 mg group). About 1% of the 2.5 mg group experienced symptomatic hypocalcemia.
Serious treatment-related AEs occurred in 0.5% of the low-dose group and 0.4% of the standard-dose group. Discontinuation of etelcalcetide occurred in 4% and 2.7%, respectively.
The most common AEs were nausea, vomiting, sepsis, and upper abdominal pain. Serious adverse events rarely occurred but included pneumonia, sepsis, arteriovenous fistula thrombosis, cardiac arrest, and anemia.
The study was funded by Amgen, which manufactures etelcalcetide (Parsabiv). The investigators disclosed various financial relationships with the company.
See more coverage from the National Kidney Foundation Spring Clinical meeting.
Cheng S, Block G, Dehmel B, Deng H, and Chertow G. Analysis of a single-arm extension study evaluating etelcalcetide starting dose for treatment of secondary hyperparathyroidism in patients on hemodialysis. Poster presented at the National Kidney Foundation’s 2017 Spring Clinical Meetings in Orlando, Florida, April 18-22, 2017. Poster 187.