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Cinacalcet maintained normocalcemia, reduced parathyroid hormone in patients with primary hyperparathyroidism
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Results of an open-label extension study reveal favorable biochemical and bone densitometric outcomes with cinacalcet therapy for up to 5.5 years in patients with mild to moderate primary hyperparathyroidism.
Researchers evaluated the long-term safety, efficacy and tolerability of cinacalcet in 45 patients with primary hyperparathyroidism. Upon completion of a double-blind, placebo-controlled, one-year trial, patients continued into a 4.5-year open-label extension study conducted at 14 study centers in the United States. All patients included in the extension were assigned to 30 mg cinacalcet twice-daily; the dose was increased to 50 mg twice-daily during a 12-week titration period if serum calcium levels were >10.3 mg/dL, and then maintained for up to 4.5 years.
Cinacalcet (Sensipar, Amgen) rapidly improved elevated serum calcium levels and maintained normocalcemia for up to 5.5 years of follow-up. After maintenance doses were established, serum calcium levels remained stable, and the proportion of patients with serum calcium <10.3 mg/dL remained stable from year two to five. Five of 41 patients required further dose adjustments during four years.
Plasma parathyroid hormone levels decreased substantially with cinacalcet, particularly by years four and five; however, levels never normalized (10 pg/mL to 65 pg/mL). Plasma parathyroid hormone was 104 pg/mL at two years, 103.4 pg/mL at three years, 88.6 pg/mL at four years and 87.7 pg/mL at five years.
“Compared with serum calcium responses, changes in plasma parathyroid hormone were slower,” the researchers wrote.
Mean serum phosphate remained within the normal range (2.6 mg/dL to 4.1 mg/dL) throughout the study, but increased during the initial 12 weeks of cinacalcet exposure. Mean serum alkaline phosphatase increased after treatment with cinacalcet during the parent study in the prior cinacalcet group and during the open-label extension in the prior placebo group. After the initial increase, serum alkaline phosphatase remained at a higher level within the normal range (35 U/L to 115 U/L).
No changes in z-scores of areal BMD at spine, hip or wrist were reported, “consistent with reports for untreated postmenopausal women or primary hyperparathyroidism patients,” according to the researchers.
Cinacalcet therapy was well tolerated. More than 98% experienced at least one mild to moderate adverse event, most commonly arthralgia (38%), myalgia (27%), diarrhea (22%), respiratory infection (20%) and nausea (20%).
The researchers concluded, “Cinacalcet is useful in the management of primary hyperparathyroidism in patients in whom parathyroidectomy is contraindicated or who have failed surgical correction of their primary hyperparathyroidism.”
Peacock M. J Clin Endocrinol Metab. 2009;94:4860-4867.
This study shows that long-term treatment of primary hyperparathyroidism maintains the improvement in serum calcium but does not improve BMD. Our group showed that similar improvement in metabolic parameters occurs in a clinical practice setting with normalization of ionized serum calcium in 81% of patients with primary hyperparathyroidism treated with cinacalcet (Sajid Crockett S. Metabolism. 2008;57:517-521). Occasional patients with severe primary hyperparathyroidism are resistant to cinacalcet. Several studies have shown that alendronate causes significant improvement in BMD in patients with primary hyperparathyroidism. Therefore, a bisphosphonate can be added to cinacalcet for long-term therapy of patients with primary hyperparathyroidism who meet the criteria for surgical therapy but are otherwise poor candidates for surgery.
- Jerome M. Hershman, MD
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