Long-Term rhPTH(1-84) Associated With Reduced Need for Calcium, Calcitriol Supplements

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Long-term treatment with recombinant human parathyroid hormone may reduce need for calcium and calcitriol supplements.
Long-term treatment with recombinant human parathyroid hormone may reduce need for calcium and calcitriol supplements.

Continuous treatment rhPTH(1-84) appeared to reduce the need for supplemental calcium and calcitriol requirements and reduced urinary calcium excretion in 33 patients with hypoparathyroidism.

rhPTH(1–84), a recombinant human parathyroid hormone, was also associated with stable serum calcium concentration.

“Administration of rhPTH(1–84) led to sustained improvements in calcium metabolism, with progressive reductions in supplemental calcium and 1,25-dihydroxyvitamin D requirements and in urinary calcium excretion,” researchers wrote in the Journal of Clinical Endocrinology & Metabolism. “This study has demonstrated that rhPTH(1–84) is safe and effective as a long-term treatment of hypoparathyroidism for at least 6 years. It permits major reductions in the need for supplemental calcium and active vitamin D while maintaining normal calcium levels.”

Thirty-three patients, 79% women, with hypoparathyroidism were initially assigned to 100 μg subcutaneous rhPTH(1–84) every other day. Dosing was titrated over the course of the study to avoid hyper- and hypocalcemic symptoms and maintain serum calcium ≤8.5 mg/dL and >7.5 mg/dL with calcium supplementation of ≤1.5 g daily and calcitriol dose of ≤0.25 g daily. The most common dose during the final 2 years was 50 μg daily, and 90% of patients were on daily dosing by the study's conclusion.

Supplemental calcium requirements declined significantly within 1 year of initiation with rhPTH(1–84) (P<.0001) and remained lower than baseline throughout the study period. At 6 years, the average reduction in calcium supplementation at study conclusion was 53%. Only 9 patients required more than 1.5 g per day of calcium supplementation at 6 years compared with 25 at baseline.

1,25-dihydroxyvitamin D requirements also fell significantly

within the first year of treatment (P=.001), and continued falling through year 6 (P=.02 vs year 1). By study's end, 1,25-dihydroxyvitamin D requirements had fallen by 67%. Almost half the cohort (48%)  eliminated supplementation altogether.

Serum calcium levels remained in the lower range of normal throughout the study (8.6 mg/dL to 8.4 mg/dL; P=.53). Urinary calcium excretion fell significantly below pretreatment levels at year 1, year 3, and year 6 (baseline, 275 mg per day; year 6, 186 mg per day, P=.007).

Researchers observed 12 hypercalcemic events (serum calcium, 10.2 mg/dL) in 9 patients during the study (2.5% of all values). None of the patients who experienced hypercalcemia required hospitalization.

The most common adverse events were musculoskeletal complaints. Researchers said many adverse events — including nausea, headache, fatiue, and dizziness — declined in severity after the first year.

Reference

  1. Rubin MR, Cusano NE, Fan W, et al. Therapy of Hypoparathyroidism with PTH(1–84): a Prospective Six Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab. 2016. doi: 10.1210/jc.2015-4135.
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