Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism


Mannstadt M, Clarke BL, Bilezikian JP, Bone H, Denham D, Levine MA, Peacock M, Rothman J, Shoback DM, Warren ML, et al. Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism. Journal of Clinical Endocrinology & Metabolism [Internet]. 2019;104 (11) :5136–5147.


Context: Conventional treatment of hypoparathyroidism with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by deficiency of parathyroid hormone (PTH).

Objective: To evaluate long-term safety and tolerability of recombinant human PTH(1-84) (rhPTH[1-84])

Design: Open-label extension study; 5-year interim analysis

Setting: 12 US centers

Patients: Adults (N=49) with chronic hypoparathyroidism

Intervention(s): Patients initially received rhPTH(1-84) 25 or 50 µg/day, with 25-µg adjustments permitted to 100 µg/day maximum.

Main Outcome Measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/day) and calcitriol (or ≤0.25 µg/day) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal.

Results: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium remained between 8.2 and 8.7 mg/dL. Between baseline and Month 60, urinary calcium decreased by 101.2±236.24 mg/24 hours, serum phosphorus decreased by 1.0±0.78 mg/dL, and calcium-phosphorus product decreased by 8.5±8.29 mg2/dL2. Serum creatinine and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At Month 60, 28/40 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at approximately 12 months, and then declined to values that remained above baseline.

Conclusions: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.

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Last updated on 03/03/2020