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.