학술논문
Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. November 2019, Vol. 104 Issue 11, p5136, 12 p.
Subject
Language
English
ISSN
0021-972X
Abstract
PTH plays a central role in mineral homeostasis by stimulating renal reabsorption of calcium, promoting renal phosphate excretion, and stimulating conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (1,25[[OH].sub.2]D), the fully [...]
Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. 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): rhPTH(1-84) 25 or 50 [micro]g/d initially, with 25-mg adjustments permitted to a 100 [micro]g/d maximum. Main Outcome Measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with [greater than or equal to]50% reduction in oral calcium (or [less than or equal to]500 [micro]g/d) and calcitriol (or [less than or equal to]0.25 [micro]g/d) 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 levels remained between 8.2 and 8.7 [micro]g/dL. Between baseline and month 60, levels [+ or -] SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 [+ or -] 236.24 mg/24 hours, 1.0 [+ or -] 0.78 [micro]g/dL, and 8.5 [+ or -] 8.29 [mg.sup.2]/[dL.sup.2], respectively. Serum creatinine level 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 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ~12 months, and then declined to values that remained above baseline. Conclusion: Treatment with rhPTH(1-84) for = years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters. (J Clin Endocrinol Metab 104: 5136-5147, 2019)
Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. 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): rhPTH(1-84) 25 or 50 [micro]g/d initially, with 25-mg adjustments permitted to a 100 [micro]g/d maximum. Main Outcome Measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with [greater than or equal to]50% reduction in oral calcium (or [less than or equal to]500 [micro]g/d) and calcitriol (or [less than or equal to]0.25 [micro]g/d) 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 levels remained between 8.2 and 8.7 [micro]g/dL. Between baseline and month 60, levels [+ or -] SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 [+ or -] 236.24 mg/24 hours, 1.0 [+ or -] 0.78 [micro]g/dL, and 8.5 [+ or -] 8.29 [mg.sup.2]/[dL.sup.2], respectively. Serum creatinine level 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 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ~12 months, and then declined to values that remained above baseline. Conclusion: Treatment with rhPTH(1-84) for = years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters. (J Clin Endocrinol Metab 104: 5136-5147, 2019)