Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism

被引:3
作者
Watts, Nelson B. [1 ,17 ]
Bilezikian, John P. [2 ]
Bone, Henry G. [3 ]
Clarke, Bart L. [4 ]
Denham, Douglas [5 ]
Levine, Michael A. [6 ,7 ]
Mannstadt, Michael [8 ,9 ]
Peacock, Munro [10 ]
Rothman, Jeffrey G. [11 ]
Vokes, Tamara J. [12 ]
Warren, Mark L. [13 ]
Yin, Shaoming [14 ]
Sherry, Nicole
Shoback, Dolores M. [15 ,16 ]
机构
[1] Osteoporosis & Bone Hlth Serv, Mercy Hlth, Cincinnati, OH 45236 USA
[2] Columbia Univ, Vagelos Coll Phys & Surg, Div Endocrinol, New York, NY 10032 USA
[3] Michigan Bone & Mineral Clin, Detroit, MI 48236 USA
[4] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA
[5] Clin Trials Texas Inc, San Antonio, TX 78229 USA
[6] Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
[7] Childrens Hosp Philadelphia, Ctr Bone Hlth, Philadelphia, PA 19104 USA
[8] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA
[9] Harvard Med Sch, Boston, MA 02114 USA
[10] Indiana Univ, Dept Med, Div Endocrinol, Sch Med, Indianapolis, IN 46202 USA
[11] UPG Endocrine, Res Div, Staten Isl, NY 10301 USA
[12] Univ Chicago Med, Sect Endocrinol, Chicago, IL 60637 USA
[13] Endocrinol & Metab, Phys East, Greenville, NC 27834 USA
[14] Takeda Pharmaceut USA Inc, Lexington, MA 02421 USA
[15] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94121 USA
[16] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[17] Mercy Hlth Osteoporosis & Bone Hlth Serv, 4760 East Galbraith Rd,Suite 212, Cincinnati, OH 45236 USA
关键词
recombinant human parathyroid hormone (1-84); hypoparathyroidism; active vitamin D; calcium; bone turnover; mineral homeostasis; CONVENTIONAL TREATMENT; REPLACEMENT THERAPY; FOLLOW-UP; VITAMIN-D; PTH(1-84); MANAGEMENT;
D O I
10.1210/jendso/bvad043
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled. Objective To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment. Methods This was an open-label extension study at 12 US centers. Adults (n = 49) with chronic hypoparathyroidism were included. The intervention was rhPTH(1-84) for 6 years. The main outcome measures were safety, biochemical measures, oral supplement doses, bone indices. Results Thirty-eight patients (77.6%) completed the study. Throughout 72 months, mean albumin-adjusted serum calcium was within 2.00 to 2.25 mmol/L (8.0-9.0 mg/dL). At baseline, 65% of patients with measurements (n = 24/37) were hypercalciuric; of these, 54% (n = 13/24) were normocalciuric at month 72. Mean serum phosphorus declined from 1.6 +/- 0.19 mmol/L at baseline (n = 49) to 1.3 +/- 0.20 mmol/L at month 72 (n = 36). Mean estimated glomerular filtration rate was stable. rhPTH(1-84)-related adverse events were reported in 51.0% of patients (n = 25/49); all but 1 event were mild/moderate in severity. Mean oral calcium supplementation reduced by 45% +/- 113.6% and calcitriol by 74% +/- 39.3%. Bone turnover markers declined by month 32 to a plateau above pretreatment values; only aminoterminal propeptide of type 1 collagen remained outside the reference range. Mean bone mineral density z score fell at one-third radius and was stable at other sites. Conclusion 6 years of rhPTH(1-84) treatment was associated with sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements. rhPTH(1-84) was well tolerated; no new safety signals were identified.
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页数:16
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