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

Nelson B Watts; John P Bilezikian; Henry G Bone; Bart L Clarke; Douglas Denham; Michael A Levine; Michael Mannstadt; Munro Peacock; Jeffrey G Rothman; Tamara J Vokes; Mark L Warren; Shaoming Yin; Nicole Sherry; Dolores M Shoback

doi:10.1210/jendso/bvad043

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

J Endocr Soc. 2023 Apr 4;7(5):bvad043. doi: 10.1210/jendso/bvad043. eCollection 2023 Mar 6.

Authors

Affiliations

¹ Osteoporosis and Bone Health Services, Mercy Health, Cincinnati, OH 45236, USA.
² Division of Endocrinology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
³ Michigan Bone and Mineral Clinic, PC, Detroit, MI 48236, USA.
⁴ Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN 55905, USA.
⁵ Clinical Trials of Texas, Inc., San Antonio, TX 78229, USA.
⁶ Division of Endocrinology and Diabetes and Center for Bone Health, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁷ Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁸ Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁹ UPG-Endocrine (Research Division), Staten Island, NY 10301, USA.
¹⁰ Section of Endocrinology, University of Chicago Medicine, Chicago, IL 60637, USA.
¹¹ Endocrinology and Metabolism, Physicians East, PA, Greenville, NC 27834, USA.
¹² Takeda Pharmaceuticals USA, Inc., Lexington, MA 02421, USA.
¹³ Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
¹⁴ Department of Medicine, University of California, San Francisco, CA 94143, USA.

Abstract

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.

Keywords: active vitamin D; bone turnover; calcium; hypoparathyroidism; mineral homeostasis; recombinant human parathyroid hormone (1-84).

Grants and funding

R01 DK079970/DK/NIDDK NIH HHS/United States