ECTS Abstracts (2015) 1 P82

Long-term effects of recombinant human parathyroid hormone, rhPTH(1-84), on bone remodelling in patients with hypoparathyroidism: 3-year data from the open-label RACE study

Michael A Levine1, John P Bilezikian2, Bart L Clarke3, Michael Mannstadt4, Tamara J Vokes5, Mark L Warren6, Hjalmar Lagast7 & Dolores M Shoback8

1Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 2College of Physicians and Surgeons, Columbia University, New York, NY, USA; 3Mayo Clinic Division of Endocrinology, Diabetes, Metabolism, & Nutrition, Rochester, MN, USA; 4Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 5University of Chicago Medicine, Chicago, IL, USA; 6Endocrinology and Metabolism, Physicians East, PA, Greenville, NC, USA; 7NPS Pharmaceuticals, Inc., Bedminster, NJ, USA; 8SF Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, USA.

Deficient parathyroid hormone, the hallmark of hypoparathyroidism, can lead to low bone turnover and increased bone mineral density (BMD). In the pivotal phase III, placebo-controlled REPLACE study and the subsequent dose-blinded RELAY study, treatment with rhPTH(1-84) restored mineral homeostasis and increased bone turnover markers (BTMs) in patients with hypoparathyroidism. In RACE, an open-label extension trial of REPLACE and RELAY, patients initiated treatment with subcutaneous rhPTH(1-84) at 25 or 50 μg/day, with possible up-titration to 50, 75, or 100 μg/day if active vitamin D and oral calcium could be further reduced. Serial measurements of serum calcium and phosphorus were performed, and serum BTMs were analysed, including BSAP, CTX, and P1NP. BMD was measured annually by dual-energy X-ray absorptiometry. All data presented as mean ± SD. This analysis included 39 patients (79% female) who received at least 36 months of rhPTH(1-84) therapy. Hypoparathyroidism duration was 16±13 years. At baseline, optimised albumin-corrected serum calcium and phosphorus levels were 2.1±0.2 and 1.6±0.2 mmol/L, respectively. At month 36, serum calcium was maintained at 2.1±0.2 mmol/L, whereas serum phosphorus decreased to 1.4±0.2 mmol/L. Baseline BTMs were low-normal (BSAP, 9.3±3.2 μg/L; CTX, 206.9±171.3 ng/L; P1NP, 32.3±18.3 μg/L). Actual BTM levels increased at month 36 (BSAP, 15.6±9.4 μg/L; CTX, 480.3±457.1 ng/L; P1NP, 129.7±114.7 μg/L). A trend toward BMD Z-score reduction was observed at all sites except lumbar spine (change from baseline at month 36: total hip, −0.05±0.51; femoral neck, −0.05±0.61; distal one-third radius, −0.44±0.76; lumbar spine, 0.24±0.84). Adverse events were similar to those in the REPLACE study. Long-term treatment of patients with rhPTH(1-84) was associated with continued improvement in bone and mineral homeostasis, evidenced by increases in BTMs, reductions in most BMD Z-scores, and improved serum calcium and phosphorus levels. The results provide further evidence for the clinical utility and efficacy of rhPTH(1-84) in the treatment of hypoparathyroidism.

Disclosure: This work was supported by NPS Pharmaceuticals, Inc., Bedminster, NJ, USA.