Endocrine Abstracts (2017) 49 GP47 | DOI: 10.1530/endoabs.49.GP47

Recombinant human parathyroid hormone (rhPTH[1-84], parathyroid hormone rDNA) improves hypercalciuria in patients with hypoparathyroidism: 3-year analysis from RACE study

Bart L Clarke1, Tamara J Vokes2, John P Bilezikian3, Henry G Bone4, Douglas S Denham5, Hak-Myung Lee6, Michael A Levine7, Michael Mannstadt8, Munro Peacock9, Jeffrey G Rothman10, Dolores M Shoback11, Mark L Warren12, Nelson B Watts13 & Alan Krasner6

1Mayo Clinic, Rochester, Minnesota, USA; 2University of Chicago Medicine, Chicago, Illinois, USA; 3College of Physicians and Surgeons, Columbia University, New York, New York, USA; 4Michigan Bone and Mineral Clinic, PC, Detroit, Michigan, USA; 5Clinical Trials of Texas, Inc., San Antonio, Texas, USA; 6Shire Human Genetic Therapies, Inc., Lexington, Massachusetts, USA; 7Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; 8Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; 9Indiana University School of Medicine, Indianapolis, Indiana, USA; 10Staten Island University Hospital, Staten Island, New York, USA; 11Endocrine Research Unit, Department of Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, California, USA; 12Physicians East, PA, Greenville, North Carolina, USA; 13Mercy Health, Cincinnati, Ohio, USA.

Hypoparathyroidism (HPT) is characterised by hypocalcaemia and impaired renal phosphate excretion and calcium conservation. Oral calcium supplements and calcitriol can improve serum calcium levels but lack the physiologic effects of PTH on renal reabsorption of calcium. RACE is an ongoing open-label study evaluating the long-term safety of recombinant human parathyroid hormone 1-84 (rhPTH[1-84], parathyroid hormone rDNA) in adults with HPT (NCT01297309). In this interim analysis, we report the 3-year treatment effect with 25–100 μg/day rhPTH(1-84) on 24-h urinary calcium levels, with or without thiazide diuretics. All data are presented as mean (SD). The study cohort comprised 49 patients enrolled at 12 USA centres; 38 (78%) completed 36 months of rhPTH(1-84) treatment. Baseline demographics were as follows: 82% women, age 48 (9.8) years, HPT duration of 16 (12.5) years, 100% taking prescribed calcium supplements and calcitriol. In response to rhPTH(1-84), albumin-corrected serum calcium remained within the target range over the 3 years; 2.1 (0.17) mmol/l at baseline (i.e., start of rhPTH[1-84], n=49) and Month 36 (n=36). Treatment with rhPTH(1-84) also led to a reduction in urinary calcium, from baseline 8.9 (5.0) mmol/24 h to 6.5 (2.8) mmol/24 h (n=35; P<0.05). Urinary calcium excretion at Month 36 was similar for men compared with women, and in patients taking or not taking thiazide diuretics. Overall, 71% of rhPTH(1-84)−treated patients with baseline hypercalciuria had normal 24-h urinary calcium excretion at Month 36 (n=12/17). Treatment with rhPTH(1-84) improved calcium–phosphate product from baseline 3.4 (0.5) mmol2/l2 (n=49) to 2.9 (0.5) mmol2/l2 (n=36) (P<0.0001). eGFR was baseline 108.2 (36.4) ml/min (n=41) and 115.7 (47.3) ml/min (n=36) at Month 36 (P<0.0772). Over 3 years, rhPTH(1-84) maintained target levels of serum calcium and reduced urinary calcium to normal levels in HPT patients. More information is needed to understand the timing of the beneficial effect on urinary calcium excretion.