Hypoparathyroidism is a disorder of mineral homoeostasis due to parathyroid hormone (PTH) deficiency. Conventional treatment with oral Ca and calcitriol may maintain serum Ca levels but does not replace other physiologic PTH effects. RACE is an ongoing open-label study of recombinant human PTH1-84 (rhPTH1-84) for hypoparathyroidism treatment in adults (ClinicalTrials.gov NCT01297309). Patients initially received rhPTH1-84 25 or 50 μg/day subcutaneously, with 25-μg increases to 100 μg/day maximum. rhPTH(1-84) could be titrated and oral Ca/calcitriol doses adjusted at any time during the study to maintain serum Ca levels within the optimised target (2.02.2 mmol/l). Primary objective was to demonstrate the long-term safety and tolerability of rhPTH1-84. Composite efficacy endpoint was the proportion of patients who achieved a ≥50% reduction from baseline (BL) in oral Ca dose (or Ca ≤500 mg/day) and a ≥50% reduction from BL in calcitriol dose (or calcitriol ≤0.25 μg/day) while maintaining albumin-adjusted serum Ca between 1.87 mmol/l and the ULN for the central laboratory. Five-year, open-label efficacy and safety data presented with descriptive summary statistics (mean(S.D.)). Study cohort included 49 adult patients enrolled at 12 US centres (age 48.1[9.78] years; 81.6% female); 40 patients (81.6%) completed 60 months (M60) of rhPTH(1-84) as of 8 May 2017. Oral Ca and calcitriol doses were reduced by 53.4% and 75.7%, respectively; albumin-adjusted serum Ca levels were maintained within the target range (M60, 2.1[0.20] mmol/l; BL, 2.1[0.17] mmol/l). At M60, the efficacy composite endpoint was achieved by 28/40 patients. Urinary Ca excretion showed a numerical reduction (M60, 6.2[3.30] mmol/24 h; BL, 8.9[5.01] mmol/24 h, n=48), as did serum P levels (M60, 1.3[0.21] mmol/l; BL, 1.6[0.19] mmol/l,) and Ca-P product levels (M60, 2.8[0.45] mmol2/l2; BL, 3.4[0.51] mmol2/l2). Serum creatinine levels remained stable (M60, 81.7[19.85] μmol/l; BL, 84.7±18.16 μmol/l), as did estimated glomerular filtration rate (M60, 108.1[42.32] ml/min; BL, 108.2[36.36] ml/min, n=41). Treatment-emergent adverse events (TEAEs) were reported in 48/49 patients. Common TEAEs (>25% of patients) reported included symptoms of the underlying disease (ie, hypocalcaemia [36.7%], muscle spasms [32.7%], paraesthesia [30.6%]), sinusitis (30.6%), and nausea (30.6%). Serious TEAEs occurred in 13 patients. Continuous use of rhPTH1-84 over 5 years has an acceptable safety profile, was well tolerated, efficacious, and improved key measurements of mineral homoeostasis.
19 - 22 May 2018
European Society of Endocrinology