Endocrine Abstracts

In Europe, rhPTH(1-84) is an approved adjunctive treatment for adults with chronic hypoparathyroidism that cannot be adequately controlled with conventional therapy. Here we present data from the longest rhPTH(1-84)-treated study cohort of patients with hypoparathyroidism. In a single-centre, single-arm, phase 4 study (NCT02910466), long-term rhPTH(1-84) treatment (25, 50, 75, or 100 μg/day subcutaneously) was evaluated in adults with chronic hypoparathyroidism who maintained uninterrupted rhPTH(1-84) treatment from the HEXT study (NCT01199614). Doses were adjusted based on albumin-corrected serum calcium and 24-hour urinary calcium excretion to achieve target serum calcium within 2.00–2.25 mmol/l. Baseline was defined as last available value before first dose in the current study. End of treatment (EOT) was the day after last rhPTH(1-84) dose for each patient, including those who did not complete the study. Data are summarized as mean±SD. Thirty-nine patients enrolled (age, 51.9±12.22 years; 79.5% female; duration of hypoparathyroidism, 18.6±12.00 years). Mean length of exposure from first rhPTH(1-84) dose was 10.8±3.50 years. In the current study, 36 patients received ≥1 rhPTH(1-84) dose, and mean duration of participation was 30.3±5.79 months. Mean albumin-corrected serum calcium was 1.94±0.222 mmol/l at baseline (n=33), 2.08±0.304 mmol/l at month 30 (n=23), and 2.07±0.266 mmol/l at EOT (n=36). Phosphate values were 1.25±0.230 mmol/l at baseline (n=33), 1.30±0.241 mmol/l at month 30 (n=23), and 1.31±0.220 mmol/l at EOT (n=36). Calcium-phosphate product levels were 2.53±0.475 mmol²/l² at baseline (n=33), 2.78±0.421 mmol²/l² at month 30 (n=23), and 2.82±0.373 mmol²/l² at EOT (n=36). Mean 24-hour urinary calcium levels were 5.52±3.243 mmol/24 hours at baseline (n=35), 7.47±5.170 mmol/24 hours at month 30 (n=18), and 6.60±3.818 mmol/24 hours at EOT (n=35). Mean prescribed supplemental calcium and active vitamin D decreased from 1313.8±1404.46 mg/day and 0.17±0.320 μg/day, respectively, at baseline (n=36) to 1180.9±1065.50 mg/day and 0.12±0.327 μg/day at month 30 (n=23), and 1076.0±832.48 mg/day and 0.11±0.313 μg/day at EOT (n=36). No clinically relevant changes in bone mineral density occurred between baseline and EOT. Treatment-emergent adverse events (TEAEs) were reported in 36 (92.3%) patients; the most common were anxiety (41.0%), hypocalcaemia (28.2%), and depression (20.5%). Four TEAEs were considered by study investigators to be treatment related (upper limb fracture, hypercalcaemia, renal disorder, ureterolithiasis). Study limitations are small sample size, single-arm design, and lack of pre-treatment baseline data. Among patients with chronic hypoparathyroidism previously treated with rhPTH(1-84), improvements in biochemical efficacy parameters were maintained over a mean of 30 months of additional treatment. No new or unexpected safety signals emerged.