ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2018) 56 OC3.4 | DOI: 10.1530/endoabs.56.OC3.4

Renal function change in chronic hypoparathyroidism patients treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) and in a historical control cohort treated with standard therapy

Kristina Chen1, Mishaela Rubin2, Fan Mu3, Elyse Swallow3, Jing Zhao3, Jessie Wang3, Alan Krasner1, Nicole Sherry1, James Signorovitch3, Markus Ketteler4 & John Bilezikian2

1Shire Human Genetic Therapies, Inc., Lexington, Kentucky, USA; 2Columbia University College of Physicians and Surgeons, New York, New York, USA; 3Analysis Group Inc., Boston, Massachusetts, USA; 4Division of Nephrology, Klinikum Coburg, Coburg, Germany.

Standard therapy (ST) for chronic hypoparathyroidism (HPT) includes calcium and active vitamin D supplementation, which can be associated with an increased risk of renal complications. This study compared renal function change, assessed by estimated glomerular filtration rate (eGFR) over 5 years between HPT patients receiving rhPTH1-84 as an adjunct to ST and a historical control cohort without rhPTH1-84. rhPTH1-84-treated HPT patients were selected from two single-arm, long-term, open-label studies, RACE (NCT01297309) and NCT02910466. Historical control patients were selected from the MedMining database using similar inclusion criteria to the two studies. Patients were required to have ≥2 eGFR measures, 5 years apart, after HPT diagnosis. Index date was defined as the baseline visit in the rhPTH1-84-treated cohort and as the 1st eligible eGFR measure date in the historical control cohort. eGFR change over time was compared using a multivariable model, adjusting for age, sex, history of hypertension, cardiac disorders, diabetes mellitus, hypercalcemia, hypocalcemia, concomitant nephrotoxic drug use, and baseline eGFR. A sensitivity analysis was conducted with a 3-year follow-up, which included patients with ≥2 eGFR measures, 3 years apart, after HPT diagnosis. One hundred and twenty two patients (N=69 with and 53 without rhPTH1-84) were included in the 5-year analyses. At baseline, rhPTH1-84-treated patients were nominally younger (51.7 vs 55.8 years) and had lower eGFR (75.5 vs 82.5 ml/min per 1.73 mm2). Race and sex were similar between cohorts. A lower proportion of rhPTH1-84-treated patients had concomitant nephrotoxic drug use or a history of hypocalcemia, hypercalcemia, hypertension, diabetes mellitus, or cardiac disorders. Characteristics were similar in the 3-year sensitivity cohorts (N=75 with and 76 without rhPTH1-84). In the adjusted model, predicted eGFR change at year 5 was +5.80 vs −5.56 ml/min per 1.73 mm2 in the rhPTH-treated vs historical control cohort. Annual rate of eGFR decline over 5 years of follow-up was significantly lower in rhPTH1-84-treated patients (difference in annual eGFR change=2.13 ml/min per 1.73 mm2; P=0.002). The trend in eGFR change over 3 years was similar in the sensitivity analysis (difference in annual eGFR change=2.96 ml/min per 1.73 mm2; P<0.001). In this non-randomized post-hoc analysis, patients with chronic HPT without rhPTH1-84 treatment exhibited significantly greater decline in eGFR than patients receiving rhPTH1-84 over 5 years, with and without adjusting for confounders. This difference was also observed over 3 years in similar cohorts. This analysis is hypothesis generating and further research is warranted.