Risk of Chronic Kidney Disease in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

Abstract

Abstract Patients (pts) with chronic hypoparathyroidism are at increased risk of renal complications. This study evaluated chronic kidney disease (CKD) outcomes over a period of up to 5 years in adult pts with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1–84), rhPTH(1–84), compared with a historical control cohort of pts who did not receive rhPTH(1–84). The cohort of pts with chronic hypoparathyroidism treated with rhPTH(1–84) was derived from the NCT00732615 (REPLACE), NCT01268098 (RELAY), NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. The control cohort of adult pts who did not receive rhPTH(1–84) or rhPTH(1–34) was selected from the US Explorys electronic medical record database (Jan 2007−Aug 2019), using criteria similar to the enrollment criteria used in the trials. Index date was the day after treatment initiation for the rhPTH(1–84) cohort, and the day after the first calcitriol prescription for the control cohort. Pts with CKD at baseline (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 at the closest eGFR measurement before the index date) were excluded. All included pts had ≥1 eGFR measurement within 6 months before the index date and ≥2 eGFR measurements ≥3 months apart during the 5 years on or after the index date. The CKD outcome was defined as first occurrence of eGFR <60 mL/min/1.73 m2 confirmed by a second measurement ≥3 months after. Risk of CKD was assessed in a Kaplan-Meier analysis and a Cox proportional hazards model adjusted for demographic characteristics, baseline clinical conditions (including acute manifestations of hypoparathyroidism), and baseline laboratory measurements. The analysis included 118 pts in the rhPTH(1–84) cohort and 478 pts in the control cohort. Pts in the rhPTH(1–84) cohort, compared with pts in the control cohort, were younger (mean ± SD age, 45.3±11.4 vs 51.5±16.2 years; P<0.001), a higher proportion were White (97.5% vs 81.6%; P<0.001), and a lower proportion had acute manifestations of hypoparathyroidism before the index date (15.3% vs 73.2%; P<0.001). In a Kaplan-Meier analysis, rhPTH(1–84)-treated pts had a significantly reduced risk of developing CKD compared with pts in the control cohort, with 11.0% and 27.0% of pts in each cohort, respectively, developing CKD during follow-up (P<0.01). The adjusted hazard ratio of developing CKD associated with rhPTH(1–84) treatment vs no rhPTH(1–84) treatment was 0.47 (95% CI, 0.25−0.88; P<0.05). Pts with chronic hypoparathyroidism treated with rhPTH(1–84) in long-term clinical trials had a significantly reduced risk of developing CKD compared with pts in a control cohort who did not receive rhPTH(1–84). These results should be viewed in light of possible treatment differences in the studied cohorts (ie, predefined trial protocols vs real-word practice for the control cohort).