Risk of chronic kidney disease in adult patients with chronic hypoparathyroidism treated with rhPTH(1–84) compared with a historical control cohort

2021 ◽  
Author(s):  
Elvira Gosmanova ◽  
Olulade Ayodele ◽  
Nicole Sherry ◽  
Fan Mu ◽  
Allison Briggs ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Historical Control ◽  
Adult Patients ◽  
Control Cohort ◽  
Chronic Hypoparathyroidism

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

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A267-A267
Author(s):  
Elvira Gosmanova ◽  
Olulade Ayodele ◽  
Nicole Sherry ◽  
Fan Mu ◽  
Allie Briggs ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Kidney Disease ◽  
Index Date ◽  
Historical Control ◽  
Control Cohort ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Chronic Hypoparathyroidism ◽  
Reduced Risk

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).

scholarly journals Cardiovascular Events in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A257-A257
Author(s):  
Sanjiv Kaul ◽  
Olulade Ayodele ◽  
Nicole Sherry ◽  
Elyse Swallow ◽  
Fan Mu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Index Date ◽  
Historical Control ◽  
Adult Patients ◽  
Control Cohort ◽  
Baseline Serum ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Chronic Hypoparathyroidism ◽  
Reduced Risk

Abstract Chronic hypoparathyroidism is associated with an increased risk of cardiovascular (CV) complications. This study investigated CV events over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1–84), rhPTH(1–84), compared with a historical control cohort of patients who did not receive rhPTH(1–84). The rhPTH(1–84)-treated patient cohort was derived from the NCT00732615 (REPLACE), NCT01268098 (RELAY), and NCT01297309 (RACE) clinical trials. A control cohort of adult patients 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 selection criteria similar to the enrollment criteria used in the trials. Index date was the day after initiation of treatment for the rhPTH(1–84) cohort and the day after the first calcitriol prescription for the control cohort. The primary outcome was the risk of a composite CV event (defined as any event of cerebrovascular disease, coronary artery disease, heart failure, or peripheral vascular disease) in the rhPTH(1–84) cohort compared with the control cohort through 5 years post-index. Patients with a CV event at baseline were excluded from the analysis. Risk of a CV event was assessed in a Kaplan-Meier analysis and a Cox proportional hazards model adjusted for demographic characteristics, baseline clinical conditions, and baseline serum calcium levels. The analysis included 113 patients in the rhPTH(1–84) cohort and 618 patients in the control cohort. Patients in the rhPTH(1–84) cohort, compared with the control cohort, were younger (mean ± SD age, 47.8±12.0 vs 51.0±16.8 years; P<0.05), a higher proportion were White (94.7% vs 81.9%; P<0.01), and fewer had acute manifestations of hypoparathyroidism before the index date (22.1% vs 69.6%; P<0.001). In a Kaplan-Meier analysis, rhPTH(1–84)-treated patients had a significantly reduced risk of developing a CV event compared with patients in the control cohort (P<0.01); 3.5% of rhPTH(1–84)-treated patients and 16.3% of control cohort patients developed a CV event over the 5-year follow-up period. The adjusted hazard ratio for developing a CV event associated with rhPTH(1–84) treatment vs no rhPTH(1–84) treatment was 0.23 (95% CI, 0.07−0.74; P<0.05). This analysis is limited by differences in patient management under predefined clinical trial protocols for the rhPTH(1–84) cohort vs real-world clinical practice for the control cohort. Over 5 years, patients with chronic hypoparathyroidism treated with rhPTH(1–84) in clinical trials had a significantly reduced risk of CV events compared with a control cohort of patients who did not receive rhPTH(1–84). Further research is needed to better understand the mechanism underlying the association between chronic hypoparathyroidism and risk of developing a CV event.

scholarly journals Serum Calcium Levels in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A268-A268
Author(s):  
Lars Rejnmark ◽  
Olulade Ayodele ◽  
Nicole Sherry ◽  
Fan Mu ◽  
Angela Lax ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Index Date ◽  
Data Interpretation ◽  
Lower Proportion ◽  
Historical Control ◽  
Adult Patients ◽  
Target Range ◽  
Similar Proportion ◽  
Control Cohort ◽  
Chronic Hypoparathyroidism

Abstract Adult patients (pts) with chronic hypoparathyroidism (HypoPT) have wide fluctuations in albumin-corrected serum calcium (Ca) measurements.1 This study assessed Ca levels over a 5-yr period in adult pts with chronic HypoPT treated with or without recombinant human parathyroid hormone (1–84), rhPTH(1–84). The rhPTH(1–84)-treated pt cohort was from NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. A historical control pt cohort with chronic HypoPT who did not receive rhPTH(1–84) or rhPTH(1–34) came from the US Explorys electronic medical record database (Jan 2007−Aug 2019); selection criteria were similar to those used for the rhPTH(1–84)-treated cohort. The index date was the day after initiation of treatment for the rhPTH(1–84) cohort and the day after the first calcitriol prescription for the control cohort. Pts were required to have ≥1 pair of serum albumin and Ca values occurring on the same date during the 6 months before index and 5 yrs (±6 months) after index. For pts from RACE, baseline and study visit data after rhPTH(1–84) initiation were collected from the antecedent trials. Specified ranges for albumin-corrected serum Ca values were: <7.5 mg/dL (<1.875 mmol/L); ≥7.5−<8.0 mg/dL (≥1.875−<2.0 mmol/L); ≥8.0−<9.0 mg/dL (≥2.0−<2.25 mmol/L); ≥9.0−<10.2 mg/dL (≥2.25−<2.55 mmol/L); and ≥10.2 mg/dL (≥2.55 mmol/L). Changes in Ca levels were assessed using multivariable regression models. There were 71 pts in the rhPTH(1–84) cohort and 119 pts in the control. Before the index date, rhPTH(1–84)-treated pts, compared with the control, were younger (mean±SD, 47.8±10.8 vs 54.9±15.5 years; P<0.001) and a lower proportion had acute manifestations of HypoPT (22.5% vs 64.7%; P<0.001). Over a 5-yr period, in adjusted analyses rhPTH(1–84)-treated pts, compared with the control, had a similar mean proportion of <7.5 mg/dL Ca measurements per pt (13.1% vs 13.1%; P=0.41), a higher proportion of ≥7.5−<8.0 mg/dL Ca measurements per pt (18.8% vs 10.6%; P<0.001), a similar proportion of ≥8.0−<9.0 mg/dL Ca measurements per pt (50.7% vs 48.5%; P=0.68), a lower proportion of ≥9.0−<10.2 mg/dL Ca measurements per pt (15.6% vs 24.1%; P<0.001), and a lower proportion of ≥10.2 mg/dL Ca measurements per pt (1.9% vs 3.7%; P=0.27). The rhPTH(1–84) cohort, compared with the control, had a higher proportion of pts with target range Ca measurements ≥7.5−<9.0 mg/dL (≥1.875−<2.25 mmol/L) for at least 50% of their values (88.7% vs 62.2%; P<0.001). Data interpretation is limited by the differing pt management (ie, trial protocols for the rhPTH[1–84] cohort and clinical practice for the control cohort). Over a 5-yr period, per pt serum Ca levels fluctuated in pts with chronic HypoPT, but levels were more stable in pts treated with rhPTH(1–84) and a lower proportion had hypercalcemia, compared with controls. 1. Ayodele O, et al. ASBMR 2020, 11−15 Sep 2020.

scholarly journals Change in Estimated Glomerular Filtration Rate in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A257-A258
Author(s):  
Olulade Ayodele ◽  
Lars Rejnmark ◽  
Nicole Sherry ◽  
Elyse Swallow ◽  
Allie Briggs ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Index Date ◽  
Estimated Glomerular Filtration Rate ◽  
Data Interpretation ◽  
Historical Control ◽  
Adult Patients ◽  
Control Cohort ◽  
Chronic Hypoparathyroidism

Abstract Chronic hypoparathyroidism (HypoPT) is associated with impaired renal function.1 This study evaluated change in estimated glomerular filtration rate (eGFR) over a 5-yr period in adult patients (pts) with chronic HypoPT treated with or without recombinant human parathyroid hormone (1–84), rhPTH(1–84). The rhPTH(1–84)-treated pt cohort was derived from NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. A historical control pt cohort with HypoPT who did not receive rhPTH(1–84) or rhPTH(1–34) were from the large national US Explorys electronic medical record database (Jan 2007−Aug 2019) using criteria similar to the trial enrollment criteria. The 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. The analysis included pts with eGFR ≥60 mL/min/1.73 m2 at the closest eGFR measurement during the 6 months before index date, ≥2 eGFR measurements ≥3 months apart during the 5 yrs on or after the index date and ≥1 eGFR measurement at 5 yrs (±6 months). For pts from RACE, baseline and study visit data after rhPTH(1–84) initiation were collected from the antecedent trials. Changes in eGFR were assessed in linear mixed and multivariable models (adjusted for age/sex/race, baseline eGFR value, history of hypercalciuria/hypertension/type 2 diabetes (T2D)/acute HypoPT manifestations/cardiovascular condition). There were 72 pts in the rhPTH(1–84) cohort and 174 in the control cohort. Before the index date, pts in the rhPTH(1–84) cohort, compared with the control, were younger (mean±SD, 47.5±11.0 vs 53.9±15.5 yrs; P<0.01), and a lower proportion had acute manifestations of HypoPT (22.2% vs 69.0%; P<0.001) and T2D (2.8% vs 17.8%; P<0.001). Over the 5-yr period, the difference in the rate of eGFR change between the 2 cohorts was 1.45 mL/min/1.73 m2 per yr and 1.33 mL/min/1.73m2 per yr, in the unadjusted and adjusted linear mixed models respectively (both P<0.001); eGFR remained higher in the rhPTH(1–84) cohort at all times. Over 5 yrs, eGFR was relatively stable in the rhPTH(1–84) cohort, but eGFR declined in the control at a rate of −1.58 mL/min/1.73 m2 per yr (unadjusted model, P<0.001), and by −1.57 mL/min/1.73 m2 per yr (adjusted model, P<0.001). By yr 5, pts in the rhPTH(1–84) and control cohort were predicted to have eGFR changes from baseline of +1.51 mL/min/1.73 m2 and −10.48 mL/min/1.73 m2, respectively. Data interpretation is limited by the differing pt management (ie, predefined trial protocols and clinical practice for the control). In pts with chronic HypoPT, the annual rate of eGFR decline over a 5-yr period was significantly lower in pts treated with rhPTH(1–84) compared with controls not treated with rhPTH(1–84). These results support the Chen et al1 analysis of data from the same trials and a regional US health record database. 1. Chen KS, et al. JCEM 2020;105(10)dgaa490

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