The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1‐84): A retrospective cohort study

Rejnmark, Lars; Ayodele, Olulade; Lax, Angela; Mu, Fan; Swallow, Elyse; Gosmanova, Elvira O.

doi:10.1111/cen.14813

Cited by 7 publications

(2 citation statements)

References 24 publications

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“… 9 In a previous study, patients who received rhPTH(1–84) had a significantly lower risk of chronic kidney disease over a 5-yr period compared to a historical control cohort of patients with HypoPT who received conventional treatment. 36 …”

Section: Discussionmentioning

confidence: 99%

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism

Khan,

Abbott,

Ahmed

et al. 2024

JBMR Plus

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Hypoparathyroidism is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1–84 (rhPTH[1–84]) for treating hypoparathyroidism. The present study (NCT03364738) was a Phase 4, 1-year open-label extension of PARALLAX. Patients received only two doses of rhPTH(1–84) in PARALLAX and were thus considered treatment-naive at the start of the current study. rhPTH(1–84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 years; 81.8% were women, and 90.9% were White. By end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined primary endpoint range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-hour urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402–855 mg/day and 0.8–0.2 μg/day, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2–5 fold from baseline to EOT. HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1–84) once daily for 1 year improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.

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Section: Discussionmentioning

confidence: 99%

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism

Khan,

Abbott,

Ahmed

et al. 2024

JBMR Plus

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“…Several retrospective cohort studies of adults with chronic hypoparathyroidism treated with PTH therapy as an adjunctive treatment to conventional therapy had preservation of eGFR over 5 years, in contrast to a decline in eGFR in historical control cohorts [13][14][15]. A retrospective cohort study by Rejnmark et al showed that participants with chronic hypoparathyroidism from randomized, double-blind, placebo-controlled trials and open-label studies treated with recombinant human (rh) PTH (1-84) had a 53% lower risk of developing CKD (HR 0.5, 95% CI 0.3-0.9) and 65% lower risk for sustained eGFR decline C 30% from baseline (HR 0.4, 95% CI 0.1-0.9) compared with a historical control cohort of adults with chronic hypoparathyroidism selected from an electronic medical record database who had a prescription for active vitamin D but no use of rhPTH (1-84) or teriparatide [15]. These findings suggest that, in contrast to conventional therapy, PTH therapy may have a protective effect on renal function in individuals with hypoparathyroidism.…”

Section: Discussionmentioning

confidence: 99%

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

Rejnmark,

Gosmanova,

Khan

et al. 2024

Adv Ther

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Introduction Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. Methods PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m 2 . Results At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m 2 from baseline ( P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m 2 . In participants with baseline eGFR < 60 mL/min/1.73 m 2 , 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m 2 ( P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. Conclusion In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. Trial Registration ClinicalTrials.gov NCT04701203. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-024-02843-8.

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New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases

di Filippo,

Bilezikian,

Canalis

et al. 2024

Endocrine

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The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1‐84): A retrospective cohort study

Cited by 7 publications

References 24 publications

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases

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