Real-world data for effectiveness and safety of palopegteriparatide in patients with chronic hypoparathyroidism: the...

Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, requiring lifelong treatment with activated vitamin-D and oral calcium supplements. Palopegteriparatide, a novel long-acting prodrug of PTH (1-34), has demonstrated efficacy in randomized controlled trials, but real-world data on its long-term effectiveness and safety remain limited.

To evaluate the efficacy and safety of long-term palopegteriparatide therapy in a real-world cohort of patients with HypoPT.

Multicenter prospective cohort study conducted in tertiary referral hospitals. The study is registered at ClinicalTrials.gov under the identifier NCT07299838.

Ninety-two adults with HypoPT (79 females, 13 males), previously treated with recombinant human PTH (1-84) or conventional therapy, initiated palopegteriparatide according to the National Hellenic Guidelines for the management of HypoPT.

Patients were treated for a median duration of 6.5 months (range 2-14), with significant improvements in biochemical control of calcium-phosphate metabolism. Albumin-adjusted calcium increased from 8.14 ± 0.73 to 8.99 ± 0.94 mg/dL, and magnesium from 1.79 ± 0.17 to 1.96 ± 0.17 mg/dL (both P < .001). Phosphate decreased from 4.74 ± 0.97 to 4.02 ± 0.63 mg/dL (P < .001), Ca × P product from 38.27 ± 6.92 to 36.04 ± 6.55 mg2/dL2 (P = .017), and 24-hour urinary calcium from 245.7 ± 125.5 to 164.5 ± 88.3 mg/24 h (P < .001). Daily pill burden was markedly reduced, and 58% of patients achieved independence from calcium supplements and alfacalcidol after a median of 30 days. Adverse events were mostly mild and transient.

In a real-world setting, palopegteriparatide effectively normalizes calcium-phosphate homeostasis, reduces hypercalciuria, and substantially decreases reliance on conventional therapy, with a favorable safety profile.