An Open-Label Extension Study of Parathyroid Hormone Rhpth(1-84) in Adults with Hypoparathyroidism

Lakatos, Péter; Bajnok, László; Lagast, Hjalmar; Valkusz, Zsuzsanna

doi:10.4158/ep15936.or

Cited by 32 publications

(53 citation statements)

References 10 publications

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“…Similar trends in the pattern of BTMs have been reported in the HEXT study (16, 18) but with differences in the magnitude of increase and time course of change that may be due to differing treatment regimens. The findings from these studies suggest the initial large increase in BTMs with rhPTH(1-84) treatment is temporary (18, 25) and is followed by a new steady state of more normal bone turnover with continued therapy. Changes in calcium and phosphorus flux from bone may at least partially explain the trend for increases in calcium supplements later in the treatment period, but this was not tested directly in this study.…”

Section: Discussionmentioning

confidence: 87%

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

Mannstadt

Clarke

Bilezikian

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. Objective To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. Design Open-label extension study; 5-year interim analysis. Setting 12 US centers. Patients Adults (N = 49) with chronic hypoparathyroidism. Intervention(s) rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum. Main Outcome Measure(s) Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal. Results Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline. Conclusion Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.

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Section: Discussionmentioning

confidence: 87%

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

Mannstadt

Clarke

Bilezikian

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…One might hypothesize that this reflects the prescriber's reasoning that due to high levels of PTH in patients with PHP, there is a higher potential for conversion into active vitamin D. Streeten et al found less morbidity from hypocalcaemia treated with vitamin D 2 than with calcitriol (24). Combination treatment with rhPTH 1-84 allows for dose reduction of calcium and active vitamin D analogue while maintaining a stable serum calcium level (25,26,27).…”

Section: Discussionmentioning

confidence: 99%

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study

David

Moyson

Vanderschueren

et al. 2019

European Journal of Endocrinology

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Objective: Chronic hypoparathyroidism and its treatment may lead to symptoms and complications affecting quality of life. We determined complications in chronic hypoparathyroid patients. Design: Retrospective cross-sectional study of patients with chronic hypoparathyroidism treated with active vitamin D supplements in a tertiary care centre during the year 2015. Primary outcome parameters were history of kidney stones and seizures and presence of renal and cerebral calcifications on imaging. Secondary outcome parameters were current symptoms of paraesthesia/cramps, hospitalization due to hyper/hypocalcaemia and hypercalciuria. Subjects: One hundred and seventy patients were included -143 (84%) with post-surgical hypoparathyroidism (PSHP), 16 (9%) with non-surgical hypoparathyroidism (NSHP) and 11 (7%) with pseudo-hypoparathyroidism (PHP). Results: History of kidney stones and seizures was present in 15 and 9% of patients, respectively. Renal and cerebral imaging was performed in 51 and 26% of the patients, with 22 and 25% of these patients having renal and cerebral calcifications respectively. Both history of seizures and cerebral calcifications were significantly more in NSHP and PHP than in PSHP patients. No association was observed between seizures and cerebral calcifications. Cramps/paraesthesia were present in 16%, and hospitalization related to hypocalcaemia was reported in 5% of the patients. Calciuria was screened in 47% at the time of consultation, and in 76% of the patients during the past 5 years. In 36% of these patients, calciuria was increased. Conclusions: Patients with chronic hypoparathyroidism frequently develop ectopic calcifications. Non-surgical patients suffer more from seizures and cerebral calcifications than patients that developed hypoparathyroidism post surgery. There is a need for increased screening of long-term complications, according to the guidelines.

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“…This therapy was well tolerated, as replacement therapy for patients with HypoPT [55]. An extension study of REPLACE showed sustained PTH (1-84) efficacy up to 48 weeks [56].…”

Section: Management Of Permanent Postsurgical Hypoparathyroidismmentioning

confidence: 92%

Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update

Iglesias

Díez

2017

Exp Clin Endocrinol Diabetes

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Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main endocrine complications after the surgical treatment for thyroid cancer. Postsurgical HypoPT can be transient, protracted or permanent. Its frequency varies according to the underlying cervical pathology, surgical technique, and mainly the experience of the surgeon. Risk factors for HypoPT include aggressiveness of the tumor, extent of surgery, the presence of parathyroid gland in the pathologic specimen, and surgeon experience. Clinical manifestations of postsurgical HypoPT can be acute or chronic. An adequate surgical technique that minimizes trauma and preserve the vascularization of the parathyroid glands is the better procedure to reduce the risk of postoperative HypoPT. Acute hypocalcemia may be managed with intravenous or oral calcium supplements, according to the level of serum calcium and the presence of signs and symptoms. Patients with permanent HypoPT require lifelong calcium and vitamin D supplementation. Calcitriol is the vitamin D metabolite of preference because of its high activity and short half-life. Both PTH (1-34) and intact PTH (1-84) have demonstrated to be attractive options in hypoparathyroid patients who cannot maintain stable serum and urinary calcium levels with calcium and vitamin D supplementation. However, the long-term safety of these preparations has not been established. Postsurgical HypoT is an unavoidable consequence of total or near-total thyroidectomy for thyroid cancer. Replacement and suppressive therapy are necessary in these patients. Thyroid hormone suppression therapy has shown to be accompanied by a decreased risk of disease progression and recurrence; however, it may also be associated with increased risk of dysrhythmia and loss of bone mass. Therefore, the intensity of TSH suppression must be established in a personalized way after balancing risk and benefits, according to the severity of the thyroid cancer, the response to therapy, and the individual risk factors for adverse events.

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An Open-Label Extension Study of Parathyroid Hormone Rhpth(1-84) in Adults with Hypoparathyroidism

Cited by 32 publications

References 10 publications

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study

Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update

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