Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly

Shimatsu, Akira; Nagashima, Masahito; Hashigaki, Satoshi; Ohki, Nobuhiko; Chihara, Kazuo

doi:10.1507/endocrj.ej15-0619

Cited by 11 publications

(5 citation statements)

References 16 publications

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“…In most of the studies, the response rate in patients treated with first-generation SSAs ranges from 17% to 41% [2,[23][24][25]. In a retrospective study, pegvisomant monotherapy showed efficacy with sustained IGF-1 normalization in Japanese patients with acromegaly; however, there was no effect on GH reduction and tumor shrinkage, and safety concerns like liver toxicity were observed [26], which is consistent with the known profile of pegvisomant. Until now, no publications evaluating dopamine agonist monotherapy in Japanese population with acromegaly/pituitary gigantism are available.…”

Section: Discussionsupporting

confidence: 58%

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

et al. 2017

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ACROMEGALY AND PITUITARY GIGANTISM are rare conditions characterized by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma leading to overproduction of insulin-like growth factor-1 (IGF-1) [1]. Elevated GH and IGF-1 levels lead to metabolic dysfunction and somatic overgrowth, resulting in significant morbidity and mortality. Therefore, the recommended treatment approach is to normalize GH and IGF-1 levels [2]. Abstract.A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GH<2.5μg/L and IGF-1< lower limit of normal). Reductions in the median GH and IGF-1 levels observed at month 3 were maintained up to month 12; the median percent change from baseline to month 12 in GH and IGF-1 levels were −74.71% and −59.33%, respectively. Twenty-nine patients completed the 12-month core phase, 1 withdrew consent, and 3 discontinued treatment due to adverse events (AEs; diabetes mellitus, hyperglycemia, liver function abnormality, n=1 each). Almost all patients (97%; 32/33) experienced AEs; the most common AEs were nasopharyngitis (48.5%), hyperglycemia (42.4%), diabetes mellitus (24.2%), constipation (18.2%), and hypoglycemia (15.2%). Serious AEs were reported in 7 patients with the most common being hyperglycemia (n=2). Long-acting pasireotide demonstrated clinically relevant efficacy and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

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Section: Discussionsupporting

confidence: 58%

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

et al. 2017

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“…Kasuki et al (23) reported the experience with pegvisomant in a single Brazilian center and observed in 2 of their 27 patients (7.4%) mild (1.5 and 2.3× ULN) and transitory elevations of liver enzymes. In a report of Japanese patients with acromegaly, Shimatsu et al (24) reported ALT and AST increases in 3 (2 mild and 1 moderate) of 16 patients (16.7%), which resolved after discontinuation of pegvisomant. The results of this analysis are consistent with observations from the initial clinical trials and prior long-term observational data (3,8,10,11,12,13,14,15,22).…”

Section: Discussionmentioning

confidence: 99%

Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY

Buchfelder

Lely

Biller

et al. 2018

European Journal of Endocrinology

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Objectives ACROSTUDY is an international, non-interventional study of acromegaly patients treated with pegvisomant (PEGV), a growth hormone receptor antagonist and has been conducted since 2004 in 15 countries to study the long-term safety and efficacy of PEGV. This report comprises the second interim analysis of 2090 patients as of May 12, 2016. Methods Descriptive analyses of safety, pituitary imaging and outcomes on PEGV treatment up to 12 years were performed. Results Prior to starting PEGV, 96% of patients had reported surgery, radiation, medical therapy or any combinations of those. At start of PEGV, 89% of patients had IGFI levels above the upper limit of normal (ULN). The percentage of patients with normal IGFI levels increased from 53% at year 1 to 73% at year 10, and the average daily dose of PEGV increased from 12.8 mg (year 1) to 18.9 mg (year 10). A total of 4832 adverse events (AEs) were reported in 1137 patients (54.4%), of which 570 were considered treatment related in 337 patients (16.1%). Serious AEs were reported in 22% of patients, of which 2.3% were considered treatment related. Locally reported MRIs showed most patients (72.2%) had no change in tumor size relative to the prior scan; 16.8% had a decrease, 6.8% an increase and 4.3% both. In patients with normal liver tests at PEGV start, an ALT or AST elevation of >3× ULN at any time point during their follow-up was reported in 3%. Conclusions This second interim analysis confirms that long-term use of PEGV is an effective and safe treatment in patients with acromegaly.

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“…Moreover, German and Japanese studies in 2007 [ 22 ] and 2016 [ 23 ] found the same results with improvement in clinical signs and symptoms after starting pegvisomant therapy; however, the previous three studies were designed to assess improvement in symptoms after treatment rather than persistence or comparison between patients with controlled and uncontrolled disease as with the present study, which assesses, using a cross-sectional design, the real-life correlation between different clinical and biochemical parameters at a point in time.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Clinical and Biochemical Markers in Patients With Acromegaly on Different Modalities of Treatment

Alzajaji¹,

Alidrisi²,

Mansour³

2021

Cureus

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Background Acromegaly is a disabling disease caused by growth hormone (GH) over-secretion, associated with increased morbidity and mortality through different metabolic and somatic consequences involving soft tissue, acral overgrowth, and skin thickening, which will lead to different clinical manifestations. The study aimed to assess the correlation between biochemical markers of acromegaly with different clinical findings and biochemical control with the clinical findings. Methods A cross-sectional study was done on 56 patients with acromegaly attending a tertiary center for diabetes, endocrine, and metabolism in Southern Iraq Basrah. They were 32 (57.1%) males. Fatigue, headache, excessive sweating, joint pain, backache, soft tissue swelling, numbness, snoring, and visual problems were assessed on a four-point Likert scale. In addition, biochemical dynamic GH testing was done using a five-point random GH curve and/or standard GH suppression under the oral glucose tolerance test (OGTT). Results No significant correlation was found between symptoms severity and five-point GH parameters in respect of mean, peak, and nadir. Only backache showed a significant correlation with GH under OGTT suppression parameters in respect to mean, peak, and nadir (P-values < 0.01, < 0.01, and < 0.01), respectively. No particular biochemical control cut-off value in the 9 am random GH, mean five-point GH curve, or nadir GH under OGTT was correlated with the degree of severity for any of the clinical symptoms, as there was no difference between the biochemically controlled and uncontrolled groups in respect to any of the clinical symptom’s severity scale. Conclusion Only backache correlated with the biochemical tests of disease activity in the form of GH under OGTT. It appears in this study that the severity of the clinical symptoms does not correlate with biochemical control so that thorough evaluation and treatment of clinical complaints besides biochemical control is an essential part of the management plan in patients with acromegaly.

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Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly

Cited by 11 publications

References 16 publications

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY

Correlation Between Clinical and Biochemical Markers in Patients With Acromegaly on Different Modalities of Treatment

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