Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82061
Title:
Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
Authors:
Van der Lely, A J; Hutson, R K; Trainer, Peter J; Besser, G M; Barkan, Ariel L; Katznelson, L; Klibanski, Anne; Herman-Bonert, V; Melmed, Shlomo; Vance, Mary Lee; Freda, P U; Stewart, P M; Friend, K E; Clemmons, David R; Johannsson, G; Stavrou, S; Cook, D M; Phillips, L S; Strasburger, Christian J; Hackett, S; Zib, K A; Davis, R J; Scarlett, J A; Thorner, Michael O
Abstract:
BACKGROUND: Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. METHODS: Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. FINDINGS: Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353). INTERPRETATION: Pegvisomant is an effective medical treatment for acromegaly.
Affiliation:
Erasmus Medical Centre Rotterdam, 40 Dr Molewaterplein, 3015 GD, Rotterdam, Netherlands. vanderlely@inw3.azr.nl
Citation:
Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. 2001, 358 (9295):1754-9 Lancet
Journal:
Lancet
Issue Date:
24-Nov-2001
URI:
http://hdl.handle.net/10541/82061
DOI:
10.1016/S0140-6736(01)06844-1
PubMed ID:
11734231
Type:
Article
Language:
en
ISSN:
0140-6736
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorVan der Lely, A J-
dc.contributor.authorHutson, R K-
dc.contributor.authorTrainer, Peter J-
dc.contributor.authorBesser, G M-
dc.contributor.authorBarkan, Ariel L-
dc.contributor.authorKatznelson, L-
dc.contributor.authorKlibanski, Anne-
dc.contributor.authorHerman-Bonert, V-
dc.contributor.authorMelmed, Shlomo-
dc.contributor.authorVance, Mary Lee-
dc.contributor.authorFreda, P U-
dc.contributor.authorStewart, P M-
dc.contributor.authorFriend, K E-
dc.contributor.authorClemmons, David R-
dc.contributor.authorJohannsson, G-
dc.contributor.authorStavrou, S-
dc.contributor.authorCook, D M-
dc.contributor.authorPhillips, L S-
dc.contributor.authorStrasburger, Christian J-
dc.contributor.authorHackett, S-
dc.contributor.authorZib, K A-
dc.contributor.authorDavis, R J-
dc.contributor.authorScarlett, J A-
dc.contributor.authorThorner, Michael O-
dc.date.accessioned2009-09-22T11:46:38Z-
dc.date.available2009-09-22T11:46:38Z-
dc.date.issued2001-11-24-
dc.identifier.citationLong-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. 2001, 358 (9295):1754-9 Lanceten
dc.identifier.issn0140-6736-
dc.identifier.pmid11734231-
dc.identifier.doi10.1016/S0140-6736(01)06844-1-
dc.identifier.urihttp://hdl.handle.net/10541/82061-
dc.description.abstractBACKGROUND: Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. METHODS: Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. FINDINGS: Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353). INTERPRETATION: Pegvisomant is an effective medical treatment for acromegaly.en
dc.language.isoenen
dc.subject.meshAcromegaly-
dc.subject.meshAdult-
dc.subject.meshBlood Glucose-
dc.subject.meshCohort Studies-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFemale-
dc.subject.meshGrowth Hormone-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshReceptors, Somatotropin-
dc.titleLong-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.en
dc.typeArticleen
dc.contributor.departmentErasmus Medical Centre Rotterdam, 40 Dr Molewaterplein, 3015 GD, Rotterdam, Netherlands. vanderlely@inw3.azr.nlen
dc.identifier.journalLanceten

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