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

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Creator
  • Phillips, Lawrence S.
    • Other Affiliation: Emory University School of Medicine, Atlanta, GA, USA
  • Herman-Bonert, Vivien
    • Other Affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • Strasburger, Christian J.
    • Other Affiliation: Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany
  • Stavrou, Stavros
    • Other Affiliation: New York University Medical Center, New York, NY, USA
  • Zib, Kenneth A.
    • Other Affiliation: Sensus Drug Development Corporation, Austin, TX, USA
  • Johannsson, Gudmundur
    • Other Affiliation: Såhlgrenska University Hospital, Goteborg, Sweden
  • Friend, Keith E.
    • Other Affiliation: University of Texas M D Anderson Cancer Center, Houston, TX, USA
  • Trainer, Peter J.
    • Other Affiliation: Christie Hospital, Manchester, UK
  • Thorner, Michael O.
    • Other Affiliation: University of Virginia Health Sciences Center, Charlottesville, VA, USA
  • Davis, Robert J.
    • Other Affiliation: Sensus Drug Development Corporation, Austin, TX, USA
  • Besser, G. Michael
    • Other Affiliation: St Bartholomew’s Hospital, London, UK
  • Stewart, Paul M.
    • Other Affiliation: Queen Elizabeth Hospital, Birmingham, UK
  • Melmed, Shlomo
    • Other Affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • Vance, Mary Lee
    • Other Affiliation: University of Virginia Health Sciences Center, Charlottesville, VA, USA
  • van der Lely, Aart Jan
    • Other Affiliation: Erasmus Medical Centre Rotterdam, 40 Dr Molewaterplein, 3015 GD Rotterdam, Netherlands
  • Clemmons, David
    • Affiliation: School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism
  • Hackett, Suzanne
    • Other Affiliation: StatWorks Inc, Chapel Hill, NC, USA
  • Barkan, Ariel L.
    • Other Affiliation: University of Michigan Medical Center, Ann Arbor, MI, USA
  • Cook, David M.
    • Other Affiliation: Oregon Health Sciences University, Portland, OR, USA
  • Scarlett, John A.
    • Other Affiliation: Sensus Drug Development Corporation, Austin, TX, USA
  • Klibanski, Anne
    • Other Affiliation: Massachusetts General Hospital, Boston, MD, USA
  • Katznelson, Laurence
    • Other Affiliation: Massachusetts General Hospital, Boston, MD, USA
  • Freda, Pamela U.
    • Other Affiliation: Columbia College of Physicians and Surgeons, New York, NY, USA
  • Hutson, R. Kent
    • Other Affiliation: University of Tennessee, Knoxville, TN, USA
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 μg/L (SE 24), 526 μg/L (29), and 523 μg/L (40) in patients treated for 6, 12 and 18 months, respectively (p less than 0·001), whereas growth hormone increased by 12·5 μg/L (2·1), 12·5 μg/L (3·0), and 14·2 μg/L (5·7) (p less than 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 μg/L (2·5) at baseline, rose to 15·2 μg/L (2·4) on drug, and fell back within 30 days of withdrawal to 8·3 μg/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 less than 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 cm3(0·057; p=0·353). Interpretation Pegvisomant is an effective medical treatment for acromegaly."
Date of publication
Identifier
  • 2-s2.0-0035944825
  • doi:10.1016/S0140-6736(01)06844-1
Related resource URL
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Lancet
Journal volume
  • 358
Journal issue
  • 9295
Page start
  • 1754
Page end
  • 1759
Language
  • English
Version
  • Postprint
ISSN
  • 0140-6736
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