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

被引:438
作者
van der Lely, AJ
Hutson, RK
Trainer, PJ
Besser, GM
Barkan, AL
Katznelson, L
Klibanski, A
Herman-Bonert, V
Melmed, S
Vance, ML
Freda, PU
Stewart, PM
Friend, KE
Clemmons, DR
Johannsson, G
Stavrou, S
Cook, DM
Phillips, LS
Strasburger, CJ
Hacker, S
Zib, KA
Davis, RJ
Scarlett, JA
Thorner, M
机构
[1] Erasmus MC, NL-3015 GD Rotterdam, Netherlands
[2] Univ Tennessee, Knoxville, TN USA
[3] Christie Hosp, Manchester, Lancs, England
[4] St Bartholomews Hosp, London, England
[5] Univ Michigan, Med Ctr, Ann Arbor, MI USA
[6] Massachusetts Gen Hosp, Boston, MA 02114 USA
[7] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[8] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA
[9] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA
[10] Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England
[11] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
[12] Univ N Carolina, Sch Med, Chapel Hill, NC USA
[13] Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden
[14] NYU, Med Ctr, New York, NY 10016 USA
[15] Oregon Hlth & Sci Univ, Portland, OR 97201 USA
[16] Emory Univ, Sch Med, Atlanta, GA USA
[17] Univ Munich, Klinikum Innenstadt, D-8000 Munich, Germany
[18] StatWorks Inc, Chapel Hill, NC USA
[19] Sensus Drug Dev Corp, Austin, TX USA
关键词
D O I
10.1016/S0140-6736(01)06844-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulinlike 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 mug/L (SE 24), 526 mug/L (29), and 523 mug/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 <mu>g/L (2.1), 12.5 mug/L (3.0), and 14.2 mug/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 <mu>g/L (2.5) at baseline, rose to 15.2 mug/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mug/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.
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收藏
页码:1754 / 1759
页数:6
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