Moore, David J., Dr., Adi, Y., Connock, M. and Bayliss, Sue. (2009) Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation. BMC Endocrine Disorders, Vol.9 (Article 20). ISSN 1472-6823

PDF WRAP_Adi.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (450Kb)

Abstract

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was £81,000/QALY and £212,000/LYG. To reduce this to £30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Acromegaly -- Treatment -- Great Britain, Somatotropin -- Synthesis, Pituitary gland -- Tumors, Drugs -- Effectiveness -- Great Britain, Drugs -- Prices -- Great Britain
Journal or Publication Title:	BMC Endocrine Disorders
Publisher:	BioMed Central Ltd.
ISSN:	1472-6823
Date:	8 October 2009
Volume:	Vol.9
Number:	Article 20
Identification Number:	10.1186/1472-6823-9-20
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	West Midlands Primary Care Trusts' Levy (Great Britain) (WMPCTL), Pfizer Inc.
References:	1. Melmed S, Melmed S: Medical progress: Acromegaly. [Review] [102 refs]. New England Journal of Medicine 2006, 355:2558-2573. 2. Chanson P, Salenave S: Acromegaly. Orphanet J Rare Dis 2008, 3:17. 3. Colao A, Ferone D, Marzullo P, Lombardi G: Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004, 25:102-152. 4. Holdaway IM, Rajasoorya C: Epidemiology of acromegaly. Pituitary 1999, 2:29-41. 5. Pfizer Limited: Somavert: Summary of Product Characteristics. 2004 [http://emc.medicines.org.uk/medicine/14353/SPSOMA VERT+10mg%2c+15mg+%26+20mg+powder+and+solvent+ for+solution+for+injection/]. Accessed August 2007 6. NHS Centre for Reviews and Dissemination University of York: Undertaking systematic reviews of research on effectiveness: CRDs guidance for those carrying out or commisioning reviews. 4. 2nd edition. 2001. 7. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, Lely AJ van der, Dimaraki EV, Stewart PM, Friend KE, Vance ML: Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. The New England journal of medicine 2000, 342:1171-1177. 8. Lely AJ van der, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML: Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist[see comment]. Lancet 2001, 358:1754-1759. 9. Sesmilo G, Fairfield WP, Katznelson L, Pulaski K, Freda PU, Bonert V, Dimaraki E, Stavrou S, Vance ML, Hayden D: Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. The Journal of clinical endocrinology and metabolism 2002, 87:1692-1699. 10. Fairfield WP, Sesmilo G, Katznelson L, Pulaski K, Freda PU, Stavrou S, Kleinberg D, Klibanski A: Effects of a growth hormone receptor antagonist on bone markers in acromegaly. Clinical endocrinology 2002, 57:385-390. 11. Biering H, Saller B, Bauditz J, Pirlich M, Rudolph B, Johne A, Buchfelder M, Mann K, Droste M, Schreiber I: Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis. European Journal of Endocrinology 2006, 154:213-220. 12. Parkinson C, Burman P, Messig M, Trainer PJ, Parkinson C, Burman P, Messig M, Trainer PJ: Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. Journal of Clinical Endocrinology & Metabolism 2007, 92:190-195. 13. Paisley AN, O'Callaghan CJ, Lewandowski KC, Parkinson C, Roberts ME, Drake WM, Monson JP, Trainer PJ, Randeva HS, Paisley AN: Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly. Journal of Clinical Endocrinology & Metabolism 2006, 91:4635-4640. 14. Parkinson C, Flyvbjerg A, Trainer PJ: High levels of 150-kDa insulin- like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomantinduced serum IGF-I normalization. Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 2004, 14:59-65. 15. Parkinson C, Kassem M, Heickendorff L, Flyvbjerg A, Trainer PJ: Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. The Journal of clinical endocrinology and metabolism 2003, 88:5650-5655. 16. Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Burman P, Kourides IA, Strasburger CJ: Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. European Journal of Endocrinology 2006, 154:467-477. 17. Jehle S, Reyes CM, Sundeen RE, Freda PU, Jehle S, Reyes CM, Sundeen RE, Freda PU: Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly. Journal of Clinical Endocrinology & Metabolism 2005, 90:1588-1593. 18. Feenstra J, de Herder WW, ten Have SM, Beld AW van den, Feelders RA, Janssen JA, Lely AJ van der, Feenstra J, de Herder WW, ten Have SMTH: Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly[erratum appears in Lancet. 2005 May;365(9471):1620]. Lancet 2005, 365:1644-1646. 19. Jorgensen JO, Feldt-Rasmussen U, Frystyk J, Chen JW, Kristensen LO, Hagen C, Orskov H, Jorgensen JOL, Feldt-Rasmussen U, Frystyk J: Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist. Journal of Clinical Endocrinology & Metabolism 2005, 90:5627-5631. 20. Pivonello R, Galderisi M, Auriemma RS, De Martino MC, Galdiero M, Ciccarelli A, D'Errico A, Kourides I, Burman P, Lombardi G: Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance. Journal of Clinical Endocrinology & Metabolism 2007, 92:476-482. 21. Schreiber I, Buchfelder M, Droste M, Forssmann K, Mann K, Saller B, Strasburger CJ, the GPI, Schreiber I, Buchfelder M: Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study. European Journal of Endocrinology 2007, 156:75-82. 22. Parkinson C, Drake WM, Wieringa G, Yates AP, Besser GM, Trainer PJ, Parkinson C, Drake WM, Wieringa G, Yates AP: Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly. Clinical Endocrinology 2002, 56:303-311. 23. Parkinson C, Whatmore AJ, Yates AP, Drake WM, Brabant G, Clayton PE, Trainer PJ, Parkinson C, Whatmore AJ, Yates AP: The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly. Clinical Endocrinology 2003, 59:168-174. 24. Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, Lely AJ van der, Vance ML: Glucose homeostasis and safety in patients with acromegaly converted from longacting octreotide to pegvisomant. The Journal of clinical endocrinology and metabolism 2005, 90:5684-5691. 25. Paisley AN, Hayden K, Ellis A, Anderson J, Wieringa G, Trainer PJ: Pegvisomant interference in GH assays results in underestimation of GH levels. European Journal of Endocrinology 2007, 156:315-319. 26. Welsh Medicines Partnership: Therapeutic Development Assessment Pegvisomant (Somavert®). 2007 [http:// www.wales.nhs.uk/sites3/Documents/371/ Enc%203%20WMP%20Pegvisomant%20report.pdf]. Accessed June 2007 27. Bates AS, Van't HW, Jones JM, Clayton RN: An audit of outcome of treatment in acromegaly. Q J Med 1993, 86:293-299. 28. Orme SM, McNally RJ, Cartwright RA, Belchetz PE: Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 1998, 83:2730-2734. 29. Kauppinen-Makelin R, Sane T, Reunanen A, Valimaki MJ, Niskanen L, Markkanen H, Loyttyniemi E, Ebeling T, Jaatinen P, Laine H: A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab 2005, 90:4081-4086. 30. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS: Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab 2004, 89:1613-1617. 31. Rowles SV, Prieto L, Badia X, Shalet SM, Webb SM, Trainer PJ: Quality of life (QOL) in patients with acromegaly is severely impaired: use of a novel measure of QOL: acromegaly quality of life questionnaire. J Clin Endocrinol Metab 2005, 90:3337-3341. 32. Kauppinen-Makelin R, Sane T, Sintonen H, Markkanen H, Valimaki MJ, Loyttyniemi E, Niskanen L, Reunanen A, Stenman UH, Kauppinen- Makelin R: Quality of life in treated patients with acromegaly. Journal of Clinical Endocrinology & Metabolism 2006, 91:3891-3896. 33. Biermasz NR, van Thiel SW, Pereira AM, Hoftijzer HC, van Hemert AM, Smit JW, Romijn JA, Roelfsema F: Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess. J Clin Endocrinol Metab 2004, 89:5369-5376. 34. Hua SC, Yan YH, Chang TC, Hua SC, Yan YH, Chang TC: Associations of remission status and lanreotide treatment with quality of life in patients with treated acromegaly. European Journal of Endocrinology 2006, 155:831-837. 35. Webb SM, Badia X, Surinach NL, Spanish AcroQol Study Group: Validity and clinical applicability of the acromegaly quality of life questionnaire, AcroQoL: a 6-month prospective study. European Journal of Endocrinology 2006, 155:269-277. 36. Trepp R, Everts R, Stettler C, Fischli S, Allemann S, Webb SM, Christ ER: Assessment of quality of life in patients with uncontrolled vs. controlled acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL). Clin Endocrinol (Oxf) 2005, 63:103-110. 37. British National Formulary: 2007 [http://www.bnf.org/bnf/]. Accessed June 2007 38. NHS reference costs 2005-06, Mental Health Services: Inpatient Data. MHIPA2 adult: acute care 2007. Ref Type: Data File 39. Moore D, Meads C, Roberts L, Song F: The effectiveness of somatostatin analogues in the treatment of acromegaly. Report 37, West Midlands Health Technology Assessment Collaboration. Department of Public Health & Epidemiology, University of Birmingham 2001:1-74. Ref Type: Report 40. Cambridgeshire joint prescribing group decision document: Pegvisomant (Somavert, Pfizer) for treatment of acromegaly. 2006 [http://www.cambsphn.nhs.uk/docu mentCJPG%20InformatioDecisionPegvisomant%2%20Decision%20Ja n%202006.doc?pre ventCache=08%2F11%2F2006+16%3A14]. Accessed June 2007 41. Didoni G, Grottol S, Gasco V, Battistini M, Ferone D, Giusti M, Ragazzoni F, Ruffo P, Ghigo E, Minuto F: Cost-of-illness study in acromegalic patients in Italy. J Endocrinol Invest 2004, 27:1034-1039. 42. Bonert VS, Kennedy L, Petersenn S, Barkan A, Carmichael J, Melmed S: Lipodystrophy in patients with acromegaly receiving pegvisomant. J Clin Endocrinol Metab 2008, 93:3515-3518.
URI:	http://wrap.warwick.ac.uk/id/eprint/2679

Request changes to a record

Actions (login required)

View Item