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Benefit-Risk Assessment of Becaplermin in the Treatment of Diabetic Foot Ulcers

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Abstract

Becaplermin is a recombinant platelet-derived growth factor composed of two B chains that is approved for the treatment of neuropathic diabetic foot ulcers extending into or beyond the subcutaneous tissue in patients with adequate arterial perfusion. The aim of this review is to assess the benefits and risks associated with the use of this agent. Randomized controlled trials have provided evidence for the efficacy of becaplermin in increasing healing rates, and cost analyses have repeatedly shown a favourable cost-effectiveness ratio. However, clinical experience has not met these high expectations and becaplermin is not widely used. Moreover, this agent has not been compared with other additional treatment modalities, notably bioengineered skin substitutes and extracellular matrix proteins, and such comparisons are eagerly awaited. Of particular note, increased cancer risk has been reported in patients treated with more than three tubes of becaplermin; thus, this agent should be used only when the anticipated benefits outweigh the potential harm, and with extreme caution in patients with diagnosed malignancy. Finally, longer follow-up data are necessary to shed more light on the potential risk of malignancy in connection with becaplermin use.

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References

  1. Bakker K, Foster AVM, van Houtoum WH, et al. Time to act. Amsterdam: International Diabetes Federation and International Working Group on the Diabetic Foot, 2005

  2. Boulton AJM. The diabetic foot: grand overview, epidemiology and pathogenesis. Diabetes Metab Res Rev 2008; 24 Suppl. 1: S3–6

    Article  PubMed  Google Scholar 

  3. Edmonds M. The diabetic foot, 2003. Diabetes Metab Res Rev 2004; 20 Suppl. 1: S9–12

    Article  PubMed  Google Scholar 

  4. Papanas N, Maltezos E. The diabetic foot: established and emerging treatments. Acta Clin Belg 2007; 62: 230–8

    PubMed  CAS  Google Scholar 

  5. Reiber GE, Vileikyte L, Boyko EJ, et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 1999; 22: 157–62

    Article  PubMed  CAS  Google Scholar 

  6. Reiber GE, Ledoux WR. Epidemiology of diabetic foot ulcers and complications: evidence for prevention. In: Williams R, Herman W, Kinmoth AL, et al., editors. The evidence base for diabetes care. Chichester: Wiley, 2002: 641–65

    Chapter  Google Scholar 

  7. Boulton AJM. The diabetic foot: from art to science. The 18th Camillo Golgi lecture. Diabetologia 2004; 47: 1343–53

    Article  PubMed  CAS  Google Scholar 

  8. Papanas N, Maltezos E. Becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Clin Interv Aging 2008; 3: 233–40

    PubMed  CAS  Google Scholar 

  9. Fang RC, Galiano RD. A review of becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Biologics 2008; 2: 1–12

    PubMed  CAS  Google Scholar 

  10. Piascik P. Use of Regranex gel for diabetic foot ulcers. J Am Pharm Assoc 1998; 38: 628–30

    CAS  Google Scholar 

  11. Papanas N, Maltezos E. Growth factors in the treatment of diabetic foot ulcers: new technologies, any promises? Int J Low Extrem Wounds 2007; 6: 37–53

    Article  PubMed  CAS  Google Scholar 

  12. US prescribing information for Regranex [online]. Available from URL: http://www.regranex.com/Prescribing%20Info. php [Accessed 2010 Mar 16]

  13. International Working Group on the Diabetic Foot. International consensus on the diabetic foot and practical guidelines on the management and prevention of the diabetic foot. Amsterdam: International Working Group on the Diabetic Foot, 2007

    Google Scholar 

  14. Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg 1995; 21: 71–81

    Article  PubMed  CAS  Google Scholar 

  15. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers: a phase III randomized placebo-controlled double-blind study. Diabetes Care 1998; 21: 822–7

    Article  PubMed  CAS  Google Scholar 

  16. D’Hemercourt PA, Smiell JM, Karim MR. Effect of sodium carbomethylcellulose aqueous-based gel versus becaplermin gel in patients with non-healing lower extremity diabetic ulcers. Wounds 1998; 10: 69–75

    Google Scholar 

  17. Embil JM, Papp K, Sibblad G, et al. Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of safety. Wound Rep Reg 2000; 8: 162–8

    Article  CAS  Google Scholar 

  18. Margolis DJ, Bartus C, Hoffstad O, et al. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Wound Rep Reg 2005; 13: 531–6

    Article  Google Scholar 

  19. Bhansali A, Venkatesh S, Dutta P, et al. Which is the better option: recombinant human PDGF-BB 0.01% gel or standard wound care, in diabetic neuropathic large plantar ulcers off-loaded by a customized contact cast? Diabetes Res Clin Pract 2009; 83: e13–6

    Article  PubMed  CAS  Google Scholar 

  20. Hardikar JV, Reddy YC, Bung DD, et al. Efficacy of recombinant human platelet-derived growth factor (rhPDGF) based gel in diabetic foot ulcers: a randomized, multicenter, double-blind, placebo-controlled study in India. Wounds 2005; 17: 141–52 461

    Google Scholar 

  21. Papanas N, Maltezos E, Edmonds M. St. Vincent declara-tion after 15 years or who cleft the devil’s foot? Vasa 2006; 35: 3–4

    Article  PubMed  CAS  Google Scholar 

  22. Margolis DJ, Kantor J, Santanna J, et al. Risk factors for delayed healing of neuropathic diabetic foot ulcers. Arch Dermatol 2000; 136: 1531–5

    Article  PubMed  CAS  Google Scholar 

  23. Boulton AJM, Kirsner RS, Vileikyte L. Neuropathic diabetic foot ulcers. N Engl J Med 2004; 351: 48–55

    Article  PubMed  CAS  Google Scholar 

  24. Margolis DJ, Allen-Taylor L, Hoffstad O, et al. Healing diabetic neuropathic foot ulcers: are we getting better? Diabet Med 2005; 22: 172–6

    Article  PubMed  CAS  Google Scholar 

  25. Jude EB, Blakytny R, Bulmer J, et al. Transforming growth factor-beta 1,2,3 and receptor type I and II in diabetic foot ulcers. Diabet Med 2002; 19: 440–7

    Article  PubMed  CAS  Google Scholar 

  26. Blakytny R, Jude EB, Martin Gibson J, et al. Lack of insulin-like growth factor 1 (IGF-1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. J Pathol 2000; 190: 589–94

    Article  PubMed  CAS  Google Scholar 

  27. Duraisamy Y, Slevin M, Smith N, et al. Effect of glycation on basic fibroblast growth factor-induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes. Angiogenesis 2001; 4: 277–88

    Article  PubMed  CAS  Google Scholar 

  28. Black E, Vibe-Pedersen J, Jorgensen LN, et al. Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control. Arch Surg 2003; 138: 34–40

    Article  PubMed  CAS  Google Scholar 

  29. Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med 2006; 23: 594–608

    Article  PubMed  CAS  Google Scholar 

  30. Jeffcoate W, Price P, Harding KG. Wound healing and treatments for people with diabetic foot ulcers. Diabetes Metab Res Rev 2004; 20 Suppl. 1: S78–89

    Article  PubMed  Google Scholar 

  31. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 2005; 366: 1736–43

    Article  PubMed  Google Scholar 

  32. Smiell JM, Wieman TJ, Steed DL, et al. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Rep Reg 1999; 7: 335–46

    Article  CAS  Google Scholar 

  33. Persson U, Willis M, Ödegaard K, et al. The cost-effectiveness of treating diabetic lower extremity ulcers with becaplermin (Regranex): a core model with an application using Swedish cost data. Val Health 2000; 3 Suppl. 1: S39–46

    Article  Google Scholar 

  34. Ghatnekar O, Persson U, Willis M, et al. The costeffectiveness in the UK of treating diabetic lower extremity ulcers with becaplermin gel. J Drug Assess 2000; 3: 243–51

    Google Scholar 

  35. Ghatnekar O, Persson U, Willis M, et al. Cost effectiveness of becaplermin in the treatment of diabetic foot ulcers in four European countries. Pharmacoeconomics 2001; 19: 767–78

    Article  PubMed  CAS  Google Scholar 

  36. Kantor J, Margolis DJ. Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness analysis. Dermatol Surg 2001; 27: 347–51

    Article  PubMed  CAS  Google Scholar 

  37. Albert S. Cost-effective management of recalcitrant diabetic foot ulcers. Clin Podiatr Med Surg 2002; 19: 483–91

    Article  PubMed  Google Scholar 

  38. Sibbald RG, Torrance G, Hux M, et al. Cost-effectiveness of becaplermin for nonhealing neuropathic diabetic foot ulcers. Ostomy Wound Manage 2003; 49: 76–84

    PubMed  Google Scholar 

  39. Lantis II JC, Boone D, Gendics C, et al. Analysis of patient cost for recombinant human platelet-derived growth factor therapy as the first-line treatment of the insured patient with a diabetic foot ulcer. Adv Skin Wound Care 2009; 22: 167–71

    Article  PubMed  Google Scholar 

  40. Smiell JM. Clinical safety of becaplermin (rhPDGF-BB) gel. Am J Surg 1998; 176 Suppl. 2A: 68–73S

    Article  Google Scholar 

  41. Shi J, Chen T, Tian H. Efficacy and safety of recombinant human platelet-derived growth factor gel for diabetic neuropathic foot ulcers: a systematic review. Diabetologia 2009; 52 Suppl. 1: A1157

    Google Scholar 

  42. US FDA. Update of safety review: follow-up to the March 27, 2008, communication about the ongoing safety review of Regranex (becaplermin) [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm072148.htm [Accessed 2009 Oct 7]

  43. Petrova N, Edmonds M. Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs 2006; 11: 709–24

    Article  PubMed  CAS  Google Scholar 

  44. Topical becaplermin: cancer. Think twice before using it. Rev Prescrire 2008; 28: 430

    Google Scholar 

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Acknowledgements

No sources of funding have been used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Outpatient Clinic of the Diabetic Foot, Second Department of Internal Medicine, Democritus University of Thrace, G. Kondyli 22, Alexandroupolis, 68100, Greece

    DrNikolaos Papanas & Efstratios Maltezos

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  1. DrNikolaos Papanas
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  2. Efstratios Maltezos
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Correspondence to DrNikolaos Papanas.

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Papanas, D., Maltezos, E. Benefit-Risk Assessment of Becaplermin in the Treatment of Diabetic Foot Ulcers. Drug-Safety 33, 455–461 (2010). https://doi.org/10.2165/11534570-000000000-00000

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