Cost-effectiveness of Becaplermin for Nonhealing Neuropathic Diabetic Foot Ulcers

  • Wed, 9/3/08 - 10:25am
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Author(s): 
R. Gary Sibbald, MD, FRCPC; George Torrance, PhD; Margaret Hux, MSc; Cheryl Attard, MSc; and Natalie Milkovich, MSc

F oot ulcers are a common complication of diabetes. People with diabetes have a 15% lifetime ulcer risk1 and an estimated community prevalence of 2% to 5% of the diabetic population.2-5 Peripheral neuropathy and vascular disease are the primary factors contributing to ulcer development,6,7 which along with infection contribute to difficulty in healing. Ulcers failing to heal require daily dressing changes; involve functional limitations, inconvenience, and worry; and may result in costly and occasionally devastating consequences such as gangrene, infection, and amputation.1

Appropriate management can prevent or heal foot ulcers; thereby, reducing the risk of amputation.8 Best clinical care includes treating the ulcer cause and providing local ulcer care.6,9,10 Vascular insufficiency, if present, should be corrected with bypass or angioplasty. Patients should be followed to ensure proper diabetic control, systemic treatment of infection, proper foot care, and local pressure offloading with appropriate orthotic, casting, or non-weight bearing regimens. Local ulcer care includes active surgical debridement at frequent intervals (this alone has been shown to increase healing rates11) and provision of a moist interactive wound-healing environment.10,12,13

Even with appropriate management, ulcers may become chronic and fail to heal. Becaplermin, a platelet-derived growth factor in a hydrogel vehicle, stimulates cellular growth and migration of granulation tissue, thereby promoting healing. In a 20-week, double-blind multicenter phase III clinical trial, patients with diabetes, adequate vasculature, and infection-free chronic ulcers that did not probe to bone were randomized to receive best clinical care with once-daily applications of 100 microgram/g becaplermin gel (N=124 patients) or placebo vehicle gel (N= 127) for 20 weeks or until healing. Patients using becaplermin had a greater chance of 100% ulcer closure by 20 weeks (62 of 124 patients, 50%) than patients receiving vehicle gel alone (44 of 127 patients, 35%, 43% improvement; P = 0.007). For patients whose ulcers did close, time to healing was shorter with becaplermin (35th percentile 86 days versus 127 days, P = 0.013), while groups did not differ significantly in adverse events or recurrence.11,14 In a post-hoc analysis, patients who responded to treatment (30% ulcer closure) after 2 months of treatment showed a much higher probability of healing by 20 weeks (62% of responders healed versus 1% of non-responders).

In the current healthcare environment, decision-makers need clinical effectiveness and cost information. The objective of the current study, based on economic evaluation guidelines,15,16 was to estimate incremental cost-effectiveness (additional cost for each ulcer day averted) associated with adding becaplermin to best clinical care for the treatment of non-healing ulcers in patients with adequately controlled diabetes, adequate oxygen supply to surrounding tissue, and no infection or nonvitalized tissue in the ulcer.

References: 

1. American Diabetes Association. Consensus development conference on diabetic foot wound care (consensus statement). Diabetes Care. 1999;22:1354-1360.
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