Advanced Biologics for Diabetic Foot Ulcers Effective, but Delayed

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.