Recombinant Human Platelet-Derived Growth Factor-BB
Recombinant Human Platelet-Derived Growth Factor-BB
Objective: Two randomized, placebo-controlled, pilot studies were conducted to evaluate the efficacy and safety of becaplermin gel 100mg/g (rhPDGF-BB; Regranex® 0.01%, Johnson & Johnson Wound Management Worldwide, Somerville, New Jersey) in patients ≥18 years of age with chronic venous ulcers.
Methods: Patients were treated with becaplermin gel 100mg/g (Study 1, n = 35; Study 2, n = 32) or placebo gel (Study 1, n = 36; Study 2, n = 32) for a maximum of 16 weeks or until ulcers were completely healed, whichever came first. Study medication was applied to the ulcers daily (in Study 1) or twice weekly (Study 2), and the ulcers were covered with nonadherent dressing with or without gauze. All patients received a standardized regimen of good wound care, including sharp debridement, compression therapy, and infection control. Efficacy measures included the incidence of and time to complete healing. The incidence of adverse events was used to evaluate safety.
Results: In Study 1, complete healing occurred in 36 percent (12/35) of patients treated with becaplermin gel compared with 34 percent (12/36) of patients treated with placebo gel. In Study 2, complete healing was noted in 56 percent (18/32) of patients treated with becaplermin gel compared with 44 percent (14/32) of patients treated with placebo. Further analysis showed that becaplermin gel was of greater benefit in patients with baseline ulcer size of ≥5cm2. The incidence of adverse events (overall and treatment-emergent, wound-related) was generally comparable for both treatment groups in each study.
Conclusion: These results suggest that becaplermin gel 100mg/g in conjunction with good wound care that includes compression therapy at 30 to 40mmHg appears safe and may be beneficial in the treatment of patients with chronic venous leg ulcers, whether used daily or twice weekly. An additional large-scale study will be necessary for conclusive determination of efficacy.
The exact prevalence of venous ulcers is unknown, but estimates from the United States suggest that between 600,000 and 2.5 million individuals in the US suffer from these chronic, debilitating wounds, while estimates indicate that between 0.15 percent and 1 percent of the European population suffer from this condition. Thus, venous ulceration represents a common problem, particularly in the elderly population.
Venous ulcers are associated with a significant disease burden, as these ulcers are painful, are difficult to heal, and recur frequently. Current treatments range from compression therapy with stockings and bandages (to improve venous circulation) to skin grafting (to accelerate healing) and surgery to correct the underlying cause of venous insufficiency. Therefore, treatment strategies for venous ulcers are associated with substantial medical costs. The indirect costs of venous ulceration can be substantial as well: an estimated two million work days are lost each year in the US because of leg ulcers.
Although the etiology of venous ulceration is unclear, it has been suggested that ulceration results from increased intraluminal pressure in the capillaries, which in turn results in the deposition of fibrin around the capillaries. Subsequently, white blood cells (WBCs) become activated and release proteolytic enzymes, which may cause further tissue destruction. According to the "trap" hypothesis, which is another proposed mechanism, fibrin and other macromolecules eventually leak into the dermis where they bind to growth factors, making them unavailable for the tissue repair process. This hypothesis suggests a potential role for topically applied growth factors in the treatment of venous ulcers.
Platelet-derived growth factor (PDGF) plays an important role in the initiation and regulation of the healing process. Specifically, PDGF promotes the chemotactic recruitment and proliferation of cells involved in all stages of wound repair and enhances the formation of granulation tissue. Recombinant human PDGF-BB (rhPDGF-BB) has activity similar to that of endogenous PDGF and has been shown to increase the incidence of complete healing of chronic wounds (i.e., diabetic foot ulcers and pressure ulcers) in several clinical studies.
Taken together, these findings suggest that rhPDGF-BB may be of benefit in patients with venous ulcers as well. This paper describes the results of two pilot studies conducted to evaluate the efficacy and safety of topically applied becaplermin gel (rhPDGF-BB; Regranex® 0.01%, Johnson & Johnson Wound Management Worldwide, Somerville, New Jersey) in patients with chronic, full-thickness, venous stasis leg ulcers.
Objective: Two randomized, placebo-controlled, pilot studies were conducted to evaluate the efficacy and safety of becaplermin gel 100mg/g (rhPDGF-BB; Regranex® 0.01%, Johnson & Johnson Wound Management Worldwide, Somerville, New Jersey) in patients ≥18 years of age with chronic venous ulcers.
Methods: Patients were treated with becaplermin gel 100mg/g (Study 1, n = 35; Study 2, n = 32) or placebo gel (Study 1, n = 36; Study 2, n = 32) for a maximum of 16 weeks or until ulcers were completely healed, whichever came first. Study medication was applied to the ulcers daily (in Study 1) or twice weekly (Study 2), and the ulcers were covered with nonadherent dressing with or without gauze. All patients received a standardized regimen of good wound care, including sharp debridement, compression therapy, and infection control. Efficacy measures included the incidence of and time to complete healing. The incidence of adverse events was used to evaluate safety.
Results: In Study 1, complete healing occurred in 36 percent (12/35) of patients treated with becaplermin gel compared with 34 percent (12/36) of patients treated with placebo gel. In Study 2, complete healing was noted in 56 percent (18/32) of patients treated with becaplermin gel compared with 44 percent (14/32) of patients treated with placebo. Further analysis showed that becaplermin gel was of greater benefit in patients with baseline ulcer size of ≥5cm2. The incidence of adverse events (overall and treatment-emergent, wound-related) was generally comparable for both treatment groups in each study.
Conclusion: These results suggest that becaplermin gel 100mg/g in conjunction with good wound care that includes compression therapy at 30 to 40mmHg appears safe and may be beneficial in the treatment of patients with chronic venous leg ulcers, whether used daily or twice weekly. An additional large-scale study will be necessary for conclusive determination of efficacy.
The exact prevalence of venous ulcers is unknown, but estimates from the United States suggest that between 600,000 and 2.5 million individuals in the US suffer from these chronic, debilitating wounds, while estimates indicate that between 0.15 percent and 1 percent of the European population suffer from this condition. Thus, venous ulceration represents a common problem, particularly in the elderly population.
Venous ulcers are associated with a significant disease burden, as these ulcers are painful, are difficult to heal, and recur frequently. Current treatments range from compression therapy with stockings and bandages (to improve venous circulation) to skin grafting (to accelerate healing) and surgery to correct the underlying cause of venous insufficiency. Therefore, treatment strategies for venous ulcers are associated with substantial medical costs. The indirect costs of venous ulceration can be substantial as well: an estimated two million work days are lost each year in the US because of leg ulcers.
Although the etiology of venous ulceration is unclear, it has been suggested that ulceration results from increased intraluminal pressure in the capillaries, which in turn results in the deposition of fibrin around the capillaries. Subsequently, white blood cells (WBCs) become activated and release proteolytic enzymes, which may cause further tissue destruction. According to the "trap" hypothesis, which is another proposed mechanism, fibrin and other macromolecules eventually leak into the dermis where they bind to growth factors, making them unavailable for the tissue repair process. This hypothesis suggests a potential role for topically applied growth factors in the treatment of venous ulcers.
Platelet-derived growth factor (PDGF) plays an important role in the initiation and regulation of the healing process. Specifically, PDGF promotes the chemotactic recruitment and proliferation of cells involved in all stages of wound repair and enhances the formation of granulation tissue. Recombinant human PDGF-BB (rhPDGF-BB) has activity similar to that of endogenous PDGF and has been shown to increase the incidence of complete healing of chronic wounds (i.e., diabetic foot ulcers and pressure ulcers) in several clinical studies.
Taken together, these findings suggest that rhPDGF-BB may be of benefit in patients with venous ulcers as well. This paper describes the results of two pilot studies conducted to evaluate the efficacy and safety of topically applied becaplermin gel (rhPDGF-BB; Regranex® 0.01%, Johnson & Johnson Wound Management Worldwide, Somerville, New Jersey) in patients with chronic, full-thickness, venous stasis leg ulcers.
Source...