Diabetic foot Ulcer Treatment
The therapeutic management of patients with a diabetic foot ulcer (DFU) is currently based on:
- Relief of pressure.
- Restoring skin perfusion.
- Treating and controlling infection.
- Metabolic control.
- Co-morbidity managements.
Local wound care:
-Examine ulcer evolution frequently.
-Debride the ulcer.
-Select good ulcer care procedure according to international approved by medical standards.
-Prevention of recurrence. - Provide effective patient and family education.
EPIDERMAL GROWTH FACTOR, A REPLACEMENT THERAPY TO TREAT DIABETIC FOOT ULCER
Epidermal growth factor (EGF) is a 53 amino acid polypeptide
isolated for the first time from mice submaxillary glands by Stanley Cohen. It stimulates fibroblasts, keratinocytes and
vascular endothelial cells proliferation that improve high quality new granulation tissue and wound healing. The healing mechanisms start with the coupling of EGF with specific receptors located on the cellular membrane.
EGF receptors are glycoproteins with an extracellular binding domain, a transmembrane region and a cytoplasmic portion with tyrosine kinase activity. EGF receptors are expressed on most human cell types including those that play critical roles in wound repair such as fibroblasts, endothelial cells and keratinocytes.
THE RATIONALE OF EGF USE TO TREAT DIABETIC FOOT ULCERS
- Impairment of healing in diabetic patients, associated with a relative deficit of growth factors
(EGF among them). - Role of EGF in stimulating not only angiogenesis but also cell division, differentiation and
migration in damaged tissues and wounds.
Why EGF has to be intralesionally injected?
- The availability of the growth factor at wound surface is limited.
- Bacterial biofilm is a physical barrier that limit and affect added healing medications with cell
receptors. - Wound area is rich in acute proteases that can degrade quite fast any added healing medication.
- Cells at the deep tissue layers are richer in EGF receptors when compared with epidermal and surface cell tissues.
WHERE TO INJECT EGF?
Injecting EGF deep into the wound base and contours would allow larger pharmacodynamics response in terms of high quality and faster new granulation tissue formation and as consequence better and faster wound closure.
KEY FACTS OF INFILTRATION METHODOLOGY
- Deposit t EGF in the wound deep extracellular matrix.
- Reduce EGF exposition to the superficial bacterial biofilm avoiding in parallel proteolysis due to
prolonged acute protease expositions released at wound surfaces. - Favor an adequate local EGF access to cells at the deep tissue layers that are richer in EGF
receptors when compared with epidermal and surface cell tissues - Stimulate the ascending granulation and the contraction of wound by mimicking natural wound
healing process.
Clinical trials and post marketing experience
Exploratory and confirmatory clinical trials have been completed in patients with advanced DFU and high amputation risk (reviewed in reference 4).
Properties and advantages of Heberprot-P®
- Stimulates the development of new granulation tissue accelerating re-epithelization, scar formation and wound healing in diabetic foot ulcers.
- Reduces time for healing.
- Reduces risk of amputation.
Post marketing active surveillance was initiated to evaluate drug effectiveness and safety.
Efficacy results in clinical trials (pooled) and pharmacovigilance experiences of Heberprot-P® (Intralesional rhEGF) in patients with DFU
Lesion treated with Heberprot-P®
OVERVIEW OF SAFETY
Most frequent adverse events pharmaco-surveillance
Recombinant EGF when applied on diabetic ulcers have been well tolerated showing a safe profile.
Around half of the patients (63.1% in the clinical trials and 46.2% in the post marketing) reported of adverse event.
IMPACT STUDIES IN CUBA
Three observational, retrospective and descriptive epidemiological studies were carried out in 8 Cuban hospitals. The objective was to evaluate the benefits of Heberprot-P® treatment in the patient outcomes, regarding major amputations. As shown in the figure below, groups of patients treated with Heberprot-P® evidenced a low amputation rate of 5.5%. Compared to groups not treated with the treatment but only with general standard care showing higher amputation rates, 29.6%.
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