Findings by SBU Alert

Version: 1

Technology and target group

Hard-to-heal lower leg and foot ulcers are common. This type of ulceration is a sign of underlying disease. The largest subgroup, ie, venous leg ulcers, is caused by impaired function in the venous blood flow (venous insufficiency) and comprises approximately 50 percent of all leg ulcers. Usually this type of leg ulcer continues to reappear over a longer period of time. The dominating therapy is compression treatment. Transplantation of the patients own tissue (autologous transplantation) is used to treat hard-to-heal ulcers, but new methods involving cultured skin have been developed that utilize other human tissue. A major advantage of this method, compared to autologous transplantation, is sparing the patient from treatment demanding skin defects secondary to graft skin harvesting. Apligraf® is one type of cultured human skin equivalent. This material is cultured from foreskin removed in the circumcision of newborn males. The process used to manufacture Apligraf® requires the method to be classified as a pharmaceutical product. The end product is delivered in special packaging and has a shelf life of 5 days. Treatment is provided on an outpatient basis and is generally repeated several times. The potential target group for skin transplantation as a result of hard-to-heal leg and foot ulcers in Sweden is estimated to be approximately 2 000 patients per year. At this time, Apligraf® has not been approved for use in Sweden.

Patient benefit and side effects

The effects of Apligraf® treatment have been studied in a randomized open study of 293 patients. Apligraf® in combination with compression treatment was compared to compression treatment alone. The study showed that the addition of Apligraf® resulted in both a higher percentage of healed wounds and a shorter median time for healing in patients who had large ulcers and/or have had ulcers for a longer period. No significant differences were found between treatment alternatives in patients who had ulcers for periods shorter than 6 months. No signs of immunological reactions or other side effects of transplantation have been reported. As regards other side effects (eg, infection, pain, development of necrosis, and inflammation) no differences were observed in comparison to patients in the control group. However, there is some uncertainty in interpreting the findings since wound size varied in the study and the control groups respectively (larger wounds were less frequent in the group treated with Apligraf®).

Economic aspects

The cost to deliver a treatment using Apligraf® (cost of the product and staff to perform the procedure) for a venous leg ulcer has been estimated at approximately 12 000 Swedish kronor (SEK). Usually, 2 to 4 treatments are required. Three model studies using different alternatives for comparison have presented estimates of cost effectiveness. The results varied, ranging from a cost saving to an additional cost of approximately 85 000 SEK. The studies are based on data from clinical studies with short followup periods. Due to the short followup time in the studies, the strength of the scientific evidence is considered to be poor. The relevance of the findings to Swedish conditions is unclear.

Scientific evidence

Currently, there is poor* documentation concerning the short-term effects of the method. Likewise, there is poor* documentation concerning its cost effectiveness. Further randomized and controlled studies are needed with longer followup times and standardized definitions of hard-to-heal venous ulcers. Also, comparisons must be made with the alternative methods, eg, pinch grafts, to be able to claim that Apligraf® is more cost effective than other methods.

*This assessment by SBU Alert uses a 4-point scale to grade the quality and evidence of the scientific documentation. The grades indicate: (1) good, (2) moderate, (3) poor, or (4) no scientific evidence on the subject.

This summary is based on a report prepared at SBU in collaboration with Assoc. Prof. Mats Bjellerup, Helsingborg Hospital, Helsingborg. It has been reviewed by Gunilla Sjölin-Forsberg, Head of the Pharmacovigilance Unit, Medical Products Agency.

The complete report is available only in Swedish.

SBU Alert is a service provided by SBU in collaboration with the Medical Products Agency, the National Board of Health and Welfare, and the Federation of Swedish County Councils.

References