Systematic review of cellular and tissue products and Indirect treatment comparison between cellular/acellular and amniotic/non-amniotic allografts in the management of diabetic foot ulcers.

Introduction: Our study aimed to compare the efficacy of cell and tissue products (CTP) dressings in the management of diabetic foot ulcers (DFUs) based on published randomized control trials (RCTs) and conduct an indirect treatment comparison of cellular/acellular CTPs and amniotic/non-amniotic membranes to help decision makers and clinicians with choosing the most effective CTP solution.

Methods: We searched PubMed, EMBASE, Cochrane and other databases to identify relevant randomized controlled trials. To maintain consistency of analysis, only trials which included subjects clinically diagnosed with a DFU ≥ 2cm2, randomized against standard of care arm, had a screening period, and reported a 12-week closure outcome were included for statistical analysis. We performed meta-analysis of all CTPs. An indirect treatment comparison (ITC) of cellular/acellular and amniotic/non-amniotic CTPs was also performed due to the paucity of direct head-to-head evidence.

Results: The use of CTPs was associated with a statistically significant increase in wound closure rates when compared to standard of care with a Risk Ratio (RR) 1.77 [1.61, 1.95] p< 0.00001. Cellular and acellular subgroups showed a statistically significant increase in wound closure rates compared to standard of care (81% and 77% respectively). Amniotic and non-amniotic membranes also showed a statistically significant increase in wound closure compared to standard of care (86% and 76% respectively). The indirect treatment comparison between cellular and acellular CTPs as well as amniotic and non-amniotic membranes however failed to reach statistical significance, with cellular and amniotic membranes being slightly more effective than acellular and non-amniotic allografts respectively.

Discussion: Review of RCTs confirms that all CTPs used as adjunct to standard of care results in statistically superior wound closure outcome in DFUs, when compared to standard of care alone. While cellular CTPs and amniotic allografts tend to have a better closure outcome than acellular and non-amniotic allografts respectively, enough evidence is lacking at this point to determine a statistical difference and hence decision makers should consider published head-head comparative studies as well as cost-effectiveness evidence as they decide on which CTP to use in practice.