Comparison of IFSG to SOC for treatment of venous leg ulcers using real-world data from the USWR with 1:1 matching on 14 wound/patient factors

Background: Venous leg ulcers (VLUs) impose substantial morbidity and Medicare spending, yet many real world ulcers remain refractory to standard of care (SOC). Intact fish skin graft (IFSG) is a biologic tissue graft used for chronic wounds. We evaluated the comparative effectiveness of IFSG versus SOC in routine practice using a specialty wound registry with Real World Evidence design features intended to minimize bias. Methods: We performed a retrospective, target trial emulating, 1:1 propensity score matched comparative effectiveness study within the U.S. Wound Registry (USWR). Matching used 14 prespecified patient and wound level covariates (including mobility as a measure of frailty and number of concomitant wounds). Results: The matched cohort included 129 IFSG treated VLUs and 129 SOC treated VLUs. Baseline balance was excellent by standardized mean differences. Small residual differences favored SOC; IFSG treated wounds were older and trended larger. Healing occurred in 85.3% of IFSG treated wounds (110/129) versus 75.2% of SOC treated wounds (97/129); the absolute difference (+10.1%) was just below statistical significance (p=0.0801). SOC treated VLUs increased in size on average more than IFSG treated VLUs (p=0.0036). Conclusions: In a national wound registry with rigorous cohort construction, aligned index timing, comprehensive covariate control, and structured outcome capture, IFSG demonstrated favorable real world effectiveness versus SOC for VLUs with a trend towards more healed wounds and a statistically significant lower average wound expansion. The high healing rate in the SOC arm is plausibly explained by baseline advantages (shorter duration, smaller area, and never advanced therapy selection) as well as the absence of a set follow up duration that typically extended until healing, a competing event, or administrative end of observation.