Comparative Effectiveness of a Bioengineered Living Cellular Construct and Cryopreserved Cadaveric Skin Allograft for the Treatment of Venous Leg Ulcers in a Real-World Setting.

Objective: A variety of advanced biological therapies are available for the treatment of chronic wounds such as venous leg ulcers (VLUs), but real-world comparative effectiveness data that can help guide decisions around treatments are currently lacking. Approach: This analysis was designed to compare the effectiveness of a bioengineered living cellular construct (BLCC) to a cryopreserved cadaveric skin allograft (CCSA) for the treatment of VLUs. Treatment records were collected from a large wound care-specific electronic medical record database on 717 patients (799 VLUs) receiving treatment at 177 wound care centers. Ulcers ≥28 days duration, between ≥1 and < 40 cm2 that closed ≤40% within the 28 days before treatment were included. Results: Patient baseline demographics and wound characteristics were comparable between groups. The median time to wound closure was 52% faster with BLCC compared with CCSA (15 weeks vs. 31 weeks). In addition, the proportion of wounds healed were significantly higher for BLCC by 12 weeks (42% vs. 24%) and 24 weeks (65% vs. 41%) (p = 0.0002). Treatment with BLCC increased the probability of healing by 97% compared with CCSA (hazard ratio = 1.97 [95% confidence interval 1.39-2.79], p = 0.0002). Innovation: This is the first real-world comparative effectiveness analysis to evaluate BLCC and CCSA for the treatment of VLUs. Conclusion: Treatment with a bioengineered cellular technology significantly improved the incidence and speed of wound closure compared with a CCSA.

The Comparative Effectiveness of a Human Fibroblast Dermal Substitute versus a Dehydrated Human Amnion/Chorion Membrane Allograft for the Treatment of Diabetic Foot Ulcers in a Real-world Setting.

BACKGROUND: Impaired wound healing is associated with serious complications in patients with diabetes. Diabetic foot ulcers (DFUs) can lead to costly complications and an increased mortality rate. Standard treatments for DFUs often need to be augmented with adjunctive therapies designed to stimulate healing in recalcitrant wounds. OBJECTIVE: This analysis was conducted to evaluate the comparative effectiveness of a human broblast-derived dermal substitute (HFDS) and a dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of DFUs. MATERIALS AND METHODS: Using a wound care-specic electronic health record database, real-world outcomes from 122 patients with 122 DFUs receiving treatment in 2014 in 72 wound care facilities across the United States were evaluated. Key criteria for entry into the analysis included ulcer size ≥ 1 cm2 to < 25 cm2, ulcer duration ≤ 1 year, and ulcer area reduction ≤ 20% in the 14 days prior to the rst treatment. Key exclusion criteria included lack of follow-up visits and lack of baseline wound measurements. The frequency of wound closure by weeks 12 and 24, median time to wound closure, hazard ratio with 95% con dence interval, and P value were estimated from a Cox model with terms for treatment, baseline wound area, baseline wound duration, baseline wound depth, and wound location. RESULTS: The results show the incidence of wound closure for HFDS compared with dHACM was signicantly improved by weeks 12 (55% vs. 32%) and 24 (76% vs. 50%). The HFDS treatment signi cantly increased the probability of wound closure by 107%, with a median time to closure of 7.4 weeks (38%) less than that of dHACM treatment (P = .02).

Comparative effectiveness of a bioengineered living cellular construct vs. a dehydrated human amniotic membrane allograft for the treatment of diabetic foot ulcers in a real world setting.

We evaluated the comparative effectiveness of a bioengineered living cellular construct (BLCC) and a dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of diabetic foot ulcers (DFUs). Using a wound care-specific electronic medical record database, we assessed real-world outcomes in 218 patients with 226 DFUs receiving treatment in 2014 at 99 wound care centers. The analysis included DFUs ≥1 and <25 cm2 with duration <=1 year and area reduction ≤20% in 14 days prior to treatment (N=163, BLCC; N=63, dHACM). The average baseline areas and durations were 6.0 cm2 and 4.4 months for BLCC and 5.2 cm2 and 4.6 months for dHACM, respectively. Patients treated with dHACM had more applications compared to those treated with BLCC (median 3.0 vs. 2.0) (p=0.003). A Cox model adjusted for key covariates including area and duration found the median time to closure for BLCC was 13.3 weeks compared to 26 weeks for dHACM, and the proportion of wounds healed were significantly higher for BLCC by 12 weeks (48% vs. 28%) and 24 weeks (72% vs. 47%) (p=0.01). Treatment with a bioengineered living cellular technology increased the probability of healing by 97% compared with a dehydrated amniotic membrane (hazard ratio = 1.97 [95% confidence interval 1.17, 3.33], p=0.01).

Economic outcomes among Medicare patients receiving bioengineered cellular technologies for treatment of diabetic foot ulcers.

OBJECTIVE: To assess the real-world medical services utilization and associated costs of Medicare patients with diabetic foot ulcers (DFUs) treated with Apligraf (bioengineered living cellular construct (BLCC)) or Dermagraft (human fibroblast-derived dermal substitute (HFDS)) compared with those receiving conventional care (CC). METHODS: DFU patients were selected from Medicare de-identified administrative claims using ICD-9-CM codes. The analysis followed an 'intent-to-treat' design, with cohorts assigned based on use of (1) BLCC, (2) HFDS, or (3) CC (i.e., ≥1 claim for a DFU-related treatment procedure or podiatrist visit and no evidence of skin substitute use) for treatment of DFU in 2006-2012. Propensity score models were used to separately match BLCC and HFDS patients to CC patients with similar baseline demographics, wound severity, and physician experience measures. Medical resource use, lower-limb amputation rates, and total healthcare costs (2012 USD; from payer perspective) during the 18 months following treatment initiation were compared among the resulting matched samples. RESULTS: Data for 502 matched BLCC-CC patient pairs and 222 matched HFDS-CC patient pairs were analyzed. Increased costs associated with outpatient service utilization relative to matched CC patients were offset by lower amputation rates (-27.6% BLCC, -22.2% HFDS), fewer days hospitalized (-33.3% BLCC, -42.4% HFDS), and fewer emergency department visits (-32.3% BLCC, -25.7% HFDS) among BLCC/HFDS patients. Consequently, BLCC and HFDS patients had per-patient average healthcare costs during the 18-month follow-up period that were lower than their respective matched CC counterparts (-$5253 BLCC, -$6991 HFDS). LIMITATIONS: Findings relied on accuracy of diagnosis and procedure codes contained in the claims data, and did not account for outcomes and costs beyond 18 months after treatment initiation. CONCLUSION: These findings suggest that use of BLCC and HFDS for treatment of DFU may lower overall medical costs through reduced utilization of costly healthcare services.

Comparative effectiveness of a bilayered living cellular construct and a porcine collagen wound dressing in the treatment of venous leg ulcers.

Using data from a national wound-specific electronic medical record (WoundExpert, Net Health, Pittsburgh, PA), we compared the effectiveness of a bilayered living cellular construct (BLCC) and an acellular porcine small intestine submucosa collagen dressing (SIS) for the treatment of venous leg ulcer. Data from 1,489 patients with 1,801 refractory venous leg ulcers (as defined by failure to have >40% reduction in size in the 4 weeks prior to treatment) with surface areas between 1 and 150 cm(2) in size, treated between July 2009 and July 2012 at 158 wound care facilities across the US were analyzed. Patient baseline demographics and wound characteristics were comparable between groups. Kaplan-Meier-derived estimates of wound closure for BLCC (1,451 wounds) was significantly greater (p = 0.01, log-rank test) by weeks 12 (31% vs. 26%), 24 (50% vs. 41%), and 36 (61% vs. 46%), respectively, compared with SIS (350 wounds). BLCC treatment reduced the median time to wound closure by 44%, achieving healing 19 weeks sooner (24 vs. 43 weeks, p = 0.01, log-rank test). Treatment with BLCC increased the probability of healing by 29% compared with porcine SIS dressing (hazard ratio = 1.29 [95% confidence interval 1.06, 1.56], p = 0.01).

Burden of diabetic foot ulcers for medicare and private insurers.

OBJECTIVE: To estimate the annual, per-patient incremental burden of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: DFU patients and non-DFU patients with diabetes (controls) were selected using two de-identified databases: ages 65+ years from a 5% random sample of Medicare beneficiaries (Standard Analytical Files, January 2007-December 2010) and ages 18-64 years from a privately insured population (OptumInsight, January 2007-September 2011). Demographics, comorbidities, resource use, and costs from the payer perspective incurred during the 12 months prior to a DFU episode were identified. DFU patients were matched to controls with similar pre-DFU characteristics using a propensity score methodology. Per-patient incremental clinical outcomes (e.g., amputation and medical resource utilization) and health care costs (2012 U.S. dollars) during the 12-month follow-up period were measured among the matched cohorts. RESULTS: Data for 27,878 matched pairs of Medicare and 4,536 matched pairs of privately insured patients were analyzed. During the 12-month follow-up period, DFU patients had more days hospitalized (+138.2% Medicare, +173.5% private), days requiring home health care (+85.4% Medicare, +230.0% private), emergency department visits (+40.6% Medicare, +109.0% private), and outpatient/physician office visits (+35.1% Medicare, +42.5% private) than matched controls. Among matched patients, 3.8% of Medicare and 5.0% of privately insured DFU patients received lower limb amputations. Increased utilization resulted in DFU patients having $11,710 in incremental annual health care costs for Medicare, and $16,883 for private insurance, compared with matched controls. Privately insured matched DFU patients incurred excess work-loss costs of $3,259. CONCLUSIONS: These findings document that DFU imposes substantial burden on public and private payers, ranging from $9-13 billion in addition to the costs associated with diabetes itself.