Cost-effectiveness of Novel Macrophage-Regulating Treatment for Wound Healing in Patients With Diabetic Foot Ulcers From the Taiwan Health Care Sector Perspective

Abstract

ImportanceDiabetic foot ulcers (DFUs) and subsequent amputation incur enormous health and economic burdens to patients, health care systems, and societies. As a novel macrophage-regulating drug, ON101 is a breakthrough treatment for DFUs, which demonstrated significant complete wound healing effects in a phase 3 randomized clinical trial, but its economic value remains unknown.ObjectiveTo assess the cost-effectiveness of an ON101 cream added on to general wound care (GWC; ie, conventional treatments for DFUs, which comprised initial and regular foot examinations, ulcer management, comorbidity control, patient education, and multidisciplinary care) vs GWC alone for DFUs from the Taiwan health care sector perspective.Design, Setting, and ParticipantsThis economic evaluation used a hypothetical cohort of patients with diabetes, with characteristics mirroring those of the participants in the ON101 trial. A Markov state-transition simulation model was constructed to estimate costs and health outcomes associated with the ON101 with GWC and GWC alone strategies over a 5-year time horizon, discounting costs and effectiveness at 3% annually. Costs were in 2021 US dollars. Data were sourced from the ON101 trial and supplemented from published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 1, 2020, to January 31, 2022.ExposuresON101 with GWC vs GWC alone.Main Outcomes and MeasuresDFU-related complications, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio.ResultsPatients in the hypothetical cohort had a mean age of 57 years and an uninfected DFU of 1 to 25 cm2 that was present for 4 or more weeks with a Wagner grade of 1 or 2. Over 5 years, the ON101 with GWC group vs the GWC alone group experienced more healing events, stayed for a longer time in the healing state, and had fewer infected DFUs, gangrene, and amputations (eg, 2787 additional healing events and 2766 fewer infected DFU, 72 fewer amputation, and 7 fewer gangrene events in the ON101 with GWC group vs GWC alone group). The ON101 with GWC strategy vs GWC alone yielded an additional 0.038 QALYs at an incremental cost of $571, resulting in $14 922/QALY gained. Economic results were most sensitive to healing efficacy, drug cost, and health utility of the healing state. Cost-saving results were observed in patient subgroups with poor glycemic control, larger ulcer sizes, longer ulcer durations, and current smoking. The ON101 with GWC strategy was considered cost-effective in 60% to 82% of model iterations against willingness-to-pay thresholds of $32 787/QALY gained to $98 361/QALY gained.Conclusions and RelevanceIn this economic evaluation study using a simulated patient cohort, the ON101 with GWC strategy represented good value compared with GWC alone for patients with DFUs from the Taiwan health care sector perspective and may be prioritized for those with high risks for disease progression of DFUs.

Risk factors for amputation in diabetic foot ulcers: A retrospective analysis

“…Wagner grading is currently the most commonly used DFU grading method, which is widely used in clinical practice due to its simplicity, practicality and inclusion of high‐risk feet for DFU. Previous studies have shown a close correlation between DFU amputation and Wagner grading, with a significantly increased risk of amputation for Wagner 4–5 grade foot ulcers compared to 0–3 grade ulcers 18–20 . In this study, as the Wagner grading increased, the amputation rate also showed an upward trend.…”

“…Previous studies have shown a close correlation between DFU amputation and Wagner grading, with a significantly increased risk of amputation for Wagner 4-5 grade foot ulcers compared to 0-3 grade ulcers. [18][19][20] In this study, as the Wagner grading increased, the amputation rate also showed an upward trend. Through multiple regression analysis, it was found that the Wagner grading was an independent risk factor for DF amputation, which is consistent with previous research results.…”

The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation

“…Previous clinical trials have focused on diverse strategies to treat DFU, including the delivery of topical recombinant growth factors [ 15 , 45 , 46 , 47 , 48 ], platelet-rich plasma [ 49 ], umbilical cord mesenchymal stromal cells (MSC) [ 50 ], macrophage-regulating drugs (NCT01898923) [ 51 ], or enriched hydrogels with sodium alginate and vitamins. The use of mRNA holds significant promise in the exploration of new pharmaceuticals, especially when upregulation of a protein is desired [ 52 ].…”

Macrophage plasticity: signaling pathways, tissue repair, and regeneration

“…The therapeutic potential of macrophages in cell‐based therapies has been demonstrated in various clinical trials and preclinical studies. 522 , 559 , 560 Macrophages have outperformed stem cells in specific target diseases, showcasing their outstanding regenerative capacity. 561 Conditions such as kidney disease, stroke, arterial disease, and cancer have been targeted using macrophage‐based therapies.…”