Cost-effectiveness of Recurrent Dupuytren Contracture Treatment

Key Points Question What is the most cost-effective treatment regimen for recurrent Dupuytren contracture based on disease characteristics? Findings In this economic evaluation, limited fasciectomy was a cost-effective treatment for recurrent severe (ie, >45°) Dupuytren contracture at the metacarpophalangeal joint compared with percutaneous needle aponeurotomy. In low-severity metacarpophalangeal joint and proximal interphalangeal joint contractures, percutaneous needle aponeurotomy was the only cost-effective intervention. Meaning In this study, limited fasciectomy was cost-effective for treating recurrent, severe metacarpophalangeal joint contractures, but percutaneous needle aponeurotomy was the only cost-effective treatment for recurrent low-severity metacarpophalangeal joint contractures and recurrent proximal interphalangeal joint contractures.


Introduction
Dupuytren contracture is a late manifestation of Dupuytren disease, a chronic fibroproliferative disorder of the palmar fascia that preferentially affects the ring and small fingers. 1,2 Its prevalence is between 1% and 32% in North American and European populations. 3,4 In England, the yearly national estimated treatment cost for Dupuytren contracture is £41 576 141 ($52 047 092). 5 Dupuytren contracture is commonly managed with limited fasciectomy (LF), a surgical procedure that removes diseased connective tissue. 6 However, less invasive alternatives, such as enzymatic release with collagenase clostridium histolyticum (CCH) injection and manual division of cords using percutaneous needle aponeurotomy (PNA), have both demonstrated efficacy. 7 CCH and PNA are associated with faster recovery time and consume fewer resources than LF. [8][9][10] However, the likelihood that the contracture will recur following treatment may be greater for PNA and CCH. 7,11 In addition, some studies show that PNA and CCH are less effective for treating proximal interphalangeal (PIP) joint contractures compared with LF 11,12 and that severe contractures are more amenable to treatment with LF. 10,13,14 Balancing these trade-offs can make treatment selection challenging, especially when no formal treatment guidelines exist. Consequently, both nonsurgical and surgical treatments are applied in various combinations to the same joint when Dupuytren contracture recurs. 15,16 Furthermore, as treatment costs for LF, PNA, and CCH differ substantially, 8 identifying the most cost-effective treatment regimen has the potential to considerably reduce health care expenditure. Because recurrence and treatment success vary with contracture severity and affected joint type, 17-20 it is likely that these disease characteristics are associated with the cost-effectiveness of Dupuytren contracture treatments. Prior cost-effectiveness studies on Dupuytren contracture treatment generated conflicting conclusions. 8,13,21,22 The National Health Service in the United Kingdom suggested that LF is the most cost-effective intervention, 13 yet other studies found the opposite. 8,21 To our knowledge, no study has incorporated both contracture severity and affected joint type when modeling the cost-effectiveness of treating recurrent Dupuytren contracture.
Furthermore, previous studies used cohort models, such as decision trees and Markov models, that limited their ability to incorporate patient-level parameters. A microsimulation model presents an opportunity to integrate these patient-level characteristics to more accurately project treatment costs and health effects gained for different Dupuytren contracture phenotypes. 23 Unlike prior studies, a microsimulation can model individualized disease outcomes and probabilities that depend on cumulative events in a patient's history, such as contracture recurrence.
The economic burden associated with treating Dupuytren contracture increased by almost 50% between 1998 and 2011 and is projected to increase as the population ages. 22 The aim of this study was to identify cost-effective treatment regimens for recurrent Dupuytren contracture based on patient-level characteristics that have known associations with treatment outcome and recurrence. To accomplish this, we conducted a microsimulation economic analysis incorporating patients' contracture severity, affected joint type, and number of joints affected.

Methods
The methods and presentation of study findings adhered to the Consolidated Health Economic

Model Design
We compared the cost-effectiveness of 3 interventions (CCH, PNA, and LF) using state-transition microsimulation modeling with a lifetime horizon. The model incorporated both societal and healthsector perspectives in the context of health care in the United States. The base case scenario was a patient aged 60 years with low-severity MCP joint contracture. Contractures of less than 45°from full finger extension were defined as low severity and those greater than 45°as high severity. Scenarios considered in the model were high-severity MCP joint, low-severity PIP joint, and high-severity PIP joint contractures.
The overall model structure included the 3 following health states: (1) symptom-free state (ie, treatment success), (2) symptomatic state (ie, recurrence or treatment failure) and (3)

Cost and Health Outcomes
Procedure cost, anesthesia cost, facility fee, hand therapy, collagenase medication, additional cost from complications, and collagenase injection and manipulation clinic visits were considered direct costs. Physician fees were derived from the 2019 National Physician Fee schedule using Current Procedural Terminology (CPT) codes (Table 1). 45 Facility fees were determined from the Medicare Outpatient Prospective Payer System, and collagenase costs were gleaned from literature review. 8 Indirect costs, such as wages lost from time off work after each intervention, were based on 2018 US median income. 49 Only complications associated with substantial cost or long-term impairment in quality of life were included. Rates of complication were derived from the literature. 10,12,17,20,25,36,39,[41][42][43][44]46,47 The frequency and type of hand therapy associated with each treatment were provided by hand therapists at Michigan Medicine, and costs were calculated using Medicare fee schedules.
Health utilities were calculated using a previously described discrete choice experiment (Table 1). 48 A weighted mean utility based on Dupuytren disease prevalence of each finger was calculated for the base case single joint analysis. 27 For the 2-finger analysis, utilities were calculated for ring and small finger Dupuytren contractures.

Model Assumptions and Validation
The model assumed that the probability of immediate treatment failure was the inverse of the success rate for each intervention. Utilities lost from complications were not considered because most complications were relatively rare and short-term. In addition, the discrete choice experiment formula used does not consider complications when calculating utilities. In alignment with general practice, we assumed that PNA and CCH were performed in clinic, whereas LF was performed in the operating room under general anesthesia. Because of the 1-year cycle length, patients who recurred or had treatment failure accumulated a discounted utility for an entire year. The symptomatic state utility was identical regardless of treatment. Furthermore, because of limited outcome data for treating recurrent contractures, we assumed that the probability of success and recurrence for each treatment type would remain constant whether used as the initial treatment vs treatment for

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Cost-effectiveness of Recurrent Dupuytren Contracture Treatment

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Cost-effectiveness of Recurrent Dupuytren Contracture Treatment

Statistical Analysis
The primary outcome measure was the incremental cost-effectiveness ratio (ICER) among the 27 unique treatment regimens. The ICER was calculated by dividing the difference in total cost between 2 treatment regimens by the corresponding difference in quality-adjusted life-years (QALY) gained.
The net monetary benefit (NMB) for each treatment regimen was estimated using the formula 50 NMB = λ × Δ e -Δ c , in which λ is the willingness-to-pay threshold, e is effectiveness, and c is cost.
One-way sensitivity analysis varying all model parameters was conducted to identify the most influential factors in determining cost-effectiveness (

Results
In a simulated cohort of 10 000 patients with high-severity MCP joint contractures, the mean (SD) time to first recurrence was 26 (28.9) months after PNA and 29 (31.7) months after CCH. These were comparable to published recurrence times of 19 to 33 months for PNA and 24 months for CCH. 10 . Probabilistic sensitivity analysis revealed that, at a willingness-to-pay threshold of $100 000 per QALY, PNA for all 3 treatments had a 44%, 15%, 41%, and 52% chance of being the most cost-effective intervention in low-severity MCP joint contracture, high-severity MCP joint contracture, low-severity PIP joint contracture, and high-severity PIP joint contracture, respectively (Figure 2 and Figure 3). As the willingness-to-pay threshold increased, it became less likely that PNA for all 3 treatments would be the most cost-effective intervention, although a better alternative strategy was unclear. A separate analysis was conducted to simulate cost-effectiveness when PNA was performed in the operating room (data not shown). Despite the added cost, having PNA for all 3 treatments continued to be the only cost-effective treatment regimen for low-severity MCP, low-severity PIP, and high-severity PIP joint contractures. In high-severity MCP joint contractures, any treatment regimen that involved LF at least once had an ICER less than $100 000 per QALY.
From a health-sector perspective, similar to societal perspective results, treatment regimens with PNA and LF were cost-effective for high-severity MCP joint contractures, whereas repeated PNA was the only cost-effective strategy for the remaining joint and severity types (eTable 2 in the

Discussion
This study suggests that the most cost-effective treatment regimen for recurrent Dupuytren contracture is associated with joint type, contracture severity, and number of fingers affected. In single-digit high-severity MCP joint contractures, PNA for the initial treatment followed by LF to manage recurrence was a cost-effective treatment regimen. In the remaining joint and severity types, for patients with 2-finger Dupuytren contracture whose quality of life is severely impacted, LF may be cost-effective, as seen in our 2-finger disease 1-way sensitivity analysis. Furthermore, we believe this interpretation can be cautiously extrapolated to patients with multiple fingers (ie, >2) affected, making LF a cost-effective treatment for those patients.

Limitations
The findings of this study should be interpreted within the context of some limitations. Because no randomized clinical trial with a direct comparison of all 3 treatments exists, the transition probabilities were derived from studies that compared 2 treatments or a single treatment to a placebo. Both prospective and retrospective studies were included to gather sufficient data to calculate transition probabilities based on both joint type and contracture severity. This can introduce heterogeneity into the model because the treatment arms of each study will likely have patients with different characteristics. To address these uncertainties and heterogeneity, we conducted both deterministic and probabilistic sensitivity analyses, varying the model parameters over feasible ranges. In addition, there may be other patient-level risk factors that affect treatment success and recurrence, such as Garrod pads, bilateral involvement, age of onset, and family history. 55 These factors were ultimately excluded from the model owing to insufficient high-quality evidence. Assessing recurrence of Dupuytren contracture can be challenging because of similarities

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Cost-effectiveness of Recurrent Dupuytren Contracture Treatment in presentation with scar contractures, especially in recurrences after LF. To maximize the inclusion of only true Dupuytren contracture recurrence rates in the literature, we adopted strict inclusion criteria for recurrences as contractures greater than 20°.
Our findings should not be generalized to countries outside of the United States because of different health care costs and mortality rates. This study benefits from a microsimulation modeling technique that better reproduces the natural process of Dupuytren disease through stochastic uncertainty. In addition, this modeling strategy accommodates complexity in patient-level factors, such as joint type, contracture severity, and number of fingers affected, which affect costeffectiveness. Furthermore, numerous potential treatment regimens for recurrent Dupuytren contracture were simulated with 27 treatment permutations.

Conclusions
In this study, LF and PNA were cost-effective treatments for managing recurrent, high-severity Dupuytren contracture of the MCP joint. For patients with recurrent single-finger, low-severity MCP joint contracture or recurrent PIP joint contractures of any severity, PNA was the only cost-effective strategy. In Dupuytren disease involving 2 low-severity MCP or PIP joint contractures, a treatment combination of PNA and LF may be cost-effective compared with repeated PNA in patients with markedly diminished quality of life. CCH was not a cost-effective treatment for Dupuytren contracture of any joint or severity.