Key PointsQuestion
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.
Importance
Owing to its tendency to recur, Dupuytren contracture often requires multiple treatments, which places additional economic burden on health care. The likelihood of contracture recurrence varies not only with treatment but also with disease characteristics, such as contracture severity and location, but prior cost-effectiveness analyses of Dupuytren contracture treatments have not considered these patient-specific disease characteristics.
Objective
To identify the most cost-effective treatment regimen for patients with recurrent Dupuytren contracture.
Design, Setting, and Participants
This economic evaluation was conducted with state-transition microsimulation modeling using data from published studies and Medicare. A simulated cohort of 10 000 individuals with Dupuytren contracture was created. Patients could transition yearly between the following health states: symptom-free, symptomatic, and death. Available treatments were collagenase clostridium histolyticum injection, percutaneous needle aponeurotomy (PNA), and limited fasciectomy (LF); individuals randomly chose any treatment when symptomatic. Patients were limited to 3 rounds of treatment for a contracture affecting 1 joint, totaling 27 unique combinations. If the contracture recurred after 3 treatments, patients lived with the disease for the remainder of life.
Exposures
PNA, collagenase clostridium histolyticum injection, or LF.
Main Outcomes and Measures
Quality-adjusted life-years (QALYs), total costs (in US dollars), and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per quality-adjusted life-year was used to assess cost-effectiveness.
Results
For the base case scenario of a patient aged 60 years with recurrent, low-severity metacarpophalangeal (MCP) joint contracture, repeated PNA treatment was the only cost-effective treatment (2 PNA treatments followed by LF vs 3 PNA treatments, ICER [Monte Carlo SE]: $212 647/QALY [$36 000/QALY]). For recurrent high-severity MCP joint contractures, treatment regimens composed of PNA and LF were cost-effective (ICER [Monte Carlo SE], $93 932/QALY [$16 500/QALY]). LF was cost-effective for high-severity MCP joint contracture (ICER [Monte Carlo SE], $98 624/QALY [$26 233/QALY]). For recurrent proximal interphalangeal (PIP) joint contractures, PNA was the only cost-effective treatment, regardless of severity (eg, 2 PNA treatments followed by LF vs 3 PNA treatments for low-severity PIP joint contracture, ICER [Monte Carlo SE]: $263 726/QALY [$29 000/QALY]). Any combination with collagenase clostridium histolyticum injection compared with 3 PNA treatments had an ICER greater than $100 000 per QALY. Probabilistic sensitivity analysis estimated a 44%, 15%, 41%, and 52% chance of a regimen consisting of only PNA being cost-effective in low-severity MCP, high-severity MCP, low-severity PIP, and high-severity PIP joint contractures, respectively.
Conclusions and Relevance
The results of this study suggest that LF is a cost-effective intervention for recurrent high-severity MCP joint contractures. For recurrent low-severity MCP joint contractures and PIP joint contractures of all severity levels, PNA was the only cost-effective intervention. Collagenase clostridium histolyticum injections were not a cost-effective intervention for recurrent Dupuytren contracture and should not be preferred over PNA or LF.
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.8-10 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 LF11,12 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.
The methods and presentation of study findings adhered to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline. According to the University of Michigan institutional review board, this study fell under the University of Michigan’s policy for research using publicly available data sets. Under this policy and in accordance with federal regulations for human subjects research (45 CFR Part 46), institutional review board approval was not required because the data cannot be tracked to a human participant.
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 health-sector 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) death from other causes (Figure 1). Every patient entered the model with diagnosed Dupuytren contracture desiring intervention. The cycle length for the microsimulation was 1 year with a lifetime horizon, indicating that all simulated patients could transition between health states once per year until death. Likewise, this cycle length permits patients in the symptomatic state to receive 1 treatment per year. At the start of the simulation, patients underwent CCH, PNA, or LF as their first treatment while in the symptomatic state. Then, depending on the probability of a treatment’s success relative to patient characteristics, the patient transitioned to the symptom-free state if the treatment succeeded or remained in the symptomatic state if the treatment failed. Patients who achieved a symptom-free state could revert back to the symptomatic state each year, depending on the probability of recurrence, which represented the risk of developing recurrent contracture. The probability for a contracture to recur after treatment depended on the chosen treatment and contracture characteristics, similar to the probability of treatment success. Patients could attempt a maximum of 3 treatments for a single contracture, but if the contracture recurred after the third treatment, the patient lived with the disease until death, accruing reduced utilities each year. With a maximum of 3 treatments chosen at random, 27 unique treatment regimens comprised of CCH, PNA, and LF were possible.
Contingent on age-dependent mortality rates,24 the patient could transition to an all-absorptive death state (ie, the patient cannot come out of the death state) where no cost or utility accrued. For each joint type and severity, 10 000 unique simulated patients living with recurrent Dupuytren contracture were generated. Cost and health outcomes were discounted by 3% each year. Patients accrued cost and decreased utilities associated with treatments and for time spent in the symptomatic state.
Based on published data, we calculated transition probabilities for treatment success and recurrence for each intervention and associated joint type and contracture severity. The studies included for the calculation of transition parameters were published between 2002 and 2018, with a mean follow-up time of 1.6 years (range: 1 month to 2 years).9-11,14,17,20,25-39 In accordance with previous randomized clinical trials, we included studies that defined treatment success as less than 5° of residual contracture at 30-day follow-up. Recurrence was defined as return of a contracture greater than 20°.17,26,28,40 First, a baseline weighted mean probability of success and recurrence for each intervention was calculated. Then, these probabilities were adjusted by the relative risk of success and recurrence contingent on the affected joint type and contracture severity (Table 1).2,4,8,9,11-14,17,20,21,24,25,28-30,32-49
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.10,12,17,20,25,36,39,41-44,46,47 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 recurrence. Lastly, the model assumed that patients sought treatment for 3 episodes of recurrent Dupuytren contracture, although in reality some patients may defer treatment much earlier.
Several hand surgeons with expertise in Dupuytren contracture confirmed the face validity of the model by evaluating the model structure, data sources, assumptions, and results. The accuracy of the code was validated by code breaks, independent line-by-line code review by 2 of us (A.P.Y. and D.W.H.), and sensitivity analyses. External validity was evaluated by comparing the model’s estimation of mean recurrence time to reported literature times.
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 formula50 NMB = λ × Δe – Δc, 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 (Table 1). A willingness-to-pay threshold of $100 000 per QALY was used as the cost-effectiveness threshold.51,52 Probabilistic sensitivity analysis simulating uncertainty in all parameters simultaneously was conducted to generate cost-effectiveness acceptability curves using a Monte Carlo simulation modeling 10 000 patients with randomly selected model parameters within a clinically feasible distribution. Uncertain intervals were represented by standard deviation or Monte Carlo Standard Error (MCSE). The modeling and analysis were conducted with R Studio version 1.2.5033 (R Project for Statistical Computing) adapting a previously published microsimulation script.53 Statistical significance was set at a 2-tailed P < .05.
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.10,54 PIP joint contractures had shorter mean (SD) time to first recurrence than MCP joint contractures (PNA: 5.0 [2.5] years vs 7.5 [4.4] years; P < .001; LF: 7.4 [4.7] years vs 10.7 [5.8] years; P < .001).
PNA for all 3 treatments was the least expensive strategy (eg, mean [SD] total cost for low-severity MCP joint contracture: $3339 [$544]), whereas LF for all 3 treatments was the most expensive (eg, mean [SD] total cost for low-severity MCP joint contracture: $25 419 [$6785]). Mean (SD) lifetime accumulated QALYs were slightly higher for having all 3 treatments be LF compared with PNA (eg, low-severity MCP joint contracture: 15.17 [4.98] vs 15.08 [4.95]), whereas, for every Dupuytren contracture phenotype, the cost of all 3 treatments being LF was more than 8-fold higher than PNA (Table 2; eFigure 1 in the Supplement). Having PNA for all 3 treatments was the only cost-effective regimen for every joint type and severity level, except for high-severity MCP joint contracture, assuming a decision-maker is not willing to pay more than $200 000 per QALY gained (Table 2). In high-severity MCP joint contractures, starting with PNA the first 2 times and moving to LF after the second recurrence had an ICER of $93 932 (MCSE, $16 500) per QALY. Having LF for all 3 treatments among patients with high-severity MCP joint contracture had an ICER of $98 624 (MCSE, $26 333) per QALY (Table 2).
One-way sensitivity analysis revealed that the utility during symptomatic state was the most important parameter influencing cost-effectiveness in every joint type and severity, except high-severity PIP joint contractures (eTable 1 in the Supplement). When the symptomatic state utility was 5% lower than the base case utility, treatment combinations of PNA and LF became cost-effective for low-severity MCP and PIP joint contractures. PNA for all 3 episodes remained the most cost-effective treatment combination for high-severity PIP joint contractures irrespective of variations in any single parameter. LF was favored for high-severity MCP joint contracture with the following characteristics: younger patients, lower wage losses, lower facility fee, lower PNA success rate, and higher LF success rate. The contrary of these characteristics favored PNA (eTable 1 in the Supplement). 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 Supplement). When the model simulated 2 fingers (ring and small fingers) affected by Dupuytren contracture simultaneously, any treatment combination of LF and PNA remained cost-effective in high-severity MCP joint contractures (eTable 3 in the Supplement). Two rounds of PNA followed by LF had lower ICERs for patients with 2-finger involvement vs 1-finger involvement (ICER [MCSE] for low-severity MCP: $120 999/QALY [$36 000/QALY] vs $212 647/QALY [$36 000/QALY]; low-severity PIP: $127 131/QALY [$14 500/QALY] vs $263 726/QALY [$29 000/QALY]) (Table 2; eTable 3 in the Supplement). Probabilistic sensitivity analysis revealed a 34%, 10%, 20%, and 40% chance of having all 3 treatments be PNA being the most cost-effective treatment combination for patients with 2-finger low-severity MCP, high-severity MCP, low-severity PIP, and high-severity PIP contractures, respectively (eFigure 2 and eFigure 3 in the Supplement).
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, PNA was the only cost-effective treatment for recurrent contractures. Similar overall findings were observed in 2-finger disease; however, if the patient's quality of life is severely affected by Dupuytren contracture, LF may become a cost-effective treatment even for low-severity MCP and PIP joint contractures. Treatment regimens involving CCH were not found to be cost-effective in any scenario.
Few cost-effectiveness analyses have rigorously analyzed Dupuytren contracture treatments. A 2011 study from the United States8 concluded that LF and CCH are not cost-effective compared with PNA using a decision-tree model. However, this study did not account for recurrence, lacked probabilistic sensitivity analysis, and may have overinflated utilities. Nevertheless, our results support this study’s findings that the current price of CCH in the United States does not make it a cost-effective agent. Similarly, our microsimulation also found that PNA was the most cost-effective method in low-severity MCP joint contractures. On the contrary, a UK study concluded that LF is the most cost-effective treatment because of greater QALY gain and lower recurrence rate compared with PNA or CCH.13 However, this should be interpreted with caution given that the cost of LF in the UK ($2700) is considerably cheaper than in the US ($5411).13 Furthermore, this study did not consider affected joint type and limited the third-line treatment to LF. Nonetheless, the similarity of their findings to our own adds face validity to our microsimulation, demonstrating that despite the higher cost of LF, patients accrued the most QALYs compared with PNA and CCH.
Our review of the literature found that the risk-adjusted probabilities of treatment success for high-severity PIP joint contractures were approximately 13% for CCH, 21% for PNA, and 25% for LF. Overall, treatment success was lower for PIP joints than MCP joints in every treatment. Because PNA is the least expensive intervention and no treatment is particularly effective for PIP joints, this may explain why repeated PNA was the only cost-effective treatment regimen for single PIP joint Dupuytren contracture in our model. Estimated utilities after non–life-threatening conditions such as Dupuytren contracture are generally high, even when disease-specific quantitative techniques, such as discrete choice experiments, are implemented.48 When multiple digits are involved, the health utility correspondingly decreases. However, the treatment costs for LF increase by a relatively nominal amount owing to longer operative time and slightly higher professional fees. Consequently, 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.
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 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 cost-effectiveness. Furthermore, numerous potential treatment regimens for recurrent Dupuytren contracture were simulated with 27 treatment permutations.
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.
Accepted for Publication: July 29, 2020.
Published: October 8, 2020. doi:10.1001/jamanetworkopen.2020.19861
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Yoon AP et al. JAMA Network Open.
Corresponding Author: Kevin C. Chung, MD, MS, Section of Plastic Surgery, Department of Surgery, University of Michigan Medical School, 1500 E Medical Center Dr, 2130 Taubman Center, SPC 5340, Ann Arbor, MI 48109-5340 (kecchung@med.umich.edu).
Author Contributions: Drs Yoon and Chung had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Yoon, Kane, Hutton.
Drafting of the manuscript: Yoon, Kane, Chung.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Yoon, Hutton.
Obtained funding: Chung.
Administrative, technical, or material support: Chung.
Supervision: Yoon, Hutton, Chung.
Conflict of Interest Disclosures: Dr Chung reported receiving grants from the National Institutes of Health, receiving book royalties from Wolters Kluwer and Elsevier, and consulting for Axogen outside the submitted work. No other disclosures were reported.
Additional Contributions: The authors would like to thank Jeanne Riggs, CHT (Michigan Medicine), for her contributions to ascertaining hand therapy protocols and costs. Her written permission was obtained to be included in the acknowledgment, and she was not compensated for her time.
3.Dibenedetti
DB, Nguyen
D, Zografos
L, Ziemiecki
R, Zhou
X. Prevalence, incidence, and treatments of Dupuytren’s disease in the United States: results from a population-based study.
Hand (N Y). 2011;6(2):149-158. doi:
10.1007/s11552-010-9306-4PubMedGoogle ScholarCrossref 10.van Rijssen
AL, Gerbrandy
FS, Ter Linden
H, Klip
H, Werker
PM. A comparison of the direct outcomes of percutaneous needle fasciotomy and limited fasciectomy for Dupuytren’s disease: a 6-week follow-up study.
J Hand Surg Am. 2006;31(5):717-725. doi:
10.1016/j.jhsa.2006.02.021PubMedGoogle ScholarCrossref 11.van Rijssen
AL, ter Linden
H, Werker
PM. Five-year results of a randomized clinical trial on treatment in Dupuytren’s disease: percutaneous needle fasciotomy versus limited fasciectomy.
Plast Reconstr Surg. 2012;129(2):469-477. doi:
10.1097/PRS.0b013e31823aea95PubMedGoogle ScholarCrossref 12.Zhou
C, Hovius
SE, Slijper
HP,
et al. Collagenase clostridium histolyticum versus limited fasciectomy for Dupuytren’s contracture: outcomes from a multicenter propensity score matched study.
Plast Reconstr Surg. 2015;136(1):87-97. doi:
10.1097/PRS.0000000000001320PubMedGoogle ScholarCrossref 13.Brazzelli
M, Cruickshank
M, Tassie
E,
et al. Collagenase clostridium histolyticum for the treatment of Dupuytren’s contracture: systematic review and economic evaluation.
Health Technol Assess. 2015;19(90):1-202. doi:
10.3310/hta19900PubMedGoogle ScholarCrossref 14.Muppavarapu
RC, Waters
MJ, Leibman
MI, Belsky
MR, Ruchelsman
DE. Clinical outcomes following collagenase injections compared to fasciectomy in the treatment of Dupuytren’s contracture.
Hand (N Y). 2015;10(2):260-265. doi:
10.1007/s11552-014-9704-0PubMedGoogle ScholarCrossref 15.Bear
BJ, Peimer
CA, Kaplan
FTD, Kaufman
GJ, Tursi
JP, Smith
T. Treatment of recurrent Dupuytren contracture in joints previously effectively treated with collagenase clostridium histolyticum.
J Hand Surg Am. 2017;42(5):391.e1-391.e8. doi:
10.1016/j.jhsa.2017.02.010PubMedGoogle ScholarCrossref 16.Nordenskjöld
J, Lauritzson
A, Waldén
M, Kopylov
P, Atroshi
I. Surgical fasciectomy versus collagenase injection in treating recurrent Dupuytren disease: study protocol of a randomised controlled trial.
BMJ Open. 2019;9(2):e024424. doi:
10.1136/bmjopen-2018-024424PubMedGoogle Scholar 18.Crean
SM, Gerber
RA, Le Graverand
MP, Boyd
DM, Cappelleri
JC. The efficacy and safety of fasciectomy and fasciotomy for Dupuytren’s contracture in European patients: a structured review of published studies.
J Hand Surg Eur Vol. 2011;36(5):396-407. doi:
10.1177/1753193410397971PubMedGoogle ScholarCrossref 20.Peimer
CA, Blazar
P, Coleman
S, Kaplan
FT, Smith
T, Lindau
T. Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-year data.
J Hand Surg Am. 2015;40(8):1597-1605. doi:
10.1016/j.jhsa.2015.04.036PubMedGoogle ScholarCrossref 23.Laramée
P, Millier
A, Brodtkorb
TH,
et al. A comparison of Markov and discrete-time microsimulation approaches: simulating the avoidance of alcohol-attributable harmful events from reduction of alcohol consumption through treatment of alcohol dependence.
Clin Drug Investig. 2016;36(11):945-956. doi:
10.1007/s40261-016-0442-7PubMedGoogle Scholar 25.Alberton
F, Corain
M, Garofano
A,
et al. Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: report of 40 cases.
Musculoskelet Surg. 2014;98(3):225-232. doi:
10.1007/s12306-013-0304-xPubMedGoogle Scholar 28.Hurst
LC, Badalamente
MA, Hentz
VR,
et al; CORD I Study Group. Injectable collagenase clostridium histolyticum for Dupuytren’s contracture.
N Engl J Med. 2009;361(10):968-979. doi:
10.1056/NEJMoa0810866PubMedGoogle Scholar 29.Strömberg
J, Ibsen Sörensen
A, Fridén
J. Percutaneous needle fasciotomy versus collagenase treatment for Dupuytren contracture: a randomized controlled trial with a two-year follow-up.
J Bone Joint Surg Am. 2018;100(13):1079-1086. doi:
10.2106/JBJS.17.01128PubMedGoogle Scholar 30.Witthaut
J, Jones
G, Skrepnik
N, Kushner
H, Houston
A, Lindau
TR. Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies.
J Hand Surg Am. 2013;38(1):2-11. doi:
10.1016/j.jhsa.2012.10.008PubMedGoogle Scholar 31.Simón-Pérez
C, Alía-Ortega
J, García-Medrano
B,
et al. Factors influencing recurrence and progression of Dupuytren’s disease treated by collagenase clostridium histolitycum.
Int Orthop. 2018;42(4):859-866. doi:
10.1007/s00264-017-3690-0PubMedGoogle Scholar 33.Selles
RW, Zhou
C, Kan
HJ, Wouters
RM, van Nieuwenhoven
CA, Hovius
SER. Percutaneous aponeurotomy and lipofilling versus limited fasciectomy for Dupuytren’s contracture: 5-year results from a randomized clinical trial.
Plast Reconstr Surg. 2018;142(6):1523-1531. doi:
10.1097/PRS.0000000000004982PubMedGoogle Scholar 36.Gaston
RG, Larsen
SE, Pess
GM,
et al. The efficacy and safety of concurrent collagenase clostridium histolyticum injections for 2 Dupuytren contractures in the same hand: a prospective, multicenter study.
J Hand Surg Am. 2015;40(10):1963-1971. doi:
10.1016/j.jhsa.2015.06.099PubMedGoogle Scholar 37.Hansen
KL, Werlinrud
JC, Larsen
S, Ipsen
T, Lauritsen
J. Difference in success treating proximal interphalangeal and metacarpophalangeal joints with collagenase: results of 208 treatments.
Plast Reconstr Surg Glob Open. 2017;5(4):e1275. doi:
10.1097/GOX.0000000000001275PubMedGoogle Scholar 38.Gilpin
D, Coleman
S, Hall
S, Houston
A, Karrasch
J, Jones
N. Injectable collagenase clostridium histolyticum: a new nonsurgical treatment for Dupuytren’s disease.
J Hand Surg Am. 2010;35(12):2027-38.e1. doi:
10.1016/j.jhsa.2010.08.007PubMedGoogle Scholar 39.McMahon
HA, Bachoura
A, Jacoby
SM, Zelouf
DS, Culp
RW, Osterman
AL. Examining the efficacy and maintenance of contracture correction after collagenase clostridium histolyticum treatment for Dupuytren’s disease.
Hand (N Y). 2013;8(3):261-266. doi:
10.1007/s11552-013-9524-7PubMedGoogle Scholar 40.Mickelson
DT, Noland
SS, Watt
AJ, Kollitz
KM, Vedder
NB, Huang
JI. Prospective randomized controlled trial comparing 1- versus 7-day manipulation following collagenase injection for Dupuytren contracture.
J Hand Surg Am. 2014;39(10):1933-1941.e1. doi:
10.1016/j.jhsa.2014.07.010PubMedGoogle Scholar 41.Badalamente
MA, Hurst
LC, Benhaim
P, Cohen
BM. Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in Dupuytren contracture: combined analysis of 4 phase 3 clinical trials.
J Hand Surg Am. 2015;40(5):975-983. doi:
10.1016/j.jhsa.2015.02.018PubMedGoogle Scholar 42.Bainbridge
C, Gerber
RA, Szczypa
PP,
et al. Efficacy of collagenase in patients who did and did not have previous hand surgery for Dupuytren’s contracture.
J Plast Surg Hand Surg. 2012;46(3-4):177-183. doi:
10.3109/2000656X.2012.683795PubMedGoogle Scholar 43.Coleman
S, Gilpin
D, Kaplan
FT,
et al. Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple Dupuytren contractures.
J Hand Surg Am. 2014;39(1):57-64. doi:
10.1016/j.jhsa.2013.10.002PubMedGoogle Scholar 46.Bainbridge
C, Dahlin
LB, Szczypa
PP, Cappelleri
JC, Guérin
D, Gerber
RA. Current trends in the surgical management of Dupuytren’s disease in Europe: an analysis of patient charts.
Eur Orthop Traumatol. 2012;3(1):31-41. doi:
10.1007/s12570-012-0092-zPubMedGoogle Scholar 47.Herrera
FA, Mitchell
S, Elzik
M, Roostaeian
J, Benhaim
P. Modified percutaneous needle aponeurotomy for the treatment of Dupuytren’s contracture: early results and complications.
Hand (N Y). 2015;10(3):433-437. doi:
10.1007/s11552-015-9740-4PubMedGoogle Scholar 53.Krijkamp
EM, Alarid-Escudero
F, Enns
EA, Jalal
HJ, Hunink
MGM, Pechlivanoglou
P. Microsimulation modeling for health decision sciences using R: a tutorial.
Med Decis Making. 2018;38(3):400-422. doi:
10.1177/0272989X18754513PubMedGoogle Scholar 54.Scherman
P, Jenmalm
P, Dahlin
LB. Three-year recurrence of Dupuytren’s contracture after needle fasciotomy and collagenase injection: a two-centre randomized controlled trial.
J Hand Surg Eur Vol. 2018;43(8):836-840. doi:
10.1177/1753193418786947PubMedGoogle Scholar