James P. Tursi, MD

Dupuytren’s contracture (DC) is an inherited autosomal dominant disorder that results in abnormal collagen deposition in the hand, and primarily involves the metacarpophalangeal and proximal interphalangeal joints.

Initially, the thickening is painless, but nodules develop in the palm as collagen deposits accumulate. Gradual disease progression leads to cord formation from the palm of the hand across the joint(s) in the finger and can cause the fingers to bend into the palm, resulting in a contracture.

 A study using a Web-based survey design in the United States estimated a prevalence of DC from 1% to 7.3%, depending on the stringency of the disease definition.

The disease is more common among Caucasians of northern European descent than among other groups,

and comorbidities including diabetes, epilepsy,

Garrod’s knuckle pads, Ledderhose disease, and Peyronie’s disease.

For severe and progressive cases, treatments for DC include surgery, which has been the standard treatment for managing DC,

enzyme injections, and needling technique.

 Fasciectomy, the most commonly used surgical technique,

 and collagenase clostridium histolyticum (CCH; brand name Xiaflex) remain the mainstay treatments in the United States. CCH was approved in the United States in 2010 for the treatment of adult patients with DC with a palpable cord.

The US pharmacoeconomic burden of DC is high. In a recent US-based study, employees with DC were found to have significantly greater medical costs, increased inpatient and outpatient resource utilization, and significantly greater indirect costs than those of employees without DC.

Quality of life is also affected by diverse hand activity limitations and functional impairment.

Consequently, DC is associated with substantial health-state utility decrements.

Real-world US-based evidence offering cost comparisons of DC treatments, including CCH and fasciectomy, is sparse. A recent retrospective study comparing costs of open fasciectomy and percutaneous needle aponeurotomy (NA) found that the mean direct costs of NA per patient were significantly lower than that for open fasciectomy ($4657 vs $11,240;

However, to date, cost assessment of CCH and fasciectomy has been limited to non-US countries.

 Thus, the objective of this study was to compare healthcare resource utilization (HRU) and costs of CCH and fasciectomy among adult DC patients from a US payer perspective.

Data was derived from IMS Health’s LifeLink Health Plan Claims Database, which is composed of fully adjudicated medical and pharmaceutical claims for nearly 80 million unique patients from 80 health plans across the United States. The database includes both inpatient and outpatient diagnoses (in 

International Classification of Diseases, Ninth Revision, Clinical Modification 

] format) and procedures (in Current Procedural Terminology and Healthcare Common Procedure Coding System formats), in addition to both retail and mail order prescription records. Available data on prescription records include the National Drug Code code and the Generic Product Identification code, as well as the quantity of the medication dispensed. Amounts charged by providers and amounts allowed and paid by health plans are available for all services rendered, including the dates of service for all claims. Additional data elements include demographic variables (eg, age, gender, geographic region), product type (eg, health maintenance organization [HMO], preferred provider organization), payer type (eg, commercial, self-pay), provider specialty, and start and stop dates for plan enrollment.

This was a retrospective database study of 2 mutually exclusive cohorts with all patients having at least 1 outpatient claim for either CCH or fasciectomy between February 1, 2010, and December 31, 2011 (selection window); the date of the first such claim within the selection window was designated as the index date.

To be included in either cohort, patients had to be at least 18 years of age in the year in which their index date fell, and be continuously enrolled during the study period (12 months pre- and post index); had no claims for a DC treatment in the pre-index period (ie, be new to treatment), and had evidence of only a single finger being treated on the index date. Patients were excluded if they were older than 65 years and also had incomplete claims data (patients older than 65 years with complete data were retained) or lacked a claim with a DC diagnosis code (

 718.44, 728.6) at any point in the 12-month pre-index period.

In addition to patient demographic and clinical characteristics—including a comorbidity profile as measured by the Charlson Comorbidity Index (CCI)&mdash;total pharmacy and overall healthcare costs were measured for the 12-month pre-index period as a broad measure of severity (patient demographics were measured as of the index date or pre-index period). DC-specific HRU and costs of all inpatient, outpatient, and pharmacy services were examined for the 12-month post index period. Measures of interest included the frequency of pharmacy prescriptions; outpatient services including emergency department visits, physician office visits, laboratory and pathology tests, radiological examinations, surgical services, and ancillary services (physical and occupational therapies); and inpatient hospital admissions and costs (allowed amounts) associated with these services.

Demographic and clinical characteristics, HRU, and patient costs were described using frequency and percentage distributions for categorical variables and descriptive statistics (mean, SD, and median) for continuous and count variables. As these were unmatched cohorts, 

 values using Pearson’s χ2 test for categorical variables and the nonparametric Wilcoxon rank-sum test for continuous variables were generated. A 

value of <.05 was considered to be statistically significant.

Multivariable analysis was performed to account for baseline differences between the 2 cohorts of interest. A generalized linear model with identity link was developed to describe the change in disease-specific costs from preto post index period, controlling for baseline demographic and clinical characteristics.

All statistical analyses were conducted using SAS version 9.2 (SAS Institute, Cary, North Carolina). Results are presented in 2012 US dollars.

Following the application of the inclusion and exclusion criteria, there were 309 CCH and 1264 fasciectomy patients remaining for analysis. On average, CCH patients were significantly older than fasciectomy patients (64.28 years vs 61.50; 

<.0001). There was no significant difference in the gender distribution of the cohorts. A greater proportion of CCH patients resided in the southern part of the United States compared with fasciectomy patients (38.19% vs 34.97%; 

= .0282), with most of the patients in both cohorts having PPO insurance (CCH 67.96%, fasciectomy 74.76%) (

Medication use in the pre-index period was similar across both cohorts, though a greater proportion of CCH patients had evidence of tetracycline derivative antibiotics compared with fasciectomy patients (9.1% vs 5.5%; 

= .0242). Both cohorts were similar with regard to selected comorbidities in the pre-index period, although CCH patients had a higher average CCI compared with fasciectomy patients (1.15 [median 0.0] vs 0.85 [median 0.0]; 

= .0213). CCH patients had both higher pre-index total pharmacy costs than fasciectomy patients ($2967.54 [median $1296.48] vs $2523.58 [median $818.11]; 

= .0012) and total healthcare costs than fasciectomy patients ($13,776.83 [median $5723.02] vs $10,213.06 [median $4493.28]) (

Over the 12-month post index period, there was no significant difference in the total number of pharmacy prescriptions filled by patients in each cohort. CCH patients had a greater number of physician office visits compared with fasciectomy patients (2.68 [median 2.00] vs 2.64 [median 0.00]; 

 <.0001). However, fasciectomy patients had greater resource utilization in several other healthcare services compared with CCH patients: laboratory and pathology claims (0.97 [median 1.00] vs 0.05 [median 0.00]; 

<.0001); radiology examinations (0.16 [median 0.00] vs 0.06 [median 0.00]; 

= .0037); anesthesia (2.73 [median 3.00] vs 0.23 [median 0.00]; 

<.0001); facility visits (25.84 [median 13.00] vs 2.35 [median 0.00]; 

<.0001); physical therapy (21.13 [median 0.00] vs 7.56 [median 0.00]; 

<.0001); and occupational therapy (5.29 [median 0.00] vs 1.59 [median 0.00];

Unadjusted Disease-Specific Direct Medical Costs

On average, fasciectomy patients had significantly higher disease-specific total overall costs (allowed amount) compared with CCH patients ($5408.48 [median $4263.78] vs $4844.06 [median $4095.56]; 

= .0083). Similarly, fasciectomy patients had greater outpatient costs, as well ($5279.21 [median $4196.71] vs $1609.65 [median $608.64]; 

<.0001). Costs for laboratory and pathology (

= .0053), surgical services (eg, anesthesia and facility visits) (

= .0118) were all significantly greater for fasciectomy patients compared with CCH patients (

). The largest component of CCH disease-specific costs over the post index period were due to pharmacy (62%), while outpatient costs (98%) were the largest driver of fasciectomy disease-specific costs over the post index period (

Adjusted Disease-Specific Direct Medical Costs

After adjusting for demographic and clinical characteristics, patients who had an initial treatment of fasciectomy had a change in overall disease-specific costs that was $548 more than that for CCH (parameter estimate = 548.423; 95% CI, —40.203 to 1137.048; not statistically significant). Patients with an unknown health plan type (compared with HMO), who were self-insured (compared with commercial), or whose prescriber was a rheumatologist (compared with a practitioner of another specialty) were more likely to have a greater change in overall disease-specific costs (all statistically significant). Patients whose prescriber was an orthopedic surgeon or a general surgeon (compared with a practitioner of another specialty), had prior use of cortisone, or whose CCI score was between 2 and 3 (compared with 0) were less likely to have a greater change in overall disease-specific costs (all statistically significant) (

This is the first study that compared HRU and costs of CCH and fasciectomy among adult DC patients in the United States. Unadjusted results suggested that the 1-year DC-specific costs of fasciectomy were significantly higher than those for CCH. These differences were predominantly driven by increased costs associated with laboratory and pathology tests, surgical services (eg, anesthesia and facility visits), and ancillary services (eg, physical and occupational therapies), perhaps related to a difference in CCI scores between the cohorts of interest. However, after adjusting for baseline demographic and clinical characteristics, the difference between the change in costs for CCH and fasciectomy was not statistically significant. The difference between univariate and multivariate analyses may have been due to the fact that the study assessed costs of DC treatments over a 12-month follow-up period. A longer duration of follow-up may have helped capture the long-term cost differences between CCH and fasciectomy, with potentially higher long-term costs associated with fasciectomy. Physical therapy is typically required for up to several months following surgery to maintain positive results

; CCH was only approved for use in the United States in February 2010, so a longer duration of follow-up was not feasible when this study was conducted.

Currently, there is no published literature available with which the findings of this study can be directly compared. Studies to date in the United States have focused on the less commonly used DC treatments such as open fasciotomy or NA. A recent Spanish study assessed the costs of CCH and fasciectomy at a single site and found that mean per patient costs at the time of treatment with CCH were lower than that for fasciectomy (€952 vs €1961, or $1206 vs $2484).

In addition to different settings of care, the study had a smaller sample size; hence, results may not be comparable with the current study. A large retrospective database analysis in England found that the mean annual per patient cost of fasciectomy procedures ranged from £2750 ($4406) for palmar fasciectomy to £9208 ($14,751) for dermofasciectomy in 2011.

Cost of fasciectomy from the current study falls between that range.

Results should be interpreted in light of certain limitations of the study. As with all administrative claims analyses, it should be noted that claims are collected for payment purposes, rather than research purposes, and the analysis is constrained by the codes, which may include coding errors and undercoding contained in claims. The data and the perspective limited this cost analysis to direct cost estimation. Since DC is associated with substantial indirect costs,

the total healthcare costs in the current study may underestimate the overall costs of CCH and fasciectomy treatments. Clinical measures, such as degree of contracture and recurrence data for the treated patients, were not available in the claims data to compare between the treatment arms. Claims data enabled us to focus on commercial managed care patients, but the findings may not be generalizable to patients with other types of healthcare plans, such as traditional Medicare.

A study in a larger database that has a CCH follow-up period that exceeds the one used in this study (12 months) may help yield a more confirmatory disease-specific cost comparison of CCH and fasciectomy.

Aspects of this work were presented at the Academy of Managed Care Pharmacy’s 26th Annual Meeting & Expo in Tampa, FL, on April 1-4, 2014.

Articles

A retrospective cohort analysis was conducted to compare disease-specific healthcare resource utilization and the costs of collagenase clostridium histolyticum and fasciectomy among adult Dupuytrenâ€™s contracture patients.