Patterns and Predictors of Medication Initiation in Diabetic Peripheral Neuropathy
Published Online: September 30, 2013
Chris M. Kozma, PhD; Terra l. Slaton, MS; Wing Chow, PharmD, MPH; and Marcia F. T. Rupnow, PhD
Of the more than 25 million Americans with diabetes, 1,2 up to 25% will develop painful diabetic peripheral neuropathy (DPN).3,4 Patients with DPN are generally in poorer health and incur higher healthcare resource utilization and costs than similar patients without DPN.5 Moreover, these patients are more likely to have greater numbers of comorbidities including musculoskeletal and other neuropathic pain–related conditions,6,7 increasing the likelihood that they will be prescribed pain medications. Given the clinical and economic burden associated with painful DPN, deeper understanding of factors that lead to medication initiation and medication choice is necessary for optimization of patient outcomes.
Painful DPN is a challenging chronic condition to manage and often requires a multimodal approach, in parallel or sequentially. Guidelines recommend antidepressants or anticonvulsants as fi rst-line treatments in the management of painful DPN.8-10 Of the antidepressants and anticonvulsants available in the United States, only duloxetine (an antidepressant) and pregabalin (an anticonvulsant) are indicated for the management of painful DPN.11,12 However, a metaanalysis of the available data suggested that other antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors) and anticonvulsants (gabapentin, sodium-channel blockers, membrane-stabilizing agents) also reduce chronic neuropathic pain more effectively than placebo.13
When antidepressants or anticonvulsants provide insufficient pain relief, guidelines for the management of painful DPN recommend opioid therapy.8-10 Limited literature examining treatment patterns within patients with painful DPN has suggested that opioids are a commonly used class of medications,7,13 but the reasons and timing for introducing an opioid regimen are not well documented. Given the chronic nature of DPN, treatment with a long-acting opioid (sustained-release, extended-release, or controlled-release formulations) is a recommended component of multimodal management strategies.14 Currently, only 1 opioid is indicated for the management of painful DPN in the United States (tapentadol extended release).15 Nonetheless, patients with DPN are up to 10 times more likely to receive a short-acting opioid than a long-acting opioid.2,7,16-20 To our knowledge, predictors for the use of long-acting or short-acting opioids in the management of painful DPN have not been explored previously.
The primary objective of this analysis was to investigate predictors of medication initiation and type of medication initiated in newly diagnosed DPN patients.
The data source for this analysis was employer-based claims from the MarketScan Research Database.21 The annual medical databases include private-sector health data from approximately 100 payers and more than 500 million claim records. The database represents the medical experience of insured employees and their dependents for active employees, early retirees, those who continue on COBRA, and Medicare-eligible retirees with employer-provided Medicare Supplemental plans. The database includes integrated patient-level data for inpatient, outpatient, and drug claims, as well as insurance eligibility. The database is de-identified and compliant with the Health Insurance Portability and Accountability Act of 1996. As such, no institutional review board approval was necessary.
This retrospective analysis included claims from January 1, 2005, through December 31, 2009 (Figure 1). A diagnosis of DPN was identified from International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 250.6X (diabetes with neurologic manifestations) or 357.2X (polyneuropathy in diabetes). The index date was the date of the first principal diagnosis of DPN in the identifi cation window (January 1, 2006, to June 30, 2009), which was selected to allow for analysis of claims data for 360 days preindex through 180 days postindex. To be eligible for inclusion, patients were required to be at least 18 years of age at the index date and continuously eligible for insurance plan and pharmacy coverage throughout their preindex and postindex periods. Patients were excluded if they had a diagnosis of DPN in the 360-day preindex period (ie, only “newly” diagnosed patients were analyzed).
Patients were divided into 2 cohorts: the newly initiated medication group and the initially untreated group. Because prescriptions were not linked to a specifi c diagnosis, rules were defi ned to identify patients who received medications for the DPN diagnoses. The goal of the rules was to create a high degree of confidence that the new medication therapy was related to the DPN diagnosis. The newly initiated medication group included patients who received a new prescription for a DPN-related medication (Appendix) within 14 days postindex. The 14-day window was selected to identify medicationsthat were likely to have been initiated for the new DPN diagnosis; it was long enough to allow patients up to 2 weeks to fill their new prescription after the DPN diagnosis, but short enough to exclude DPN-related medications that were prescribed for subsequent diagnoses. Patients in the newly initiated medication group could have used other medications (including another medication from the same category) previously, but they were excluded from the analysis if they had another claim in the 360-day preindex period for the same medication (eg, generic level) that they received within 14 days postindex.
To increase certainty that patients were using medications related to DPN and not for other purposes, patients in the newly initiated medication group were excluded from the analysis if they had any of the following diagnoses between the DPN diagnosis and the newly initiated medication: a newly initiated antidepressant and a mental health diagnosis (ICD-9-CM codes 290.xx-319.xx); a newly initiated anticonvulsant and a diagnosis of epilepsy and recurrent seizures or convulsions (ICD-9-CM codes 345.xx or 780.3); a newly initiated antidementia agent and a diagnosis of a mental disorder or disease of the nervous and sense organs (ICD-9-CM codes 290.xx-319. xx or 320.xx-389.xx); or a newly initiated antihypertensive or antiarrhythmic agent and disease of the circulatory system (ICD-9-CM codes 309.xx-459.xx).
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