At a Glance Original Research Original Practical Implications e104 Author Information e119 Web Exclusive www.ajpblive.com Patterns and Predictors of Medication Initiation in Diabetic Peripheral Neuropathy Chris M. Kozma, PhD; Terra L. Slaton, MS; Wing Chow, PharmD, MPH; and Marcia F. T. Rupnow, PhD f the more than 25 million Americans with dia- 1,2 betes, up to 25% will develop painful diabetic ABSTRACT 3,4 O peripheral neuropathy (DPN). Patients with DPN Objectives: To investigate patterns and predictors of medication are generally in poorer health and incur higher healthcare initiation and type of medication initiated in patients with newly resource utilization and costs than similar patients without diagnosed diabetic peripheral neuropathy (DPN). DPN.5 Moreover, these patients are more likely to have Study Design: Retrospective analysis of a nationwide administra- greater numbers of comorbidities including musculoskeletal tive claims database. and other neuropathic pain–related conditions,6,7 increasing Methods: Adults with a new principal DPN diagnosis were categorized as initially untreated if they had no newly initiated DPN- the likelihood that they will be prescribed pain medications. related medication within the fi rst 14 days after diagnosis. Bivariate Given the clinical and economic burden associated with logistic regression evaluated predictors for newly initiating medica- painful DPN, deeper understanding of factors that lead to tion versus being initially untreated. Multinomial logistic regression medication initiation and medication choice is necessary for evaluated predictors for each medication category (antidepres- optimization of patient outcomes. sants, anticonvulsants, or multiple medications versus opioids). Painful DPN is a challenging chronic condition to man- Results: Of 53,753 patients with DPN, 46,335 (86%) were age and often requires a multimodal approach, in parallel initially untreated and 7418 (14%) newly initiated an anticon- vulsant (48%), opioid (28%), antidepressant (18%), or multiple or sequentially. Guidelines recommend antidepressants or medications (6%). Having a preindex claim for an anticonvulsant, anticonvulsants as fi rst-line treatments in the management of antidepressant, or weak opioid predicted newly initiating another painful DPN.8-10 Of the antidepressants and anticonvulsants DPN-related medication. A weak opioid preindex predicted switch- available in the United States, only duloxetine (an antide- ing to another medication category after diagnosis and a strong pressant) and pregabalin (an anticonvulsant) are indicated opioid preindex predicted switching to an antidepressant or multiple medications. A preindex anticonvulsant predicted switch- for the management of painful DPN.11,12 However, a meta- ing to an opioid. A preindex antidepressant was not predictive of analysis of the available data suggested that other antidepres- switching. Of the patients who newly initiated medication, 28% had sants (tricyclic antidepressants, selective serotonin reuptake received an opioid preindex and 43% to 74% received an opioid inhibitors) and anticonvulsants (gabapentin, sodium-channel between 14 and 180 days postindex. blockers, membrane-stabilizing agents) also reduce chronic Conclusions: Prior medication use is the most signifi cant predic- neuropathic pain more effectively than placebo.13 tor of whether patients initiate a new medication at the time of When antidepressants or anticonvulsants provide insuf- a new DPN diagnosis, as well as what type of medication they receive. Opioid use is common before and after starting a new fi cient pain relief, guidelines for the management of pain- medication for DPN. ful DPN recommend opioid therapy.8-10 Limited literature Am J Pharm Benefi ts. 2013;5(5):e111-e121 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 introduc- ing 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 www.ajpblive.com Vol. 5, No. 5 • The American Journal of Pharmacy Benefi ts e111 I Kozma • Slaton • Chow • Rupnow The index date was the date of the fi rst principal PRACTICAL IMPLICATIONS diagnosis of DPN in the identifi cation window Improved understanding of pain progression and consideration of what constitutes (January 1, 2006, to June 30, 2009), which was optimal pain management are needed in planning for diabetic peripheral neuropathy selected to allow for analysis of claims data for (DPN) medication pharmacy benefi ts. 360 days preindex through 180 days postindex. I At DPN diagnosis, 14% of patients initiated a DPN-related medication, mostly an To be eligible for inclusion, patients were re- anticonvulsant or antidepressant (66%), followed by opioids (28%) and combina- quired to be at least 18 years of age at the in- tion treatment (6%). dex date and continuously eligible for insurance I Having a DPN-related medication claim before DPN diagnosis predicted initiating plan and pharmacy coverage throughout their another DPN-related medication at diagnosis, illustrating the diffi culties in fi nding optimal regimens. preindex and postindex periods. Patients were excluded if they had a diagnosis of DPN in the I Many patients received opioids before or after their diagnosis. 360-day preindex period (ie, only “newly” diag- nosed patients were analyzed). Patients were divided into 2 cohorts: the new- ly initiated medication group and the initially un- for the management of painful DPN in the United States treated group. Because prescriptions were not linked to a (tapentadol extended release).15 Nonetheless, patients specifi c diagnosis, rules were defi ned to identify patients with DPN are up to 10 times more likely to receive a who received medications for the DPN diagnoses. The short-acting opioid than a long-acting opioid.2,7,16-20 To goal of the rules was to create a high degree of confi dence our knowledge, predictors for the use of long-acting or that the new medication therapy was related to the DPN short-acting opioids in the management of painful DPN diagnosis. The newly initiated medication group included have not been explored previously. patients who received a new prescription for a DPN-re- The primary objective of this analysis was to investi- lated medication (Appendix) within 14 days postindex. gate predictors of medication initiation and type of medi- The 14-day window was selected to identify medications cation initiated in newly diagnosed DPN patients. that were likely to have been initiated for the new DPN diagnosis; it was long enough to allow patients up to 2 METHODS weeks to fi ll their new prescription after the DPN diagno- Data Source sis, but short enough to exclude DPN-related medications The data source for this analysis was employer-based that were prescribed for subsequent diagnoses. Patients claims from the MarketScan Research Database.21 The an- in the newly initiated medication group could have used nual medical databases include private-sector health data other medications (including another medication from the from approximately 100 payers and more than 500 million same category) previously, but they were excluded from claim records. The database represents the medical experi- the analysis if they had another claim in the 360-day pre- ence of insured employees and their dependents for active index period for the same medication (eg, generic level) employees, early retirees, those who continue on COBRA, that they received within 14 days postindex. and Medicare-eligible retirees with employer-provided To increase certainty that patients were using medica- Medicare Supplemental plans. The database includes in- tions related to DPN and not for other purposes, patients tegrated patient-level data for inpatient, outpatient, and in the newly initiated medication group were excluded drug claims, as well as insurance eligibility. The database from the analysis if they had any of the following diagno- is de-identifi ed and compliant with the Health Insurance ses between the DPN diagnosis and the newly initiated Portability and Accountability Act of 1996. As such, no in- medication: a newly initiated antidepressant and a men- stitutional review board approval was necessary. tal health diagnosis (ICD-9-CM codes 290.xx-319.xx); a newly initiated anticonvulsant and a diagnosis of epilepsy Study Design and recurrent seizures or convulsions (ICD-9-CM codes This retrospective analysis included claims from Janu- 345.xx or 780.3); a newly initiated antidementia agent ary 1, 2005, through December 31, 2009 (Figure 1). A and a diagnosis of a mental disorder or disease of the diagnosis of DPN was identifi ed from International Clas- nervous and sense organs (ICD-9-CM codes 290.xx-319. sifi cation of Diseases, 9th Revision, Clinical Modifi cation xx or 320.xx-389.xx); or a newly initiated antihyperten- (ICD-9-CM) codes 250.6X (diabetes with neurologic sive or antiarrhythmic agent and disease of the circulatory manifestations) or 357.2X (polyneuropathy in diabetes). system (ICD-9-CM codes 309.xx-459.xx). e112 The American Journal of Pharmacy Benefi ts • September/October 2013 www.ajpblive.com Patterns and Predictors of Medication Figure 1. Study Timeline ID window starts ID window ends 1/1/2006 6/30/2009 New Rx