Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy.

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619.

A cost-consequence analysis of parecoxib and opioids vs opioids alone for postoperative pain: Chinese perspective.

PURPOSE: The use of parecoxib plus opioids for postoperative analgesia in noncardiac surgical patients seems to be cost-saving in Europe due to a reduction in opioid use and opioid-related adverse events. Given the lack of information on postoperative analgesic use in Asia, this study assessed the economic consequences of the addition of parecoxib to opioids vs opioids alone to treat postsurgical pain in China. METHODS: A cost-consequence economic evaluation assessed direct medical costs related to opioid-related clinically meaningful events (CMEs) utilizing dosing information and reported frequency of events from a Phase III, randomized, double-blind, global clinical trial (PARA-0505-069) of parecoxib plus opioids vs opioids alone for 3 days following major orthopedic, abdominal, gynecologic, or noncardiac thoracic surgery requiring general or regional anesthesia. The cost of CMEs was calculated using information on resource utilization and unit costs provided by a panel of clinical experts in China. Sensitivity analyses were performed to test the robustness of the results. RESULTS: Patients treated with parecoxib plus opioids reported fewer CMEs (mean 0.62 vs 1.04 events per patient [P<0.0001]) compared with opioids alone for the 3-day postoperative period. This suggested a potential savings of 356 Chinese yuan (¥) per patient over the 3 days (total cost of ¥1,418 for parecoxib plus opioids vs ¥1,774 with opioid use alone). CONCLUSION: Fewer CMEs with parecoxib plus opioids suggest a reduction in medical resource utilization and reduced costs compared to opioids alone when modeling analgesic use in non-cardiac surgery patients in China.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled Clinical Trials.

OBJECTIVES: This analysis compared the therapeutic response of pregabalin in patients with neuropathic pain (NeP) who had been previously treated with gabapentin to the therapeutic response in patients who had not received gabapentin previously. METHODS: Data were pooled from 18 randomized, double-blind, placebo-controlled trials of pregabalin in patients with NeP. Pregabalin-mediated changes in pain and pain-related sleep interference scores, patient global impression of change scores at endpoint, and the occurrence of adverse events were compared between patients who had received gabapentin previously (+GBN) and patients who had not received gabapentin previously (-GBN). RESULTS: There were no significant differences between the -GBN and +GBN cohorts with regard to the extent of pain relief and relief of pain-related sleep interference for any dose of pregabalin (150, 300, 600, or 150 to 600 mg/day) at any time point (6, 8, or 12 weeks). Additionally, there was no significant difference in the distribution of patient global impression of change scores at study endpoint, or the occurrence of adverse events, between the -GBN and +GBN cohorts. DISCUSSION: The findings presented here support the idea that pregabalin may be used successfully to treat patients with NeP who may be refractory, respond inadequately, or are intolerant to gabapentin. These findings highlight the importance of tailoring treatment of NeP based on individual patient response to different treatments, including the trial of multiple agents within the same mechanistic class.

A retrospective, matched cohort study of potential drug-drug interaction prevalence and opioid utilization in a diabetic peripheral neuropathy population initiated on pregabalin or duloxetine.

BACKGROUND: Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients' encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization. METHODS: Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/2012, and ≥12 months pre- and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims. RESULTS: No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058). CONCLUSION: The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.

The association between lower back pain and health status, work productivity, and health care resource use in Japan.

INTRODUCTION: This study investigated the effect of pain severity on health status, work productivity, health care resource use, and costs among respondents with lower back pain (LBP), in Japan. MATERIALS AND METHODS: Data from the 2013 Japan National Health and Wellness Survey, a survey of Japanese adults, were analyzed (N=30,000). All respondents provided informed consent, and the protocol was institutional review board-approved. Respondents who reported experiencing LBP were propensity score-matched to those without LBP, based on demographics and health history. Using regression modeling, patients with mild, moderate, and severe pain were compared against matched controls, with respect to health status (Mental and Physical Component Summary scores, and health utilities from the Short Form(®)-36 Health Survey version 2), work productivity (Work Productivity and Activity Impairment - General Health version), health care resource use, and annual per-patient costs (estimated using published annual wages and resource use event costs). RESULTS: A total 1,897 patients reported experiencing LBP in the past month (6.32%); 52.45% reported their pain as mild, 32.79% as moderate, and 14.76% as severe. Increasing pain severity was associated with significantly lower levels of mental component scores (46.99 [mild], 42.93 [moderate], and 40.58 [severe] vs 48.10 [matched controls]), physical component scores (50.29 [mild], 46.74 [moderate], and 43.94 [severe] vs 52.93 [matched controls]), and health utilities (0.72 [mild], 0.66 [moderate], and 0.62 [severe] vs 0.76 [matched controls]) (all P<0.05). Indirect costs were significantly higher (P<0.05) among those with moderate (¥1.69 million [MM] [equivalent to $17,000, based on United States dollar exchange rates on September 1, 2014]) and severe (¥1.88 MM [$19,000]) pain, relative to matched controls (¥0.95 MM [$9,500]). Direct costs were only marginally different (P=0.05) between those with severe pain and matched controls (¥1.33 MM [$13,000] vs ¥0.54 MM [$5,000]). CONCLUSION: Increasing pain severity among respondents with LBP was associated with significantly worse health status, to a clinically-relevant degree, along with greater indirect and direct costs, in Japan.

Impact of potential pregabalin or duloxetine drug-drug interactions on health care costs and utilization among Medicare members with fibromyalgia.

PURPOSE: To examine the impact of newly initiated pregabalin or duloxetine treatment on fibromyalgia (FM) patients' encounters with potential drug-drug interactions (DDIs), the health care cost and utilization consequences of those interactions, and the impact of treatment on opioid utilization. PATIENTS AND METHODS: Subjects included those with an FM diagnosis, a pregabalin or duloxetine prescription claim (index event), ≥1 inpatient or ≥2 outpatient medical claims, and ≥12 months preindex and ≥6 postindex enrollment. Propensity score matching was used to help balance the pregabalin and duloxetine cohorts on baseline demographics and comorbidities. Potential DDIs were defined based on Micromedex 2.0 software and were identified by prescription claims. RESULTS: No significant differences in baseline characteristics were found between matched pregabalin (n=794) and duloxetine cohorts (n=794). Potential DDI prevalence was significantly greater (P<0.0001) among duloxetine subjects (71.9%) than among pregabalin subjects (4.0%). There were no significant differences in all-cause health care utilization or costs between pregabalin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($9,373 versus $7,228; P<0.0001) and higher mean number of outpatient visits/member (16.0 versus 13.0; P=0.0009) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a statistically significant difference between pregabalin and duloxetine subjects in their respective pre- versus post-differences in use of ≥1 long-acting opioids (1.6% and 3.4%, respectively; P=0.077). CONCLUSION: The significantly higher prevalence of potential DDIs and potential cost impact found in FM duloxetine subjects, relative to pregabalin subjects, underscore the importance of considering DDIs when selecting a treatment.

Relationship between self-reported low-back pain severity and other patient-reported outcomes: results from an observational study.

STUDY DESIGN: A cross-sectional observational study of physicians and patients with chronic low-back pain (CLBP) in the United States. OBJECTIVE: To evaluate the association of patient-reported CLBP severity with other patient-reported outcomes. SUMMARY OF BACKGROUND DATA: Appropriate management of patients with CLBP can be enhanced by understanding how patients perceive the severity of their CLBP. METHODS: Data were from the 2009 Adelphi Disease Specific Programme. Patients reported the severity of their CLBP condition by answering the question Please rate how your chronic lower back pain condition is today with responses of mild, moderate, and severe. Patient-reported severity was evaluated with respect to scores on standard patient self-report measures of pain, pain interference, health status, functional disability, work productivity, and questions addressing satisfaction with medications for treating CLBP. RESULTS: Of 1860 subjects in the CLBP database, 1363 (73.3%) agreed to complete the survey. This sample was similarly distributed between males (49%) and females (51%), with mean age 54.8 years: 52% were employed at least part-time. CLBP severity was rated as mild, moderate and severe by 28.6%, 53.3%, and 18.2% of patients, respectively. With increasing CLBP severity, significant differences were observed in increased pain (P<0.0001), pain interference with function (P<0.0001), and impairment while working due to CLBP (P<0.01), mainly due to presenteeism. Increased work impairment resulted in higher costs related to lost work productivity; annual lost productivity costs were estimated at $7080, $16,616, and $25,032 per patient for mild, moderate, and severe CLBP, respectively (P<0.0001 for pairwise comparisons). Patient satisfaction with pain-related medication was inversely associated with CLBP severity. CONCLUSIONS: The association between patient-reported CLBP severity and other patient-reported outcomes demonstrates that in the clinical setting, patient-reported CLBP severity provides an accurate and suitable indicator of patient-reported health status. This indicator may be useful for guiding management strategies for CLBP patients.

Therapy switching, augmentation, and discontinuation in patients with osteoarthritis and chronic low back pain.

BACKGROUND: Recommended pain treatments for osteoarthritis (OA) and chronic low back pain (CLBP) are suboptimal, and limited information is available regarding patterns of pharmacotherapy among patients with these conditions. AIMS: Evaluate patterns of therapy switching, augmentation, and discontinuation after treatment initiation with select pain medications in patients with OA and CLBP. METHODS: Using the U.K. The Health Improvement Network (THIN) database, OA and CLBP patients newly prescribed (index-event) nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs), cyclooxygenase-2 inhibitors (Cox-2s), acetaminophen, tramadol and weak or strong opioids were selected. Descriptive statistics, Kaplan-Meier analyses, and COX proportional hazards models were used to evaluate patterns of changes in pharmacotherapy during the 12-month postindex period. RESULTS: Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P values<0.0001) across the evaluated medication cohorts for both OA and CLBP patients. Discontinuation rates in OA patients were 91.9% (NS-NSAIDs), 86.9% (Cox-2s), 91.4% (acetaminophen), 89.7% (tramadol), 93.2% (weak opioids), and 84.3% (strong opioids); and in CLBP patients were 97.2% (NS-NSAIDs), 94.0% (Cox-2s), 95.0% (acetaminophen), 92.8% (tramadol), 97.0% (weak opioids), and 86.8% (strong opioids). The rates of switching (range 30.0% to 59.6%) and augmentation (range 7.5% to 15.2%) were lower. Estimated probability evaluations suggested that two-thirds of patients who switched, augmented, or discontinued therapy did so within the first couple of months, and a majority did so within 6-months of treatment initiation. CONCLUSIONS: This study demonstrates that therapy switching and discontinuation of select pain medications were common among OA and CLBP patients in the U.K. and may result from inadequate pain relief or undesirable side effects.

Relationship between patient-reported chronic low back pain severity and medication resources.

BACKGROUND: Characterization of chronic low back pain (CLBP) severity from a patient's perspective can provide a context within which management strategies may be determined and therapeutic outcomes evaluated. OBJECTIVE: The aim of our study was to evaluate the association between patient-rated CLBP severity and medication resources. METHODS: Data were drawn from the Adelphi CLPB Disease Specific Programmme, a cross-sectional study of patients undertaken between September and November 2009. Patients reported the severity of their CLBP by answering the statement "Please rate how your chronic lower back pain condition is today" with responses of "mild," "moderate," or "severe." Severity was evaluated relative to physician-reported use of medications for the relief of CLBP and patient-reported satisfaction with pain relief and medications. RESULTS: Data from 170 physicians and 1363 patients (mean age 55 years; 52.3% female) were analyzed. CLBP severity was rated as mild, moderate, and severe by 28.3%, 52.8%, and 18.0% of patients, respectively. Physician-reported analgesia requirements increased with CLBP severity (P < 0.05). Opioids, nonsteroidal antiinflammatory drugs, and muscle relaxants were the most commonly prescribed medications for CLBP. Opioid prescriptions increased with increasing severity (P < 0.05), and nonsteroidal antiinflammatory drug prescriptions declined. Purchase of over-the-counter medications was similar across severity categories (23%-26% of patients), but the monthly amount spent on over-the-counter drugs was more than twice as high in patients with severe CLBP ($29.90) than in other severity categories. Patient and physician satisfaction with pain-related medication was inversely associated with CLBP severity; inadequate response was the primary reason for physician dissatisfaction. Factors limiting generalizability include potential differences between participants and those who refused to participate; potential misdiagnosis of CLBP in a proportion of patients; and an inability for cause-and-effect imputation due to the cross-sectional nature of the study. CONCLUSIONS: The relationship between patient-reported CLBP severity and medication prescribing patterns suggests that this rapid assessment may be of value for informing decisions regarding treatment options. The data also suggest that despite greater use of medications at greater CLBP severity, current options remain less than optimal in providing analgesic efficacy.

Relationship between patient-reported disease severity in osteoarthritis and self-reported pain, function and work productivity.

INTRODUCTION: Understanding the relationship between patient-reported osteoarthritis (OA) severity and other patient-reported outcomes in the real-world clinical setting can provide a basis for appropriate patient management. The objective of this study was to determine how patient-reported OA severity correlates with patient-reported outcomes including pain, function and productivity. METHODS: We used the Adelphi Disease Specific Programme (DSP) for OA, a database aggregated from large, multinational, observational studies for specific chronic diseases. Data were obtained based on a 0 to 100 mm pain visual analogue scale (VAS) and a series of questions including functioning (that is, activities of daily living) and work productivity. OA severity was rated by the patients based on the question "How bad would you say your arthritis is now?" with potential responses of "mild," "moderate," and "severe." Regression models and chi-square analyses were used to evaluate the relationships between self-reported OA severity and other outcomes. RESULTS: Of 998 subjects in the OA DSP U.S. database, 714 (72.5%) agreed to participate. This sample was predominantly female (61.7%) with a mean age of 63.8 ± 12.9 years. Increased OA severity was associated with an older population (P < 0.05). With increasing OA severity (mild, moderate, severe), statistically significant differences (P < 0.05) were observed in increased pain VAS scores (23.5, 50.2, 70.8, respectively), lower functioning outcomes, and a higher percent of overall work impairment due to OA (17%, 37%, 48%, respectively). The increased work impairment at greater severity levels also resulted in higher costs related to lost work productivity, with annual costs due to lost productivity estimated at $6,096, $13,2510, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively (P < 0.05 for pairwise comparisons). CONCLUSIONS: In the clinical practice setting, patient-reported OA severity was associated with other key patient-reported outcomes and thus may provide an accurate and tangible assessment of patients' perceptions of their disease. Identifying OA patients by their perceived severity level may be of benefit to patients and health-care providers when choosing treatment options aimed at reducing pain, and improving function and productivity.

Psychometric properties of a single-item scale to assess sleep quality among individuals with fibromyalgia.

BACKGROUND: Sleep disturbances are a common and bothersome symptom of fibromyalgia (FM). This study reports psychometric properties of a single-item scale to assess sleep quality among individuals with FM. METHODS: Analyses were based on data from two randomized, double-blind, placebo-controlled trials of pregabalin (studies 1056 and 1077). In a daily diary, patients reported the quality of their sleep on a numeric rating scale ranging from 0 ("best possible sleep") to 10 ("worst possible sleep"). Test re-test reliability of the Sleep Quality Scale was evaluated by computing intraclass correlation coefficients. Pearson correlation coefficients were computed between baseline Sleep Quality scores and baseline pain diary and Medical Outcomes Study (MOS) Sleep scores. Responsiveness to treatment was evaluated by standardized effect sizes computed as the difference between least squares mean changes in Sleep Quality scores in the pregabalin and placebo groups divided by the standard deviation of Sleep Quality scores across all patients at baseline. RESULTS: Studies 1056 and 1077 included 748 and 745 patients, respectively. Most patients were female (study 1056: 94.4%; study 1077: 94.5%) and white (study 1056: 90.2%; study 1077: 91.0%). Mean ages were 48.8 years (study 1056) and 50.1 years (study 1077). Test re-test reliability coefficients of the Sleep Quality Scale were 0.91 and 0.90 in the 1056 and 1077 studies, respectively. Pearson correlation coefficients between baseline Sleep Quality scores and baseline pain diary scores were 0.64 (p < 0.001) and 0.58 (p < 0.001) in the 1056 and 1077 studies, respectively. Correlations between the Sleep Quality Scale and the MOS Sleep subscales were statistically significant (p < 0.01), except for the MOS Snoring subscale. Across both studies, standardized effect sizes were generally moderate (0.46 to 0.52) for the 300 mg group and moderate (0.59) or moderate-to-large (0.70) for the 450 mg group. In study 1056, the effect size for the 600 mg group was moderate-to-large (0.73). In study 1077, the effect size for the 600 mg group was large (0.82). CONCLUSION: These results provide evidence of the reproducibility, convergent validity, and responsiveness to treatment of the Sleep Quality Scale and provide a foundation for its further use and evaluation in FM patients.

Minimal clinically important difference in the fibromyalgia impact questionnaire.

OBJECTIVE: The Fibromyalgia Impact Questionnaire (FIQ) is a disease-specific composite instrument that measures the effect of problems experienced by patients with fibromyalgia (FM). Utilization of the FIQ in measuring changes due to interventions in FM requires derivation of a clinically meaningful change for that instrument. Analyses were conducted to estimate the minimal clinically important difference (MCID), and to propose FIQ severity categories. METHODS: Data from 3 similarly designed, 3-month placebo-controlled, clinical treatment trials of pregabalin 300, 450, and 600 mg/day in patients with FM were modeled to estimate the change in the mean FIQ total and stiffness items corresponding to each category on the Patient Global Impression of Change. FIQ severity categories were modeled and determined using established pain severity cutpoints as an anchor. RESULTS: A total of 2228 patients, mean age 49 years, 93% women, with a mean baseline FIQ total score of 62 were treated in the 3 studies. Estimated MCID on a given measure were similar across the studies. In a pooled analysis the estimated MCID (95% confidence interval) was 14% (13; 15) and for FIQ stiffness it was 13% (12; 14). In the severity analysis a FIQ total score from 0 to <39 was found to represent a mild effect, >or= 39 to <59 a moderate effect, and >or=59 to 100 a severe effect. CONCLUSION: The analysis indicates that a 14% change in the FIQ total score is clinically relevant, and results of these analyses should enhance the clinical utility of the FIQ in research and practice.

Painful diabetic neuropathy: a cross-sectional survey of health state impairment and treatment patterns.

AIMS: To determine the patient burden of painful diabetic peripheral neuropathy (DPN) with respect to pain intensity and impact on patient functioning and to characterize relevant DPN treatment patterns. METHODS: Patients (n=140) with painful DPN identified during an observational survey of neuropathic pain syndromes in six European countries were included in the current analysis. Patients primarily recruited from community-based general practices answered a questionnaire that included pain severity and interference items from the modified Short-Form Brief Pain Inventory, the EuroQol survey, and questions related to productivity and health resource utilization. Physicians provided information on disease duration and current medications prescribed for painful DPN and pain-related comorbidities. RESULTS: The mean patient age was 65.6+/-11.2 years; 58% of the patients were >or=65 years. Duration of painful DPN was >1 year in 74% of patients. The mean Pain Severity Index was 5.0+/-2.0; 57% of patients reported moderate pain and 25% reported severe pain. Patients reported moderate interference with functioning despite 91% of patients reporting use of prescription medications for painful DPN including antiepileptics (56%), standard analgesics (63%), and amitriptyline (26%). Use of prescription medication for concomitant anxiety, depression, or sleep disturbance was reported for 43% of the patients. Disruption in employment was reported by 35% of the patients. Pain severity was significantly associated with reduced health state valuation (P<.001), greater pain interference scores (P<.001), greater employment disruption (P<.05), and more physician visits (P<.05). CONCLUSIONS: Painful DPN is associated with substantial patient burden resulting from interference with daily functioning, especially in patients with suboptimal pain management.