Potential drug-induced constipation: A retrospective study using a Japanese claims database.

Background and Aim: Detailed clinical information regarding drug-induced constipation (DIC) is limited. This study aimed to investigate the real-world situation of DIC. Methods: This retrospective study used data from a Japanese claims database registered from 2014 to 2021. The constipation cohort included subjects with at least one record of treated constipation, while the non-constipation cohort was selected through random stratified sampling method, to match the constipation cohort by gender. The study population and control with at least one history of a known causative drug (CD) were matched 1:1 using propensity scores. The proportion of potential DIC (pDIC), the timing of diagnosis for pDIC, and the proportion of prescriptions by drug class for both the CDs and the laxatives were calculated, while logistic regression analysis was performed to explore additional associated factors. Results: Of the 4 533 905 subjects, 178 852 were eligible in both the study population and the control. The pDIC group comprised of 19 485 patients, which accounted for 10.9% of all treated constipation subjects, while the non-constipation with CD group had 10 430 subjects. The median duration between the recorded CD prescription and treated constipation was 38.0 days. The most frequently prescribed CD was cardiovascular drugs (47.9%). All CD classes, being male, and some comorbidities were associated with the occurrence of pDIC. Conclusion: The pDIC subjects accounted for about 11% of all treated constipation cases. Since DIC requires different treatment regimens compared to other constipation types, physicians should be cognizant to provide patients with optimized treatments.

Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.

OBJECTIVE: To comprehensively evaluate the efficacy, safety, patient symptoms, and quality-of-life (QoL) of lubiprostone, linaclotide, and elobixibat as treatment for chronic constipation (CC). DESIGN: Systematic literature review (SLR) and meta-analysis (MA). Literature searches were conducted on PubMed and Embase using the Ovid platform. METHODS: SLR including randomized controlled trials (RCTs) and observational studies was conducted to identify the overall efficacy and safety of lubiprostone, linaclotide, and elobixibat. Thereafter, MA was performed using only RCTs. The number needed to treat (NNT) and number needed to harm (NNH) analyses were additionally conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was efficacy regarding change in spontaneous bowel movements. Secondary outcomes included safety, constipation-related symptoms, and QoL. RESULTS: Twenty-four studies met the inclusion criteria for the SLR: 17 RCTs, 4 observational studies, and 3 single-arm trials. Feasibility assessment for the MA resulted in 14 studies available for safety data analysis, and 8 available for efficacy analysis, respectively. Three drugs showed similar efficacy in the MA and NNT analysis. However, the NNH analysis revealed distinct safety profiles: lubiprostone, linaclotide, and elobixibat were linked to the highest risk of nausea, diarrhea, and abdominal pain, respectively. CONCLUSION: The current study provides an updated overview of the efficacy, safety, patient symptoms, and QoL of the three drugs with different mechanisms of action for CC treatment.The findings could help physicians adopt an individualized approach for treating patients with CC in clinical practice.

Barriers to healthcare access in patients with chronic pain or potential migraine in Japan: a cross-sectional internet survey.

Purpose: Chronic pain and migraines often go untreated despite patient- and economic-related burdens (e.g., impaired quality of life and productivity). Understanding the reasons for non-treatment is important to enable interventions aimed at improving care-seeking behaviors. However, reports on disease-specific justifications for nontreatment in Japan are limited. We aimed to determine the barriers to healthcare access in untreated patients with chronic pain or migraines. Patients and methods: This was a non-interventional, cross-sectional, internet questionnaire survey of patients with chronic pain or migraines. The primary endpoint was to identify the reasons for untreated chronic pain or migraines. Secondary endpoints included factors associated with healthcare access, including patient background, patient-reported outcomes, and awareness of generic or authorized generic drugs (AG). Results: We surveyed 1,089 patients with chronic pain [605 (55.6%) untreated] and 932 patients with migraines [695 (74.6%) untreated] in 2021. The main reasons for not seeking treatment for chronic pain was "my pain is tolerable" and for migraine, "I can manage my pain with over-the-counter drugs." Background factors significantly associated with untreated chronic pain were younger age, less time required to access the nearest medical institution, less pain, higher activities of daily living (ADL) scores, and lower awareness of generic drugs and AG. Among patients with migraine, notable characteristics included being female, having shorter travel times to the nearest medical facility, residing in municipalities with populations under 50,000, experiencing moderate to severe pain, having higher ADL scores, and displaying lower awareness of AG. The AG awareness rate was 2-fold higher in treated patients than in untreated patients. Conclusion: Educating patients regarding the risks associated with pain and its underlying causes, availability of inexpensive treatment options, and location of appropriate treatment facilities may increase treatment rates.

Effectiveness and safety of lubiprostone after switching from stimulant laxatives in elderly patients with chronic constipation.

Background and Aim: Stimulant laxatives may cause electrolyte abnormalities, dehydration, and abdominal pain; their long-term use can lead to tolerance and subsequent refractory constipation. We investigated the effectiveness, safety, and quality of life after switching from stimulant laxatives to lubiprostone in elderly patients with chronic constipation (CC). Methods: This multicenter, interventional, open-label, single-arm, before-and-after comparison study enrolled 99 Japanese patients aged 65-90 years with CC who took stimulant laxatives for ≥2 weeks prior to switching to lubiprostone monotherapy. Results: The mean ± SD spontaneous defecations at Week 1 of 7.8 ± 6.2 times/week was not significantly different from that at baseline (8.3 ± 4.7). Spontaneous defecations were significantly reduced at Weeks 2 (-1.5 ± 4.0, P < 0.001) and 4 (-1.5 ± 3.7, P < 0.001). The Bristol Stool Form Scale score did not change from baseline (4.7 ± 0.9) at Weeks 1 (4.5 ± 1.3) or 4 (4.3 ± 1.3), but it did at Week 2 (4.3 ± 1.5, P < 0.05). The Patient Assessment of Constipation Quality of Life questionnaire score increased (0.36 ± 0.07, P < 0.001) after 28 days. Nausea was the only symptom that worsened from baseline and was the most frequently reported adverse drug reaction (15.2%). Conclusion: Switching to lubiprostone monotherapy for CC was not associated with significant concerns in short-term spontaneous defecation frequency and safety, but it might affect the efficacy and patient quality of life over 2 weeks. Careful treatment strategies facilitating gradual switching to lubiprostone monotherapy may be needed in patients using stimulant laxatives.

Dietary therapy for patients with chronic pancreatitis in Japan: a cross-sectional online survey of physicians and registered dietitians.

Background: This study was aimed towards understanding the current status of dietary therapy for patients with pancreatic exocrine insufficiency (PEI) in Japan and its alignment with Japanese recommendations for high-fat intake and concomitant high-potency pancreatic enzyme replacement therapy (PERT) by surveying treating physicians and registered dietitians. Methods: The 19-item physicians' online questionnaire collected data about the number of patients with PEI treated, methods used to assess PEI and nutritional status in patients with PEI, as well as provision of dietary guidance and details of treatment with PERT. The 10-item registered dietitians' online questionnaire captured data about the provision of dietary guidance, including setting (inpatient or outpatient) and details of nutritional guidance provided to patients. Results: Overall, 35 physicians and 23 dietitians completed the respective questionnaires. The primary cause of PEI in patients treated by physicians during the previous month was chronic pancreatitis (80.5%). Of 30 (86%) physicians who reported implementing dietary guidance for patients with PEI, less than half (43%) followed national guidelines and most (83%) implemented a low-fat diet. The use of PERT in recently treated patients with PEI was low. Amongst 11 (48%) dietitians who reported providing dietary guidance to patients with chronic pancreatitis and PEI, 7 (64%) recommended restricting fat intake in patients with uncompensated chronic pancreatitis. Dietitians overall were more likely to provide guidance about alcohol avoidance (91%) than smoking cessation (48%) to appropriate patients. Conclusion: This survey suggests that additional educational efforts are required to align the management practices of physicians and registered dietitians with evidence-based clinical practice guidelines for Japanese patients with chronic pancreatitis and PEI.

Perioperative Analgesics and Anesthesia as Risk Factors for Postoperative Chronic Opioid Use in Patients Undergoing Total Knee Arthroplasty: A Retrospective Cohort Study Using Japanese Hospital Claims Data.

BACKGROUND: Patients with chronic postsurgical pain are commonly prescribed opioids chronically because of refractory pain although chronic opioid use can cause various severe problems. OBJECTIVE: We aimed to investigate postoperative chronic opioid use and its association with perioperative pain management in patients who underwent a total knee arthroplasty in a Japanese real-world clinical setting. METHODS: We conducted a retrospective cohort study using an administrative claims database. We used a multivariate logistic regression analysis to examine the association between perioperative analgesic and anesthesia prescriptions and postoperative chronic opioid use. We calculated all-cause medication and medical costs for each patient. RESULTS: Of the 23,537,431 patient records, 14,325 patients met the criteria and were included in the analyses. There were 5.4% of patients with postoperative chronic opioid use. Perioperative prescriptions of weak opioids, strong and weak opioids, and the α2δ ligand were significantly associated with postoperative chronic opioid use (adjusted odds ratio [95% confidence interval], 7.22 [3.89, 13.41], 7.97 [5.07, 12.50], and 1.45 [1.13, 1.88], respectively). Perioperative combined prescriptions of general and local anesthesia were also significantly associated with postoperative chronic opioid use (3.37 [2.23, 5.08]). These medications and local anesthesia were more commonly prescribed on the day following surgery, after routinely used medications and general anesthesia were prescribed. The median total direct costs were approximately 1.3-fold higher among patients with postoperative chronic opioid use than those without postoperative chronic opioid use. CONCLUSIONS: Patients who require supplementary prescription of analgesics for acute postsurgical pain are at high risk of postoperative chronic opioid use and these prescriptions should be given careful consideration to mitigate the patient burden.

Efficacy of Combination Therapy with Pregabalin in Neuropathic Pain: A Preclinical Study in the Rat L5 Spinal Nerve Ligation Model.

Purpose: Neuropathic pain is sometimes difficult to manage because of limited efficacy of analgesic monotherapy even at high doses. Combination therapy may help address this issue, but there is little evidence for its effectiveness. Therefore, we evaluated the efficacy of combination therapy with pregabalin, an anchor drug for treating neuropathic pain, using the rat L5 spinal nerve ligation model. Methods: Experiments were performed on four-week-old L5 spinal nerve ligated male Sprague-Dawley rats. Mechanical allodynia was assessed using the von Frey test, where the 50% withdrawal threshold was evaluated for five drugs: pregabalin, duloxetine, venlafaxine, tramadol, and celecoxib. The single-drug experiment included 112 rats, where each drug was tested independently. Median effective doses (ED50s) were determined. Combinations of pregabalin with each of the other four drugs were tested (n=84). The 50% withdrawal threshold in the von Frey test was evaluated. The ED50 of each combination was determined experimentally. Isobolographic analyses were conducted to assess the synergistic potential of the drug combinations, excluding pregabalin-celecoxib, since the ED50 of celecoxib could not be determined. Results: In the single-drug experiment, all drugs except celecoxib resulted in a dose-dependent increase in the 50% withdrawal threshold 2 h after administration, with a maximum possible effect ranging from 4.4% to 79.6%. Similarly, all pregabalin combinations demonstrated a dose-dependent increase in the 50% withdrawal threshold, with pregabalin-tramadol showing the greatest increment. Isobolographic analysis of this combination revealed synergistic effects. Specifically, the combination index was γ=0.4 (<1). Combinations of pregabalin with duloxetine and venlafaxine demonstrated additive (γ=0.9) and antagonistic effects (γ=2.0), respectively. Conclusion: This study demonstrated that combination of pregabalin with tramadol has synergistic antiallodynic effects, while that with duloxetine has additive effects. Moreover, pregabalin combined with venlafaxine was potentially antagonistic. Pregabalin combined with tramadol may serve as a promising drug combination for the effective management of neuropathic pain.

Physician consultation rates and characteristics among workers with chronic pain or headache who participated in a behavioural change program: a retrospective database analysis using real-world healthcare data.

OBJECTIVE: To assess the potential benefit of a behavioural change programme in working individuals with chronic pain or headache, in the form of increased physician consultation. DESIGN: Retrospective observational database study. SETTING: Members of employment-based healthcare insurance in Japan. PARTICIPANTS: Individual-level data of working individuals aged <75 years from November 2019 through March 2020 were extracted from a database managed by MinaCare Co., Ltd. Included individuals had records of programme participation and chronic pain or headache (self-reported), and did not consult physicians for ≥3 months before programme participation. OUTCOME MEASURES: Physician consultation rates after participating in the programme were examined from December 2019 through March 2020, separately for chronic pain and headache. Baseline characteristics included age, pain numeric rating scale (NRS) score (for chronic pain), suspected migraine (for headache), labour productivity including absenteeism and presenteeism, and 4-month indirect costs in Japanese yen (JPY). RESULTS: The baseline mean age (±SD) of 506 individuals with chronic pain was 46.8±10.1 years; that of 352 individuals with headache was 43.6±9.9 years. Of those with chronic pain, 71.4% had an NRS score≥4, and 49.7% of those with headache had suspected migraine. Overall, 11.3% and 5.4% of those with chronic pain or headache consulted physicians, respectively. The mean baseline absenteeism and presenteeism were 1.5% and 19.1% in those with chronic pain, and 1.5% and 23.0% in those with headache. The baseline indirect costs were 586 941.6 JPY and 1 060 281.6 JPY among those with chronic pain or headache, respectively. CONCLUSION: Given that the individuals did not regularly consult physicians before the programme despite reporting substantial symptoms, our results suggest the potential benefit of educational programmes encouraging physician consultation. Further studies are required to evaluate how to effectively implement such educational programmes via healthcare insurers to reduce the burden of pain symptoms and overall medical costs.

The Use of a Network Analysis to Identify Associations and Temporal Patterns Among Non-communicable Diseases in Japan Based on a Large Medical Claims Database.

BACKGROUND: Reducing the considerable non-communicable disease (NCD) burden in the aging Japanese population depends on better understanding of the comorbid and temporal relationships between different NCDs. OBJECTIVE: We aimed to identify associations between NCDs and temporal patterns of NCDs in Japan using data from a large medical claims database. METHODS: The study used three-digit International Classification of Diseases, Tenth Revision codes for NCDs for employees and their dependents included in the MinaCare database, which covers the period since 2010. Associations between pairs of NCDs were assessed by calculating risk ratios. The calculated risk ratios were used to create a network of closely associated NCDs (risk ratio > 15, statistically significant) and to assess temporal patterns of NCD diagnoses (risk ratio ≥ 5). The Infomap algorithm was used to identify clusters of diseases for different sex and age strata. RESULTS: The analysis included 4,200,254 individuals (age < 65 years: 98%). Many of the temporal associations and patterns of the diseases of interest identified in this study were previously known. Regarding the diseases of interest, these associations can be classified as comorbidities, early manifestations initially diagnosed as something else, diseases attributable to or that cause the disease of interest, or caused by pharmacological treatment. International Classification of Diseases, Tenth Revision chapters that were most associated with other chapters included L Diseases of the skin and subcutaneous tissue. In the age-stratified and gender-stratified networks, clusters with the highest numbers of International Classification of Diseases, Tenth Revision codes included I Diseases of the circulatory system and F Mental and behavioral disorders. CONCLUSIONS: Our findings reinforce established associations between NCDs and underline the importance of comprehensive NCD care.

Association Between HbA1c Levels and Diabetic Peripheral Neuropathy: A Case-Control Study of Patients with Type 2 Diabetes Using Claims Data.

BACKGROUND: Evidence on the efficacy of glycemic control for diabetic peripheral neuropathy (DPN) is limited in patients with type 2 diabetes mellitus. Despite the known relationship between hemoglobin A1c (HbA1c) and DPN, the parameters (e.g., mean values or variability) that play an important role have not been elucidated. OBJECTIVE: The objective of this study was to explore factors associated with DPN, including long-term HbA1c parameters, among patients with type 2 diabetes, in a large-scale longitudinal study. METHODS: We conducted a case-control study using a medical claims database. We extracted data of patients with type 2 diabetes and disease records of DPN (indicating that they received treatment for DPN) and those without DPN records (controls), and matched for age, sex, index year, and duration since the first type 2 diabetes record. A logistic regression analysis was performed to explore factors associated with DPN, and a receiver-operating characteristic analysis to estimate the optimal mean HbA1c target. RESULTS: Of 1,792,037 patients with type 2 diabetes, data from 1632 patients (816 per group) were analyzed. The mean HbA1c levels in the 3-year observation period were 7.2 ± 1.0% in the DPN group and 6.9 ± 1.1% in the control group. Elevated 3-year mean HbA1c levels were significantly associated with DPN records (adjusted odds ratio: 1.23, 95% confidence interval 1.06-1.42), while HbA1c variability was not significantly associated. The mean HbA1c levels that discriminated between patients with and without DPN records were 6.5% (unadjusted) and 7.1% (adjusted). CONCLUSIONS: The development or progression of DPN in patients with type 2 diabetes was associated with the 3-year mean HbA1c level in real-world data.

Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan.

OBJECTIVES: The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. METHODS: This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer's perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. RESULTS: A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. CONCLUSION: The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients' future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.

Direct and Indirect Pathways for Health-Related Quality of Life Change from Pain Improvement in Neuropathic Pain Patients with Spine Diseases: Path Analysis with Structural Equation Modeling Using Non-Interventional Study Results of Pregabalin.

BACKGROUND: Chronic low back pain or chronic cervical pain often has a neuropathic pain (NeP) component and patients with these conditions complain of sleep deprivation, loss of physical function, and reduced productivity due to pain. The objective of this study was to clarify the pathway by which pain, sleep disturbance due to pain, and physical function status influence QOL measures in chronic low back pain patients with NeP associated with lumbar spine diseases (CLBP-NeP) and in chronic cervical pain patients with NeP associated with cervical spine diseases (CCP-NeP). METHODS: A model assuming pain numeric rating scale (NRS), pain-related sleep interference scale (PRSIS), and functional indices (Roland Morris Disability Questionnaire [RMDQ], Neck Disability index [NDI]) as factors that can affect outcomes such as QOL (calculated using EuroQoL 5 Dimensions (EQ-5D)), the Patient Global Impression of Change (PGIC), and the Clinical Global Impression of Change (CGIC) was developed using structural equation modeling. RESULTS: Overall trends were frequently observed in both patients with CLBP-NeP and CCP-NeP. Pain NRS had the largest comprehensive direct impact on QOL based on EQ-5D and an overall impression of changing symptoms. The effects of pain NRS on each outcome were largely due to direct pain-related effects; however, for EQ-5D, an indirect effect via functional improvement was the primary factor. CONCLUSION: Although the results of this study suggest that the indirect functional improvement of pain relief may not be recognized as a significant component of therapeutic effects by both physicians and patients, the pain-relieving intervention contributes directly to improvement of patients' overall QOL and also indirectly via functional improvement in Japanese primary care settings. Accordingly, to achieve the therapeutic goal for patients with NeP and minimize the impact of pain burden, our findings indicate that pain relief interventions are also crucial from the perspective of the patient's HRQOL.

Antidyslipidemic Drug Prescriptions and Lipid Control Status After Unfavorable Annual Health Checkup Results: A Retrospective Cohort Study Using a Health Insurance Database.

BACKGROUND: Japanese employers are obligated to offer employees annual health checkups and guidance programs for their health promotion and maintenance to prevent cardiovascular (CV) and lifestyle-related diseases. Under these programs, checkup recipients are notified of the checkup results, and in case of abnormal findings, employers are expected to provide employees with follow-up encouragement to change their behavior; for example, with medical consultations or lifestyle modifications. However, the effect of these programs on behavioral changes and their subsequent clinical outcomes has not been clearly assessed. OBJECTIVE: The aim of this study was to investigate changes in CV risk management behaviors after receiving unfavorable health checkup results on serum lipid levels among subjects without antidyslipidemic drug prescription and uncontrolled lipid levels and at elevated risk of CV events in a real-world setting. PATIENTS AND METHODS: This retrospective cohort study used a Japanese employment-based health insurance database managed by MinaCare Co., Ltd. This study analyzed the data from the annual health checkups of recipients aged 20-74 years with data on their low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), and triglyceride (TG) values from 2015 to 2017, who had uncontrolled lipid levels based on their checkup results at baseline in 2015, and without prescription records of antidyslipidemic drugs. Lipid status was considered uncontrolled if any of the following were detected: LDL-c ≥ 140 mg/dL, HDL-c < 40 mg/dL, or TG ≥ 150 mg/dL. Changes in antidyslipidemic drug prescription, as a primary CV risk management behavior measure, and in lipid control status in 2016 and 2017 were investigated. Potential factors associated with lipid control were also explored using logistic regression analysis. RESULTS: Among 154,421 subjects without antidyslipidemic drug prescription and with uncontrolled lipid levels in 2015, 93.6% remained without antidyslipidemic drug prescription in both 2016 and 2017. Of these subjects, 76.8% and 76.4% continued having uncontrolled lipid levels in 2016 and 2017, respectively. Fewer subjects without prescription achieved lipid control than those with prescription. Various factors were associated with lipid control, with high LDL-c as the greatest risk factor for uncontrolled lipid levels. CONCLUSIONS: These results suggest that most health checkup recipients may not have changed their behaviors; that is, they may have not sought medical treatment and continued having uncontrolled lipid levels in the years following the unfavorable health checkup results. To encourage subjects to initiate desirable behavioral changes, more practical support may be essential.

Effectiveness of Pregabalin Treatment for Neuropathic Pain in Patients with Spine Diseases: A Pooled Analysis of Two Multicenter Observational Studies in Japan.

PURPOSE: Neuropathic pain (NeP) is common among patients with chronic pain associated with spine diseases. Practical effectiveness of pregabalin, one of the first-line treatments for NeP, has not been evaluated in an entire population of patients with spine diseases, including various pathophysiological conditions. This pooled analysis aimed to evaluate the therapeutic value of pregabalin for chronic pain with NeP component in patients with spine diseases in routine primary care settings. PATIENTS AND METHODS: We pooled data from two 8-week prospective observational cohort studies for patients with chronic low back pain with accompanying lower limb pain (NeP component), and patients with chronic cervical pain and accompanying upper limb radiating pain (NeP component) in routine primary care settings in Japan. For both studies, patients were treated for 8 weeks with pregabalin (alone/with other analgesics) or usual care with conventional analgesics (eg, non-steroidal anti-inflammatory drugs). Changes in pain numerical rating scale (NRS), Pain-Related Sleep Interference Scale (PRSIS), and EuroQol 5-dimension 5-level (EQ-5D-5L) scores from baseline to week 8 were summarized and compared between the pregabalin and usual care groups, and also for subgroups of primary diagnosis. Safety was evaluated by adverse events (AEs) in the pregabalin group. RESULTS: The pooled dataset comprised 700 patients (pregabalin group: 302; usual care group: 398). All patient-reported outcomes (PRO) scores significantly improved from baseline to week 8 in the pregabalin than in the usual care group (NRS: P<0.0001; PRSIS: P<0.0001, and EQ-5D-5L: P=0.0006). Overall, all three PRO measures showed greater improvement in the pregabalin than in the usual care group, irrespective of the primary diagnosis. AEs were reported in 36.1% of the pregabalin group. CONCLUSION: This analysis suggested multi-faceted effectiveness of treatment with pregabalin from the patient's perspectives under a "real-world" practice in all patients with chronic NeP from various spine diseases.

Relationship of Annual Health Checkups with the Subject's Subsequent Behavior of Cardiovascular Risk Management in a Real-World Setting in Japan: A Retrospective Cohort Study on Changes in Antihypertensive Drug Prescription and Blood Pressure from 2015 to 2017.

BACKGROUND: In Japan, workers receive a health checkup annually, and based on the results, a follow-up health guidance or intervention is provided when deemed necessary. However, it remains unclear whether the current real-world health checkup and guidance programs in Japan successfully lead to behavioral changes or improvement of clinical outcomes in individuals who require cardiovascular (CV) risk management. OBJECTIVE: This study aimed to explore the association between health checkup and the subsequent behavior change in CV risk management in subjects with uncontrolled blood pressure (BP) without antihypertensive drug prescription, who can have increased risk of CV events. PATIENTS AND METHODS: This was a retrospective cohort study that used health-checkup and claims data from a Japanese healthcare database managed by MinaCare Co., Ltd. Of those aged 20-74 years with available data on systolic and diastolic BP from 2015 to 2017, data from individuals with uncontrolled BP who were not prescribed antihypertensive drugs within 6 months before their baseline health checkup in 2015 were extracted and analyzed. The primary outcome measures were changes in antihypertensive drug prescription and BP control status based on health-checkup results from the baseline year (2015) to 2017. CV risk-management behavior was also assessed using body mass index (BMI) and smoking status, as these are the major modifiable CV risk factors. RESULTS: Among 39,242 subjects with uncontrolled BP without antihypertensive drug prescription at baseline, 88.9% remained without prescription in 2016. Of the subjects without prescription, 62.9% continued to have uncontrolled BP. Both statuses of the major modifiable CV risk factors remained unchanged in 2016: 92.1% of obese subjects (BMI ≥ 25 kg/m2) at baseline remained obese, and 93.8% of smokers at baseline aged ≥ 40 years continued to smoke. Logistic regression analysis revealed that age 60-69 years (vs. 40-49 years), hypertension (HT) stage II (vs. stage I), HT stage III (vs. stage I), and BMI ≥ 25.0 kg/m2 (vs. < 25.0 kg/m2) were factors associated with uncontrolled BP in 2016 (subsequent year), regardless of antihypertensive drug prescription. CONCLUSIONS: Untreated HT for years increases the risk of CV events. These results suggest that current health-checkup and guidance programs are inadequately effective for behavioral change. Further practices for committing to lifestyle modifications and seeking medical advice based on their health-checkup results need to be undertaken to improve health behavior.

Treatment and Healthcare Cost Among Patients with Hip or Knee Osteoarthritis: A Cross-sectional Study Using a Real-world Claims Database in Japan Between 2013 and 2019.

BACKGROUND AND OBJECTIVES: The guidelines for osteoarthritis (OA) treatment recommend different therapies including pharmacotherapy, and several analgesic options are available for pain management. In Japan, research on hip and knee OA treatment trends is scarce and OA-related healthcare costs are unknown. Therefore, this study aimed to examine the treatment and healthcare cost trends among Japanese patients with hip or knee OA. METHODS: This was a cross-sectional study held between 2013 and 2019, using a medical claims database. The demographic and treatment characteristics of hip or knee OA patients for each year were descriptively analyzed and the medians for healthcare utilization and all-cause healthcare costs were calculated. RESULTS: The yearly mean age of 59,218 hip OA and 270,722 knee OA patients ranged from 66.3 to 68.6 years and 71.1 to 73.1 years, respectively. The prevalence of comorbidities was higher in knee OA than hip OA. In both groups, > 70% of patients were female, and the most common treatment was pain-related medication. In hip OA, topical and systemic nonsteroidal anti-inflammatory drugs (NSAIDs) were mostly used throughout the study period (34.1-41.4% and 32.0-40.3%, respectively). Similarly, in knee OA, topical and systemic NSAIDs were used in 58.3-63.3% and 36.5-46.0% patients, respectively. Increase in the use of acetaminophens (10.9% in hip OA and 10.2% in the knee OA) and weak opioids (3.7%, and 3.4%, respectively) from 2013 to 2019 were observed. Most patients were treated as outpatients in both groups. The median all-cause healthcare costs were approximately 35,000 JPY for hip OA and 74,000 JPY for knee OA. CONCLUSIONS: Although a considerable change in total healthcare cost was not observed in our study, the contents of medical treatment and cost breakdown were greatly altered due to the treatment and cost for OA itself, and the treatment and cost for comorbidities. Similar studies to investigate such a trend may help predict necessary resources and social needs. Thus, further investigation utilizing other databases is needed.

A Cost-Effectiveness Analysis Of Pregabalin For The Treatment Of Patients With Chronic Cervical Pain With A Neuropathic Component In Japan.

PURPOSE: To evaluate the cost-effectiveness of pregabalin versus other analgesics among patients with chronic cervical pain with neuropathic components during routine clinical practice in Japan. PATIENTS AND METHODS: The analysis considered patients with chronic cervical pain with a neuropathic pain component (radiating pain to the upper limb) and who were treated with pregabalin with or without other analgesics (pregabalin-containing treatments) or other analgesics alone (usual care) for 8 weeks. Other analgesics included non-steroidal anti-inflammatory drugs (NSAIDs), weak opioids, antidepressants, and antiepileptic drugs. A Markov cohort simulation model was constructed to estimate costs and effectiveness (in terms of quality-adjusted life-years, QALYs) of each treatment over a 12-month time horizon. In the model, patients transitioned among three states of pain severity (no/mild, moderate, and severe). Data were derived from a previous observational study (pregabalin-containing treatments, n = 138; usual care, n = 211). Cost inputs included medical costs and productivity losses. QALYs were calculated using the EuroQol five-dimensional, five-level questionnaire. The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to assess the robustness of results. RESULTS: From the payer's perspective, pregabalin-containing treatments were more costly (JPY 61,779 versus JPY 26,428) but also more effective (0.763 QALYs versus 0.727 QALYs) than the usual care, with an ICER of JPY 970,314 per QALY gained. From the societal perspective, which also included productivity losses, the ICER reduced to JPY 458,307 per QALY gained. One-way sensitivity analyses demonstrated the robustness of the results. Given a hypothetical threshold value of one additional QALY of JPY 5,000,000, the probability of pregabalin-containing treatments being cost-effective was 100%. CONCLUSION: Compared with using other analgesics alone, the use of pregabalin, alone or in addition to other analgesics, was cost-effective for the treatment of chronic cervical pain with a neuropathic pain component in Japan.

Effectiveness of pregabalin for treatment of chronic cervical radiculopathy with upper limb radiating pain: an 8-week, multicenter prospective observational study in Japanese primary care settings.

Background: Despite high prevalence of chronic neck pain in Japan and the negative impact pain has on patient's quality of life (QoL), the therapeutic value of pregabalin for chronic neck pain with a neuropathic pain (NeP) component has not been assessed in a typical Japanese health care setting. Methods: An 8-week, non-interventional, multicenter, observational study of Japanese adults (≥20 years) with chronic refractory cervical pain including a NeP element (for ≥12 weeks) and sleep disturbance on the Pain-Related Sleep-Interference Scale (PRSIS) ≥1 (from 0 "does not interfere with sleep" to 10 "completely interferes"). Patients received either usual care with conventional analgesics or pregabalin (150-600 mg/day) for 8 weeks. "Usual care" with analgesics or other treatment(s) was determined based on physician's best clinical judgment. Primary endpoint was change from baseline to week 8 in PRSIS. Secondary endpoints included: change from baseline to week 4 in PRSIS, and to week 4 and 8 in pain Numerical Rating Scale (NRS; from 0 "no pain" to 10 "worst possible pain"), and on the Neck Disability Index (NDI). Other assessments of QoL were undertaken. Safety was monitored. Results: Overall, 369 patients received pregabalin (n=145) or usual care (n=224). The median (range) dose of pregabalin was 49.6 (25.0-251.5) mg/day. Least-squares mean change in PRSIS from baseline to week 8 favored pregabalin (-1.167 vs -0.269; treatment difference -0.898 [95% CI -1.262, -0.535], P<0.001). Similar observations were seen at week 4 in favor of pregabalin versus usual care (P<0.001). Pregabalin significantly improved pain NRS and NDI scores at weeks 4 and 8 (all P<0.001). Improvements in QoL versus usual care were also observed. Pregabalin was generally well tolerated. Conclusion: In this open-label study, pregabalin improved PRSIS and resulted in clinically meaningful reductions in pain in Japanese patients with NeP associated with chronic cervical pain. ClinicalTrials.gov identifier: NCT02868359.

The efficacy of pregabalin for the treatment of neuropathic pain in Japanese subjects with moderate or severe baseline pain.

PURPOSE: Although analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP. PATIENTS AND METHODS: Data were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13-16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day. RESULTS: Mean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema. CONCLUSION: Pregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity. CLINICALTRIALSGOV IDENTIFIERS: NCT0039490130, NCT0055347522, NCT0040774524.

Clinical and economic burdens experienced by patients with painful diabetic peripheral neuropathy: An observational study using a Japanese claims database.

BACKGROUND: Diabetic peripheral neuropathy (DPN) may often be painful. Despite the high prevalence of painful DPN (pDPN) among patients with diabetes mellitus (DM), understanding of its clinical and economic burden is limited. This study aimed to describe the clinical and economic burdens faced by patients with pDPN in Japan, and compared them with those experienced by patients with DPN but without painful symptoms (non-pDPN). METHODS: This retrospective, observational study used data from a large-scale, hospital-based Japanese claims database collected from April 2008 to June 2015. Comorbidities, clinical departments visited, length of hospital stay, and medical costs for the period of ± 6 months from the diagnosis of pDPN or non-pDPN were described for each group. Glycemic control status was examined for each group for patients with glycated hemoglobin data. RESULTS: The data of 8,740 patients with pDPN (mean age 70.0 years, 53.4% male) and 12,592 patients with non-pDPN (mean age 67.7 years, 55.7% male) were analyzed. Patients with pDPN had more comorbidities than patients with non-pDPN; 48.7% and 30.9% of patients in the respective groups had 20 or more comorbidities. The median length of hospital stay was 5 days longer in patients with pDPN. The median total medical costs were higher in patients with pDPN (\517,762) than in patients with non-pDPN (\359,909). Patients with pDPN spent higher median costs for medications, but the costs for glycemic control drugs were similar in both groups. For 3,372 patients with glycated hemoglobin data, glycemic control was similar between the two groups. CONCLUSION: Patients with pDPN experienced greater clinical and economic burdens than patients with non-pDPN, suggesting that patients who develop pDPN may suffer not only from the complications of DM and pain, but also from other comorbid disorders.