Safety risk associated with use of nonsteroidal anti-inflammatory drugs in Japanese elderly compared with younger patients with osteoarthritis and/or chronic low back pain: A retrospective database study.

PURPOSE: This study aimed to assess the safety risks associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) in elderly patients (≥65 years) compared with younger patients (<65 years) with osteoarthritis (OA) and/or chronic low back pain (CLBP). METHODS: A retrospective analysis was conducted on anonymized claims data of patients prescribed NSAIDs for OA and/or CLBP from 2009 to 2018 using hospital-based administrative database-Medical Data Vision (MDV). The key outcome was the incidence of developing gastrointestinal (GI), renal, and acute myocardial infarction (AMI) that are well-known events associated with NSAID use. RESULTS: Of 288,715 patients included, 23.7%, 60.5%, and 15.8% had OA, CLBP, or both, respectively. Elderly patients used non-oral NSAIDs more frequently than oral NSAIDs (57.8% and 38.7%, respectively), whereas younger patients showed comparable use (50.7% and 52.8%, respectively). The incidence of events per 10,000 person-years (95% CI) was higher in the elderly than in younger patients: GI, 29.68(27.67-31.68) vs. 16.61(14.60-18.63); renal, 124.77(120.56-128.99) vs. 39.88(36.72-43.03); and AMI, 27.41(25.48-29.35) vs. 10.90(9.27-12.53), respectively. After adjusting for covariates, the increase in risk for these events was seen in patients >70 years compared with younger patients (18-30 years) and was remarkable in patients >80 years with 2-fold, 10-fold, and 7-fold higher risk for developing GI, renal, and AMI events, respectively. CONCLUSION: Risk for developing NSAID-associated events was higher in the elderly; particularly, renal and AMI events that remarkably increased in patients >80 years. To reduce them, NSAIDs should be prescribed at the lowest effective dose for the shortest duration possible.

A Retrospective Database Study of Gastrointestinal Events and Medical Costs Associated with Nonsteroidal Anti-Inflammatory Drugs in Japanese Patients of Working Age with Osteoarthritis and Chronic Low Back Pain.

CONTEXT: The real-world burden of gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Japanese patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) remains unreported. OBJECTIVE: To assess the incidence and economic burden of NSAID-induced GI events by using data from large-scale real-world databases. METHODS: We used the Japanese Medical Data Center database to retrospectively evaluate anonymized claims data of medical insurance beneficiaries employed by middle- to large-size Japanese companies who were prescribed NSAIDs for OA and/or CLBP between 2009 and 2018. RESULTS: Overall, 180,371 patients were included in the analysis, of whom 32.9% had OA, 53.8% had CLBP, and 13.4% had both OA and CLBP. NSAIDs were administered as first-line analgesics to 161,152 (89.3%) of the patients in the sample, in oral form to 90.3% and as topical patches to 80.4%. A total of 65.1% used combined oral/topical patches. Of the 21.0% of patients consistently using NSAIDs (percentage of days supplied ≥70%), 54.5% received patches. A total of 51.5% patients used NSAIDs for >1 to ≤6 months. The incidence of GI events was 9.97 per 10,000 person-years (95% confidence interval: 8.92-11.03). The risk of developing GI events was high in elderly patients and patients with comorbidities and remained similar for patients receiving oral vs. topical NSAIDs. Longer treatment duration and consistent NSAID use increased the risk of GI events. The cost (median [interquartile range]) of medications (n = 327) was US$ 80.70 ($14.10, $201.40), that of hospitalization (n = 33) was US$ 2,035.50 ($1,517.80, $2,431.90), and that of endoscopic surgery (n = 52) was US$ 418.20 ($418.20, $418.20). CONCLUSION: NSAID-associated GI toxicity imposes a significant health and economic burden on patients with OA and/or CLBP, irrespective of whether oral or topical NSAIDs are used.

The societal burden of chronic pain in Japan: an internet survey.

OBJECTIVES: Chronic pain affects between 10-20 % of the population of Japan and several specific types of chronic pain have been found to be associated with worse health outcomes. The aim of the current study was to investigate the economic burden of chronic pain as well as the health status among Japanese patients. METHODS: Data from the Japan National Health and Wellness Survey (NHWS), a cross-sectional health survey of adults, were used (N = 30,000). Respondents with chronic pain (N = 785) were compared with respondents without chronic pain (N = 29,215) with respect to health status (using the SF-12v2), work productivity and activity impairment (WPAI questionnaire), and healthcare resource use using regression modeling, controlling for demographic and health history covariates. Indirect costs were calculated using wage rates and the human capital method. RESULTS: Back pain (72.10 %) and shoulder pain/stiffness (54.90 %) were the most prevalent pain types. Adjusting for demographic and health history differences, respondents with chronic pain reported lower health status [mental component summary (MCS): 44.26 vs. 51.14; physical component summary (PCS): 44.23 vs. 47.48; both p < 0.05], greater absenteeism (4.74 vs. 2.74 %), presenteeism (30.19 vs. 15.19 %), overall work impairment (31.70 vs. 16.82 %), indirect costs (¥ 1488,385 vs. ¥ 804,634), activity impairment (33.45 vs. 17.25 %), physician visits (9.31 vs. 4.08), emergency room (ER) visits (0.19 vs. 0.08), and hospitalizations (0.71 vs. 0.34) (all p < 0.05). Nearly 60 % of respondents with chronic pain were untreated. The mean level of pain severity in the last week was 5.26 (using a 0-11 scale); being female, being elderly, having low income, and having multiple pain types were significantly associated with greater pain severity (all p < 0.05). Regular exercise was associated with lower pain severity (p < 0.05). CONCLUSIONS: The results suggest that chronic pain has a significant association in an individual's health status, work productivity, daily activity impairment, healthcare resource use, and economic burden in Japan. Along with low treatment rates, a multidisciplinary approach may lead to an improved quality of life and reduce the economic burden among patients with chronic pain in Japan.

Factors Related to Treatment Non-Adherence Among Caregivers of Pediatric and Adolescent Growth Hormone Deficiency Patients in Japan.

Background: About one-third of caregivers of pediatric or adolescent growth hormone deficiency (pGHD) patients in Japan have reported poor treatment adherence. However, few studies have examined factors related to adherence for that group. Objective: The aim of this study is to consider factors related to poor adherence to daily treatment among caregivers of pGHD patients in Japan. Methods: A cross-sectional survey was conducted among caregivers of pGHD patients in Japan. Caregivers were asked about demographic and treatment characteristics, health literacy, treatment satisfaction, opinions about treatment, and treatment adherence. Health literacy was assessed using the 14-item health literacy scale (HLS-14). Adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Statistical association with adherence was considered using Chi-square and Student's t-testing. An exploratory factor analysis (EFA) and K-means cluster analysis was conducted to consider the influence of treatment satisfaction and opinions concerning treatment on adherence. Results: Responses were collected from 112 caregivers. The caregiver's age being 30-39 years old, the primary caregiver being male, the primary caregiver being employed, and low functional health literacy for the caregiver were associated with poor adherence. Patients being pre-elementary school age was also associated with poor adherence. Low satisfaction with drug treatment and/or their device and communication with healthcare professionals (HCPs), and lack of agreement with the importance of treatment management (eg, keeping injection records, getting informed about the disease/therapy, reporting non-adherence, and sticking to an administration schedule), were also associated with poor adherence. Conclusion: Strategies to improve treatment adherence among caregivers of pGHD patients in Japan should consider the age, gender, and employment status of the caregiver - as well as their functional literacy. Improvement in satisfaction with the drug or device used, better communication with HCPs, and greater awareness of the importance of treatment management, may also lead to better adherence.

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.

Cost-Effectiveness Analysis of the Treatment Strategies with or without Opioid Medications in Surgery-Eligible Patients with Osteoarthritis in Japan.

AIM: The aim of this study was to evaluate the cost effectiveness of treatment strategies without opioid medications (non-opioid treatment strategy) versus strategies with opioid medications (opioid treatment strategy) among surgery-eligible patients with osteoarthritis (OA) of the knee or hip in Japan. MATERIALS AND METHODS: We built a Markov cohort model to evaluate outcomes for the treatment strategies in surgery-eligible patients aged ≥ 65 years with OA of the knee or hip in Japan. The opioid treatment strategy as an intervention includes a health state with opioid medication in the treatment pathway. On the other hand, for the non-opioid treatment strategy, there is no health state with opioid medication. A targeted literature review and database analysis were conducted to identify and define the values of the variables included in the model. The time horizon was set to 30 years, and a 2% discount was applied for cost and quality-adjusted life-years (QALYs). Sensitivity analysis and scenario analysis were performed in the model. The outcomes were QALYs and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, the non-opioid treatment strategy was dominant over the opioid treatment strategy and associated with an incremental cost and QALYs of - 53,878 JPY (- 499 USD) and 0.03 QALYs, respectively, in patients with knee OA, and - 54,129 JPY (- 502 USD) and 0.02 QALYs, respectively, in patients with hip OA. One-way sensitivity analysis showed the ICER was most sensitive to the QALY for opioid monotherapy. Probabilistic sensitivity analyses showed a high degree of uncertainty associated with the results. LIMITATIONS: Study limitations included assumptions related to transition probabilities of the health states, and a lack of Japanese-specific data for transition probabilities, incidence of adverse events and utility values. CONCLUSIONS: This study suggests that the non-opioid treatment strategy is cost effective compared with the opioid treatment strategy in the management of surgery-eligible patients with OA of the knee or hip. However, this final conclusion may not be accurate as the methodology is heavily reliant on assumptions.

Efficacy, General Safety, and Joint Safety of Tanezumab in Japanese Patients with Osteoarthritis: Subgroup Analyses from Two Randomized, Phase 3 Studies.

INTRODUCTION: Tanezumab is a monoclonal antibody against nerve growth factor that is under investigation for the treatment of osteoarthritis (OA) pain. We conducted subgroup analyses of two randomized phase 3 studies to summarize efficacy, general safety, and adjudicated joint safety of tanezumab in Japanese patients with moderate-to-severe OA. METHODS: In Study 1 (NCT02528188), patients received subcutaneous tanezumab 2.5 mg or 5 mg every 8 weeks or daily oral nonsteroidal anti-inflammatory drugs (NSAID) for 56 weeks. The co-primary efficacy endpoints were change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale score and WOMAC Physical Function subscale score at Week 16 (overall study and Japan-specific endpoints) as well as Patient Global Assessment (PGA)-OA score at Week 16 (overall study endpoint only). In Study 2 (NCT02709486), patients received subcutaneous tanezumab 2.5 mg, 5 mg, or placebo every 8 weeks for 24 weeks. Safety monitoring included adjudicated composite joint safety endpoint (CJSE) including rapidly progressive osteoarthritis type 1 (RPOA1), RPOA2, primary osteonecrosis, pathological fracture, or subchondral insufficiency fracture. RESULTS: For Study 1, Japanese patients (n = 200) treated with tanezumab 2.5 mg and 5 mg showed numerically greater improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA scores versus NSAID at Week 16. Incidences of treatment-emergent adverse events were generally similar between tanezumab 2.5 mg, 5 mg, and NSAID groups. In the integrated safety analysis (Studies 1 + 2; n = 306), ten patients were adjudicated to have a component of CJSE: RPOA1 [tanezumab 2.5 mg (n = 2), tanezumab 5 mg (n = 5)], RPOA2 [tanezumab 2.5 mg (n = 1), tanezumab 5 mg (n = 1)], or primary osteonecrosis [tanezumab 2.5 mg (n = 1)]. Time-adjusted adjudicated rates of RPOA1 and RPOA2 were higher with tanezumab than NSAID or placebo and increased with dose of tanezumab. CONCLUSION: Observations from the Japanese subgroup were generally consistent with the overall study populations.

Burden of Renal Events Associated with Nonsteroidal Anti-inflammatory Drugs in Patients with Osteoarthritis and Chronic Low Back Pain: A Retrospective Database Study.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) have long-term benefits but are limited by side effects. We assessed the health and economic burden of renal events associated with NSAID use in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP). METHODS: This retrospective, large-scale, medical claims database study of Japanese patients receiving NSAIDs for OA and/or CLBP between 2009 and 2018 assessed the incidence of renal events and effect of treatment duration, mode of administration, and usage consistency of NSAIDs. RESULTS: Of 180,371 patients, NSAIDs were prescribed as first-line analgesics in 89.3%. Incidence per 10,000 person-years (95% confidence interval [CI]) for renal events was 23.46 (21.84-25.08) and for progression of chronic kidney disease (CKD) was 267.12 (189.93-344.32). Longer treatment duration (> 1 to ≤ 3 years, risk ratio [RR] 1.32, 95% CI 1.12-1.54; P = 0.0007; > 3 to ≤ 5 years, RR: 1.38, 95% CI 1.04-1.84; P = 0.0254 vs. < 1 year) and consistent use (RR: 1.24, 95% CI 0.99-1.55; P = 0.0595) increased the risk of renal events but the latter did not reach statistical significance. The risk was similar in patients using patch/oral NSAIDs and high in elderly patients and in those with diabetes, hypertension, and other cardiovascular disease. Following a renal event, median 1-year cost of drug treatment was $27.90; hospitalization, $1779.40; and dialysis, $33,018.40. CONCLUSIONS: Risk of renal events significantly increased with prolonged and consistent NSAID use (irrespective of mode of administration), with age, and in patients with certain comorbidities. Careful NSAID use is recommended in patients with CKD and those at high risk for CKD.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) for pain relief but their use is limited by side effects. These side effects may include abdominal, heart, and kidney problems. This article presents the results from a large claims database study in Japan that assessed the incidence of renal events and the associated healthcare cost. Impact of NSAIDs treatment duration, mode of administration, and usage consistency on the risk of developing renal events was evaluated. Results showed high incidence of renal events and progression of chronic kidney disease. Longer treatment duration and consistent use increased the risk of developing renal events. The risk was similar in patients using patch/oral NSAIDs and high in elderly patients and those with diabetes, hypertension, and other heart diseases. The estimated cost of drug treatment, hospitalization, and dialysis was also high. The author of the study would recommend NSAIDs to be used carefully in patients at risk for (or with) chronic kidney disease.

Database Analysis on the Relationships Between Nonsteroidal Anti-inflammatory Drug Treatment Variables and Incidence of Acute Myocardial Infarction in Japanese Patients with Osteoarthritis and Chronic Low Back Pain.

INTRODUCTION: We aimed to analyze the relationships between nonsteroidal anti-inflammatory drug (NSAID) treatment variables and the incidence of acute myocardial infarction (AMI) in Japanese patients with osteoarthritis (OA) and chronic low back pain (CLBP) using the data from a large-scale, real-world database. METHODS: We retrospectively analyzed anonymized claims data from the Japanese Medical Data Center of medical insurance beneficiaries who were prescribed NSAIDs for OA and/or CLBP from 2009 to 2018. RESULTS: Of 180,371 patients, 89.3% received NSAIDs as first-line analgesics (oral, 90.3%; patch, 80.4%; other transdermal drugs, 24.0%). Incidence of AMI was 10.27 per 10,000 person-years (95% confidence interval 9.20-11.34) in the entire study population. There was a trend towards increased risk in patients using NSAIDs for more than 5 years (P = 0.0784) than in those using NSAIDs for less than 1 year. Risk of AMI significantly increased with age and comorbidities of diabetes and cardiovascular disease (CVD). The risk for AMI was similar for patients who consistently used NSAIDs compared to those using them intermittently and patients who used patch compared to oral NSAIDs. Elderly patients used NSAIDs more consistently and used NSAID patches more frequently. CONCLUSION: In Japanese patients with OA and CLBP, we saw a trend of increased risk for AMI in patients using NSAIDs for more than 5 years. Elderly patients had a higher prevalence of diabetes, hypertension, and other CVD which increased the risk of AMI. Although NSAID patches were preferred to oral NSAIDs in elderly patients, risk for AMI was similar between the two modalities. Therefore, we suggest using NSAIDs carefully, especially in elderly patients and those at risk of developing CVD.

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.

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.

Patterns of drug treatment in patients with osteoarthritis and chronic low back pain in Japan: a retrospective database study.

Purpose: Musculoskeletal diseases, including osteoarthritis (OA) and low back pain (LBP), are the leading causes of years lived with disability, and are associated with lowered quality-of-life, lost productivity, and increased healthcare costs. However, information publicly available regarding the Japanese real-world usage of prescription medications is limited. This study aimed to describe the clinical characteristics of patients with OA and chronic LBP (CLBP), and to investigate the patterns of medications and opioid use in Japanese real-world settings. Materials and methods: A retrospective study was conducted using a Japanese administrative claims database between 2013 and 2017. The outcomes were patient characteristics and prescription medications, and they were evaluated separately for OA and CLBP. Results: The mean age of 118,996 patients with OA and 256,402 patients with CLBP was 68.8±13.1 years and 64.8±16.4 years, respectively. Approximately 90% of patients with OA and CLBP were prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Other prescriptions included hyaluronate injection (35.6%), acetaminophen (21.4%), and steroid injection (20.0%) in patients with OA, and pregabalin (39.0%) and acetaminophen (22.4%) in patients with CLBP. Weak opioids were prescribed to 10.7% and 20.6% of patients with OA and CLBP, respectively. The prescription of COX-2 inhibitors (OA: +6.5%; CLBP: +6.7%) and acetaminophen (OA: +16.4%; CLBP: +14.4%) increased between 2013 and 2017. The first commonly prescribed medication among patients with OA and CLBP were NSAIDs; hyaluronate injection (patients with OA) and pregabalin (patients with CLBP) were also common first-line medications. Acetaminophen, steroid injection (patients with OA), and weak opioids were prescribed more in the later phases of treatment. Conclusion: Most patients were prescribed limited classes of pain drugs, with NSAIDs being the most common pain medication in Japan for patients with OA and CLBP. Opioid prescription was uncommon, and were weak opioids when prescribed.

Treatment patterns of postherpetic neuralgia patients before and after the launch of pregabalin and its effect on medical costs: Analysis of Japanese claims data provided by Japan Medical Data Center.

Except for neurotrophin, no drug had an indication for postherpetic neuralgia (PHN) in Japan prior to pregabalin approval. This approval might have changed PHN treatment patterns. This study aimed to compare PHN treatment patterns and medical costs between patients who started treatment before and after pregabalin approval. Japanese claims data were used to identify patients aged 18 years or more with PHN, postherpetic trigeminal neuralgia or postherpetic polyneuropathy who were initiated on their first PHN-associated prescription through May 2010 (before approval) or from June 2010 (after approval). From these claims, 6-month treatment patterns from first prescription were compared for the periods before and after approval. These patterns included pain-related medications and the frequency of pain-relief procedures. All-cause and pain-related medical costs were also compared for these periods. The number of PHN patients who were initiated on treatment before and after approval were 107 (mean age, 47.4 ± 13.0 years) and 505 (45.9 ± 13.0), respectively. Post-approval, significant reductions were observed for prescription of non-steroidal anti-inflammatory drugs, tricyclic antidepressants and neurotrophin relative to before approval. Excluding pregabalin acquisition costs, mean costs per patient for medications associated with PHN for 6 months from the first prescription were significantly lower after approval, ¥2882 vs ¥4185. Total medical costs were similar in both periods. Approval of pregabalin appeared to result in a treatment paradigm toward use of an approved therapy with demonstrated efficacy.

Humanistic and economic burden of fibromyalgia in Japan.

PURPOSE: The aim of this study was to examine the health and economic burden associated with fibromyalgia among adults in Japan. MATERIALS AND METHODS: Data from the 2011-2014 Japan National Health and Wellness Survey (n=115,271), a nationally representative survey of adults, were analyzed. The greedy matching algorithm was used to match the respondents who self-reported a diagnosis of fibromyalgia with those not having fibromyalgia (n=256). Generalized linear models, controlling for covariates (eg, age and sex), examined whether the respondents with fibromyalgia differed from matched controls based on health status (health utilities; Mental and Physical Component Summary scores from Medical Outcomes Study: 12-item Version 2 and 36-item Version 2 Short Form Survey), sleep quality (ie, sleep difficulty symptoms), work productivity (Work Productivity and Activity Impairment Questionnaire - General Health Version 2.0), health care resource use, and estimated annual indirect and direct costs (based on published annual wages and resource use events) in Japanese yen (¥). RESULTS: After adjustment for covariates, respondents with fibromyalgia relative to matched controls scored significantly lower on health utilities (adjusted means =0.547 vs 0.732), Mental Component Summary score (33.15 vs 45.88), and Physical Component Summary score (39.22 vs 50.81), all with P<0.001; these differences exceeded the clinically meaningful levels. In addition, those with fibromyalgia reported significantly poorer sleep quality than those without fibromyalgia. Respondents with fibromyalgia compared with those without fibromyalgia experienced significantly more loss in work productivity and health care resource use, resulting in those with fibromyalgia incurring indirect costs that were more than twice as high (adjusted means =¥2,826,395 vs ¥1,201,547) and direct costs that were nearly six times as high (¥1,941,118 vs ¥335,140), both with P<0.001. CONCLUSION: Japanese adults with fibromyalgia experienced significantly poorer health-related quality of life and greater loss in work productivity and health care use than those without fibromyalgia, resulting in significantly higher costs. Improving the rates of diagnosis and treatment for this chronic pain condition may be helpful in addressing this considerable humanistic and economic burden.

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.

Cost-effectiveness analysis of pregabalin for treatment of chronic low back pain in patients with accompanying lower limb pain (neuropathic component) in Japan.

OBJECTIVE: To assess the cost-effectiveness of pregabalin for the treatment of chronic low back pain with accompanying neuropathic pain (CLBP-NeP) from the health care payer and societal perspectives. METHODS: The cost-effectiveness of pregabalin versus usual care for treatment of CLBP-NeP was evaluated over a 12-month time horizon using the incremental cost-effectiveness ratio (ICER). Quality-adjusted life years (QALYs), derived from the five-dimension, five-level EuroQol (EQ-5D-5L) questionnaire, was the measure of effectiveness. Medical costs and productivity losses were both calculated. Expected costs and outcomes were estimated via cohort simulation using a state-transition model, which mimics pain state transitions among mild, moderate, and severe pain. Distributions of pain severity were obtained from an 8-week noninterventional study. Health care resource consumption for estimation of direct medical costs for pain severity levels was derived from a physician survey. The ICER per additional QALY gained was calculated and sensitivity analyses were performed to evaluate the robustness of the assumptions across a range of values. RESULTS: Direct medical costs and hospitalization costs were both lower in the pregabalin arm compared with usual care. The estimated ICERs in the base case scenarios were approximately ¥2,025,000 and ¥1,435,000 per QALY gained with pregabalin from the payer and societal perspectives, respectively; the latter included indirect costs related to lost productivity. Sensitivity analyses using alternate values for postsurgical pain scores (0 and 5), initial pain severity levels (either all moderate or all severe), and the actual EQ-5D-5L scores from the noninterventional study showed robustness of results, with ICERs that were similar to the base case. Development of a cost-effectiveness acceptability curve showed high probability (≥75%) of pregabalin being cost-effective. CONCLUSION: Using data and assumptions from routine clinical practice, pregabalin is cost-effective for the treatment of CLBP-NeP in Japan.

Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component): a non-interventional study in Japan.

OBJECTIVE: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP) under routine clinical practice. METHODS: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years) with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain). Treatment was 8 weeks with pregabalin (n=157) or usual care alone (n=174); choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep). Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale), function (Roland-Morris Disability Questionnaire), and quality of life (EuroQol 5D-5L); global assessments of change were evaluated from the clinician and patient perspectives at the final visit. RESULTS: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation) pain score, 6.3 (1.2) versus 5.8 (1.1) (P<0.001). For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of -1.3 versus -0.4 for usual care (P<0.001); pregabalin also resulted in greater PRSIS improvement at week 4 (P=0.012). Relative to usual care at week 8, pregabalin improved pain and function (both P<0.001), and showed global improvements since beginning study medication (P<0.001). Pregabalin was well tolerated. CONCLUSION: In clinical practice in patients with CLBP-NeP, pregabalin showed significantly greater improvements in pain-related interference with sleep relative to usual care. In addition, pregabalin significantly improved pain, function, and health status, suggesting the benefits of pregabalin for overall health and well-being relative to usual care in these patients. (Clinicaltrials. gov identifier NCT02273908).