Japanese Health Insurance Database Research Articles

Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database

ObjectivesTo compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients...

Importance of Regular Examination and Follow-up in Pediatric Patients with Neurogenic Bladder: 24-Month Follow-up Study Using a Japanese Health Insurance Database.

Data on the long-term management of neurogenic bladder (NGB) are scarce. We evaluated the current status of NGB management in Japanese children over 24-month follow-up using the JMDC database. In this descriptive, observational, retrospective cohort study, patients (≤ 17years) with NGB were included. Patient characteristics and their management status were investigated. A multivariate analysis evaluating the potential risk factors for the development of urinary tract infection (UTI) was performed. The diagnosis of spina bifida, demographics, baseline comorbidities, and early use of clean intermittent catheterization (CIC) and/or overactive bladder (OAB) drugs were used as independent variables. Of 883 eligible children, 39.3% had spina bifida. Over 12/24-month post-index periods, renal urinary tract ultrasound and urinalysis were performed at least once in > 35%/> 45% patients, respectively, while specific tests (urodynamics, cystourethrography, scintigraphy) were performed in substantially fewer (< 11%/< 13%) patients. Over 24months, 21.5% patients used OAB medications (mostly anticholinergics) and 10.8% underwent CIC, alone or with medications; 1.2% patients underwent surgery. Lower UTI (23.3%), urinary incontinence (9.7%), and hydronephrosis (7.0%) were the most common incident complications. Multivariate analysis evaluating risk factors for UTI showed significantly higher odds ratios with point estimates of ≥ 2 for CIC (5.70), presence of spina bifida (2.86), and constipation (2.07). Overall, urodynamic assessments were inadequately performed. Patients with use of CIC and/or having spina bifida and constipation had a higher risk of UTI, suggesting the need for careful follow-up. More guideline-compliant and diligent patient management is necessary in Japanese children with NGB.

Diseases prevalent before major depressive disorder diagnosis: an exploratory nested case–control study using health insurance-based claims data

ObjectivesMajor depressive disorder (MDD) is often comorbid with other chronic and/or serious diseases. However, little is known about the prevalence of various diseases that are present before MDD onset. We...

Urate-lowering therapy for gout and asymptomatic hyperuricemia in the pediatric population: a cross-sectional study of a Japanese health insurance database

BackgroundOur previous research showed that uric acid lowering therapy (ULT) for gout and hyperuricemia is being prescribed for pediatric patients even though these drugs have not been approved for use in children. However, the actual clinical situation has not been clearly elucidated. In this paper, we provide an in-depth look at the details of actual clinical practice.MethodsThis retrospective cross-sectional study accessed health insurance data for 696,277 children from April 2016 through March 2017 to identify pediatric patients with gout or asymptomatic hyperuricemia, calculate the proportion of patients prescribed ULTs, and analyze population characteristics. Adherence and mean dose for febuxostat and allopurinol, the most commonly prescribed drugs, were also analyzed.ResultsAmong children with gout or asymptomatic hyperuricemia, we found that 35.1% (97/276) were prescribed ULT. This proportion increased with age, especially among males. By comorbidity, ULT was prescribed to 47.9% (46/96) of patients with kidney disease, 41.3% (26/63) for cardiovascular disease, 40.0% (6/15) for Down syndrome, and 27.1% (32/118) for metabolic syndrome. In patients with kidney disease, febuxostat was prescribed more than twice as frequently as allopurinol (28 vs. 12). Median values for the medication possession ratio (MPR) of febuxostat and allopurinol were 70.1 and 76.7%, respectively, and prescriptions were continued for a relatively long period for both drugs. Both drugs were prescribed at about half the adult dose for patients 6–11 years old and about the same as the adult dose for patients 12–18 years old.ConclusionsThis study showed that the continuous management of serum uric acid is being explored using off-label use of ULT in pediatric patients with gout or asymptomatic hyperuricemia in Japan. Drug selection is based on patient characteristics such as sex, age, and comorbidities, and pediatric dosage is based on usage experience in adults. To develop appropriate pediatric ULT, clinical trials are needed on the efficacy and safety of ULT in the pediatric population.Trial registrationUMIN000036029.

Trends in actual medication use for child-onset systemic lupus erythematosus using the Japanese health insurance database 2009-18.

Immunosuppressive therapy is the mainstay of treatment for child-onset systemic lupus erythematosus (cSLE). Since epidemiological data on Japanese cSLE patients are not available, we evaluated the trends in how treatment choices have changed over time in Japan. Using the Japanese health insurance database provided by Medical Data Vision Co., Ltd, we identified cSLE patients and evaluated changes in the use of corticosteroids and immunosuppressive medications and maximum daily doses of prednisolone from 2009 to 2018. Of 182 cSLE patients, 86% were female, and the median age was 14 years. Oral prednisolone was used in more than 97% of cSLE patients during the study period, and the median of the maximum daily dose in each patient decreased over time. Intravenous cyclophosphamide was used less frequently after 2016, while mycophenolate mofetil and hydroxychloroquine were used frequently after 2016. The use of mizoribine reduced after 2014, whereas the other immunosuppressive medications showed no significant change over time; the use of biological agents was very limited. Oral prednisolone was the mainstay of treatment for cSLE, and the maximum daily dose has reduced over the past decade. The most frequently prescribed immunosuppressive therapy has shifted to mycophenolate mofetil over time.

Comprehensive Exploration of Medications That Affect the Bleeding Risk of Oral Anticoagulant Users.

Oral anticoagulants (OACs) pose a major bleeding risk, which may be increased or decreased by concomitant medications. To explore medications that affect the bleeding risk of OACs, we conducted a nested case-control study including 554 bleeding cases (warfarin, n = 327; direct OACs [DOACs], n = 227) and 1337 non-bleeding controls (warfarin, n = 814; DOACs, n = 523), using a Japanese health insurance database from January 2005 to June 2017. Major bleeding risk associated with exposure to concomitant medications within 30 d of the event/index date was evaluated, and adjusted odds ratios (aORs) were calculated using logistic regression analysis. Several antihypertensive drugs, such as amlodipine and bisoprolol, were associated with a decreased risk of bleeding (warfarin + amlodipine [aOR, 0.64; 95% confidence interval (CI): 0.41-0.98], DOACs + bisoprolol [aOR, 0.51; 95% CI, 0.33-0.80]). As hypertension is considered a significant risk factor for intracranial bleeding in antithrombotic therapy, antihypertensive drugs may suppress intracranial bleeding. In contrast, telmisartan, a widely used antihypertensive drug, was associated with an increased risk of bleeding [DOACs + telmisartan (aOR, 4.87; 95% CI, 1.84-12.91)]. Since telmisartan is an inhibitor of P-glycoprotein (P-gp), the elimination of rivaroxaban and apixaban, which are substrates of P-gp, is hindered, resulting in increased blood levels of both drugs, thereby increasing the risk of hemorrhage. In conclusion, antihypertensive drugs may improve the safety of OACs, and the pharmacokinetic-based drug interactions of DOACs must be considered.

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

BackgroundJapanese 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.ObjectiveThe 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 MethodsThis 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.ResultsAmong 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.ConclusionsThese 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00231-0.

Does Last Year's Cost Predict the Present Cost? An Application of Machine Leaning for the Japanese Area-Basis Public Health Insurance Database.

The increasing healthcare cost imposes a large economic burden for the Japanese government. Predicting the healthcare cost may be a useful tool for policy making. A database of the area-basis public health insurance of one city was analyzed to predict the medical healthcare cost by the dental healthcare cost with a machine learning strategy. The 30,340 subjects who had continued registration of the area-basis public health insurance of Ebina city during April 2017 to September 2018 were analyzed. The sum of the healthcare cost was JPY 13,548,831,930. The per capita healthcare cost was JPY 446,567. The proportion of medical healthcare cost, medication cost, and dental healthcare cost was 78%, 15%, and 7%, respectively. By the results of the neural network model, the medical healthcare cost proportionally depended on the medical healthcare cost of the previous year. The dental healthcare cost of the previous year had a reducing effect on the medical healthcare cost. However, the effect was very small. Oral health may be a risk for chronic diseases. However, when evaluated by the healthcare cost, its effect was very small during the observation period.

Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment: A Propensity Score Matching Analysis Using a Japanese Employment-Based Health Insurance Database.

PurposeThe aim of this study was to examine whether there is a difference in the risk of rehospitalization when antipsychotics are classified into two groups treated using drugs with a higher or lower affinity to H1 or α1 receptors than to D2 receptors (histamine H1 receptors, adrenaline α1 receptors [HA] high- and HA low-affinity drug group, respectively) based on affinity to receptors related to sedation using a nationwide insurance claims database in Japan.Patients and MethodsWe identified eligible patients by the following two criteria: (i) hospitalization due to schizophrenia (International Classification of Disease [ICD]-10 code: F20 or F25) in psychiatric wards between January 1st, 2005 and August 31st, 2017, and (ii) administration of HA high- or HA low-affinity drugs in the next month after discharge from the earliest hospitalization due to schizophrenia (index month). The primary endpoint was rehospitalization due to schizophrenia. The secondary endpoints were (i) involuntary rehospitalization, (ii) concomitant use of anxiolytics/hypnotics, mood stabilizers, and antiparkinsonian drugs, (iii) all-cause death, and (iv) medication discontinuation. Propensity score (PS) matching analysis was applied, and the hazard ratio (HR) of the event rate in the HA high-affinity drug group relative to the HA low-affinity drug group was calculated using Cox’s proportional hazards model.ResultsTwo thousand nine hundred and forty patients were identified as eligible patients. Among PS-matched patients (819 in each group), the HR in the HA high-affinity drug group compared with the HA low-affinity drug group was 1.018 (0.822–1.260, P = 0.870). Other outcomes did not differ significantly between the two groups.ConclusionNo significant difference was observed in the rehospitalization risk due to schizophrenia associated with HA high-affinity antipsychotic drugs. Although this study was a retrospective PS-matched cohort study, the possibility of masking of the rehospitalization risk cannot be excluded because more than 80% of the patients were administered an anxiolytic/hypnotic at the time of admission.

Treatment of Major Depressive Disorder in Japanese Patients with Cancer: A Matched Cohort Study Using Employer-Based Health Insurance Claims Data.

Background and ObjectivePatients with cancer are at high risk of major depressive disorder (MDD), but little is known about their MDD treatment. We investigated the use of antidepressants and other drugs for MDD after cancer diagnosis, and patient characteristics associated with their use.MethodsAdults with a new cancer diagnosis were matched to cancer-free patients using a Japanese employee health insurance database (JMDC); this exploratory analysis included only cohort patients diagnosed with MDD between 6 months before and 12 months after the cancer diagnosis index month. Initial prescription frequencies of antidepressants and other MDD medications were compared between cancer and cancer-free groups and analyzed according to age, sex, and hospital characteristics.ResultsCompared with the cancer-free group (n = 4097), significantly fewer patients in the cancer group (n = 1199) were prescribed antidepressants {622 (51.9%) [95% CI 49.0–54.7] vs 2385 (58.2%) [95% CI 56.7–59.7]}, particularly selective serotonin reuptake inhibitors. In contrast, prescription of other medications, especially antipsychotics and anxiolytics (tandospirone, hydroxyzine), was more frequent in the cancer group than in the cancer-free group. In the cancer group, women were prescribed antidepressants (mostly selective serotonin reuptake inhibitors) and other medications (mostly benzodiazepines) more than men. Antidepressant prescription decreased with age; patients aged < 40 years had the highest selective serotonin reuptake inhibitor and the lowest conventional antidepressant prescription rate compared with patients aged 40–64 years and ≥ 65 years. Lower selective serotonin reuptake inhibitor and benzodiazepine prescription rates were seen in large (≥ 100 beds) hospitals and in hospitals where patients received their cancer diagnosis.ConclusionsThese results suggest Japanese patients with cancer may be undertreated for MDD compared with cancer-free patients. However, when prescribed, medications may be chosen according to patient needs, including avoiding adverse effects and drug–drug interactions.Electronic supplementary materialThe online version of this article (10.1007/s40261-020-00976-6) contains supplementary material, which is available to authorized users.

Prevalence of gout and asymptomatic hyperuricemia in the pediatric population: a cross-sectional study of a Japanese health insurance database

BackgroundAlthough gout is rare in children, chronic sustained hyperuricemia can lead to monosodium urate deposits progressing to gout, just as in adults. This study assessed prevalence and characteristics of gout and asymptomatic hyperuricemia, and incidence of gouty arthritis in the pediatric population, using data from Japanese health insurance claims. The diagnosis and treatment of pediatric gout and hyperuricemia were analyzed, and specific characteristics of those patients were assessed. Since Japanese guidelines recommend treatment with uric acid lowering drugs for asymptomatic hyperuricemia as well as for gout, these data were also used to investigate the real-world use of uric acid lowering drugs in a pediatric population.MethodsThis cross-sectional study was based on a 2016–2017 Japanese health insurance claims database, one of the largest epidemiology claims databases available in Japan, which included 356,790 males and 339,487 females 0–18 years of age. Outcomes were measured for prevalence, patient characteristics, treatment with uric acid lowering drugs for gout and asymptomatic hyperuricemia, and prevalence and incidence of gouty arthritis. Because uric acid can be elevated by some forms of chemotherapy, data from patients under treatment for malignancies were excluded from consideration.ResultsTotal prevalence of gout and asymptomatic hyperuricemia in 0–18 year-olds was 0.040% (276/696,277 patients), with gout prevalence at 0.007% (48/696,277) and asymptomatic hyperuricemia at 0.033% (228/696,277). Prevalence of gout and asymptomatic hyperuricemia was highest in adolescent males, at 0.135% (176/130,823). The most common comorbidities for gout and asymptomatic hyperuricemia were metabolic syndrome at 42.8% (118/276) and kidney disease at 34.8% (96/276). Of the patients diagnosed with gout or asymptomatic hyperuricemia, 35.1% (97/276) were treated with uric acid lowering drugs. Gouty arthritis developed in 43.8% (21/48) of gout patients during the study, at an incidence of 0.65 flares/person-year.ConclusionsEven the pediatric population could be affected by asymptomatic hyperuricemia, gout, and gouty arthritis, and uric acid lowering drugs are being used in this population even though those drugs have not been approved for pediatric indications. Such off-label use may indicate a potential need for therapeutic agents in this population.Trial registrationUMIN000036029.

A Retrospective, Cross-Sectional Study on the Prevalence of Hyperuricemia Using a Japanese Healthcare Database.

This study aims to evaluate the prevalence of hyperuricemia (HU) considering both serum uric acid (SUA) levels and medication status of urate-lowering drugs (ULDs), and the association between HU and its comorbidities using a Japanese healthcare database. The study population consisted of 60,828 subjects who had at least one serum uric acid measurement between the fiscal years (FYs) 2010 and 2014 in a Japanese employment-based health insurance database (MinaCare Co., Ltd., Tokyo, Japan), which includes mutually linked medical/pharmaceutical claims data and health check-up data. Hyperuricemia was defined as a SUA level >7.0 mg/dL of the health check-up data and/or a prescription for a ULD. The association between HU and comorbidities were analyzed by comparing the prevalence of HU of each subgroup defined by presence or absence of comorbidity. The prevalence of HU in FY 2014 was 26.8% [95% confidence interval (CI): 26.2 to 27.3%] in male subjects and 0.9% (95% CI: 0.7 to 1.0%) in female subjects. According to the analyses by sex and age, a trend of increasing prevalence with age was observed in both males and females. The prevalence of HU remained stable both in males and females from FYs 2010 to 2014. The positive association between HU and well-known comorbidities were confirmed with the exception of diabetes mellitus and smoking status in male subjects. Our results provided a more accurate prevalence of HU in Japanese population. It is important to increase the awareness on HU in the society to reduce the burden of HU-related diseases.

Risk of opportunistic infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis, using a Japanese health insurance database.

Opportunistic infections (OIs) adversely affect outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to identify the incidence proportion of risk factors for OIs in patients with AAV who were on remission-induction therapy, using a Japanese health insurance database. This retrospective longitudinal population-based study was conducted using claims data provided by Medical Data Vision Co., Ltd. We defined individuals as AAV cases receiving remission-induction therapy if they met all of the following criteria: (a) having OIs with at least 1 specified International Statistical Classification of Diseases and Related Health Problems, 10th Revision code (M300, M301, M313, or M318); (b) receiving at least 1 prescription of oral corticosteroids (CS) with prednisolone (PSL)-equivalent dosage ≥30mg/d, CS pulse therapy, immunosuppressive agents or rituximab during hospitalization between April 2008 and April 2017; and (c) at least 7days of hospitalization while on the above-mentioned therapies. We calculated incidence and proportion of OIs during the year following remission-induction therapy and the adjusted odds ratio (OR) using a logistic regression model. We included 2299 patients with AAV in this study. OIs occurred in 460 patients (20.0%), with the most frequently occurring OI being cytomegalovirus infection (n=122, 6.5%). After adjusting for covariates, age by decade (OR 1.24, 95% CI: 1.12-1.36), daily PSL dose per 10mg (OR 1.16, 95% CI: 1.08-1.25), and CS pulse therapy (OR 1.29, 95% CI: 1.04-1.60) were found to be significantly associated with occurrence of OIs. Older age and corticosteroid use were found to be significant risk factors for OIs in patients with AAV on remission-induction therapy, using a health insurance database.

Higher risk of hospitalized infection, cardiovascular disease, and fracture in patients with rheumatoid arthritis determined using the Japanese health insurance database

Objective: To evaluate the risk of hospitalized infection (HI), cardiovascular disease (CVD), stroke, and fracture in rheumatoid arthritis (RA) patients compared with non-RA patients using the Japanese health insurance database.Method: Among individuals aged ≥18 years, RA cases were defined to have one RA diagnostic code and receiving ≥1 disease-modifying antirheumatic drug between 2005 and 2013 (n = 6,712). Age-, sex-, calendar year of the observation start-, and observation length-matched non-RA cases were selected at 1:5 (n = 33,560). Hazard ratios (HRs) were calculated using the time-dependent Cox regression analysis.Results: Median age of the patients was 52.0 years. The incidence rates of HI, CVD, and fracture in the RA group were 2.42/100 person-years (PY), 4.94/1,000 PY, and 10.59/1,000 PY. The crude incidence rate ratios (95% CI) (RA vs. non-RA) for HI, CVD, and fracture were 2.47 (2.20–2.77), 1.89 (1.49–2.41), and 3.35 (2.80–4.02). The adjusted HR (95% CI) (RA vs. non-RA) was significantly elevated (HI, 1.74 [1.52–1.99], CVD, 1.38 [1.04–1.85], and fracture, 1.88 (1.54–2.31)].Conclusion: The relatively young RA population had significantly higher risks of these complications than the non-RA, indicating importance of prevention of them even at young ages in clinical settings.

High prevalence of cardiovascular comorbidities in patients with rheumatoid arthritis from a population-based cross-sectional study of a Japanese health insurance database

Objective: To reveal any association between rheumatoid arthritis (RA) and cardiovascular comorbidities using a Japanese health insurance database.Method: This population-based cross-sectional study was conducted using health insurance data provided by the Japan Medical Data Center Co., Ltd. We identified 2762 RA subjects having RA diagnostic codes (ICD10 codes; M05, M060, M062–63, M068–069) with at least two physician visits more than two months apart between June 2011 and May 2012 (RA group, n = 2762). We selected age- (±5 years), sex-, and study period-matched non-RA subjects (non-RA group, n = 27,620). We compared the prevalence of cardiovascular and related comorbidities (ischemic heart diseases [IHD], cerebral infarction, hypertension [HT], dyslipidemia [DL], and diabetes mellitus [DM]) between these groups and investigated the association between RA and cardiovascular comorbidities using a conditional logistic regression analysis.Results: The prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group. Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 2.0 [1.5–2.5] and 3.1 [2.2–4.2] respectively, after adjusting for HT, DL, and DM.Conclusions: This study revealed for the first time in the Japanese population that RA was significantly associated with cardiovascular comorbidities.

FRI0088 Prevalence of Comorbidities in Patients with Rheumatoid Arthritis Using Japanese Health Insurance Database

BackgroundThe high prevalence or risk of comorbidities in patients with rheumatoid arthritis (RA) has been reported1,2. It is essential for rheumatologists to manage comorbidities appropriately since they influence on prognosis...