Establishment of the MID-NET® medical information database network as a reliable and valuable database for drug safety assessments in Japan.

PURPOSE: To establish a new medical information database network (designated MID-NET® ) to provide real-world data for drug safety assessments in Japan. METHODS: This network was designed and developed by the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency in collaboration with 23 hospitals from 10 healthcare organizations across Japan. MID-NET® is a distributed and closed network system that connects all collaborative organizations through a central data center. A wide variety of data are available for analyses, including clinical and administrative information. Several coding standards are used to standardize the data stored in MID-NET® to allow the integration of information originating from different hospitals. A rigorous and consistent quality management system was implemented to ensure that MID-NET® data are of high quality and meet Japanese regulatory standards (good post-marketing study practice and related guidelines). RESULTS: MID-NET® was successfully established as a reliable and valuable medical information database and was officially launched in April 2018. High data quality with almost 100% consistency was confirmed between original data in hospitals and the data stored in MID-NET® . A major advantage is that approximately 260 clinical laboratory test results are available for analysis. CONCLUSIONS: MID-NET® is expected to be a major data source for drug safety assessments in Japan. Experiences and best practices established in MID-NET® may provide a model for the future development of similar database networks.

No increased risk of herpes zoster in TNF inhibitor and non-TNF inhibitor users with rheumatoid arthritis: epidemiological study using the Japanese health insurance database.

OBJECTIVE: It is controversial whether the use of biological disease-modifying antirheumatic drugs (DMARDs) increases the risk of herpes zoster (HZ). We aimed to evaluate the risks of HZ in tumor necrosis factor inhibitor (TNFI) and non-TNFI users with rheumatoid arthritis (RA) over 3 years in Japan. METHOD: Using the Japanese health insurance database, we assigned patients with at least one RA diagnostic code and one prescription for any DMARDs (RA cases) recorded between January 2005 and December 2013 to the RA group. We randomly selected five age-, sex-, calendar year- and observation length-matched non-RA cases for each RA case (non-RA group), and assessed associations between RA and HZ. To evaluate the risks of HZ in TNFI and non-TNFI users, we conducted a nested case-control study (NCC) in the RA group. RESULTS: The RA group (n = 6712) had a significantly higher crude incidence rate of HZ than the non-RA group (n = 33 560) (14.2 vs. 8.3/1000 patient-years), and the adjusted odds ratio (95% confidence interval) of the RA versus non-RA groups was 1.43 (1.17-1.75). The NCC demonstrated that use of TNFI, non-TNFI, methotrexate, or immunosuppressive DMARDs did not increase the risks of HZ. Use of corticosteroid ≥ 5 mg/day conveyed a significant risk of HZ in patients with RA. CONCLUSIONS: Rheumatoid arthritis was significantly associated with the development of HZ, and use of corticosteroids ≥ 5 mg/day was identified as a significant risk factor, whereas either TNFI or non-TNFI use were not.

Association Between Medications and Herpes Zoster in Japanese Patients with Rheumatoid Arthritis: A 5-year Prospective Cohort Study.

OBJECTIVE: To investigate the association between medications and herpes zoster (HZ) in patients with rheumatoid arthritis (RA) given biological disease-modifying antirheumatic drugs (bDMARD) or conventional synthetic DMARD in the clinical setting during 5 years using the Registry of Japanese Rheumatoid Arthritis Patients on Biologics for Longterm Safety (REAL) database. METHODS: We calculated the crude incidence rate (IR) of HZ treated with systemic antiviral medications in 1987 patients from the REAL database. To estimate the association between HZ and medications, a nested case control study was performed with 1:5 case-control pairs matched for age, sex, observation start year, and comorbidity (HZ case group, n = 43; control group, n = 214). We calculated OR and 95% CI of the use of bDMARD, methotrexate (MTX), and corticosteroids for the occurrence of HZ using a conditional logistic regression analysis. RESULTS: The median patient age was 60.0 years, female proportion was 81.5%, and median disease duration was 6.0 years. The crude IR (95% CI) of HZ was 6.66 (4.92-8.83)/1000 person-years. The OR (95% CI) of medication use were 2.28 (1.09-4.76) for tumor necrosis factor inhibitor (TNFi) and 1.13 (1.03-1.23) for oral corticosteroids dosage (per 1 mg prednisolone increment), both of which were significantly elevated. The OR of non-TNFi and MTX usage were not elevated. CONCLUSION: TNFi use and higher corticosteroids dosage were significantly associated with HZ in Japanese patients with RA in the clinical setting.

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.