Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.

INTRODUCTION: Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. METHODS: Patients aged ≥ 18 years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1 bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. RESULTS: A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs [95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. In the All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36 (0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). CONCLUSIONS: The use of bDMARDs was not a time-dependent risk factor for malignancy.

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.

OBJECTIVES: To 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 with rheumatoid arthritis (RA). METHODS: Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR. RESULTS: In 53 448 cases, IRs/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX. CONCLUSIONS: Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.

Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database.

OBJECTIVE: We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). METHODS: We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (<65, ≥65 and <75, and ≥75 years). RESULTS: Of 5506 patients, 2265 (41.1%) were <65 years, 1709 (31.0%) were 65-74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24-4.61); adalimumab, 1.90 (0.75-4.83); golimumab, 1.21 (0.66-2.23); and abatacept, 0.89 (0.49-1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11-0.85). CONCLUSION: In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.

Nationwide clinical and epidemiological study of large-vessel vasculitis in Japan in 2017.

OBJECTIVE: We conducted a nationwide epidemiological study to estimate the number of patients with Takayasu arteritis (TAK) and giant cell arteritis (GCA) in Japan and to describe the clinical characteristics of these patients. METHODS: The first survey was designed to estimate the number of patients with TAK and GCA who were treated at medical institutions in Japan in 2017. The second survey was designed to collect data on the clinical characteristics of the patients who were reported in the first survey. RESULTS: Of the 3495 institutions selected for the first survey, 1960 (56.1%) responded. The number of patients with clinically diagnosed TAK and GCA was estimated to be 5320 (95% confidence interval, 4810-5820) and 3200 (95% confidence interval, 2830-3570), respectively. Aortic regurgitation was reported in 35% of patients with TAK, and eye-related comorbidities were observed in 30.4% of patients with GCA. The common carotid and internal carotid arteries were the most frequently involved in patients with TAK (62.7%). Subclavian artery lesions and thoracic or abdominal aorta lesions were reported in 31% and 42.6% of patients with GCA, respectively. CONCLUSIONS: The number of patients with TAK and GCA was estimated simultaneously, and significant differences in clinical characteristics were observed between the two diseases.

Subjective symptoms contributing to the quality of life of rheumatoid arthritis patients with clinical remission from the IORRA database.

OBJECTIVES: To explore patient-reported outcomes (PROs) related to quality of life (QOL) in patients with rheumatoid arthritis (RA) who achieved clinical remission. METHODS: In the Institute of Rheumatology, Rheumatoid Arthritis dataset, RA patients >18 years old who met the simplified disease activity index (SDAI) remission criteria in April 2017 were enrolled in this analysis. Pain-visual analogue scale (pain-VAS) (0-100 mm), patient's global assessment of disease activity (Pt-GA; 0-100 mm), Japanese version of the Health Assessment Questionnaire, duration of morning joint stiffness, and fatigue [Checklist Individual Strength 8R (CIS)] were the tools used to evaluate PROs. To assess the contribution of each PRO to the European QOL-5 Dimensions-5 Level (EQ-5D-5L) score, an analysis of variance was conducted. RESULTS: Among the 2443 patients with remission, the mean EQ-5D-5L was 0.9. The mean pain-VAS and Pt-GA were 7.2 and 7.4, respectively. Factors that significantly contributed to the EQ-5D-5L were pain-VAS (48.8%), CIS score (18.1%), and Pt-GA (15.6%). Around 82.5% of the variance in EQ-5D-5L was explained by the three PROs. CONCLUSIONS: This study demonstrated that pain-VAS, CIS, and Pt-GA were significant contributors to the EQ-5D-5L score in patients with RA who achieved the simplified disease activity index remission criteria.

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

OBJECTIVES: To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. RESULTS: The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). CONCLUSIONS: The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.

Unincreased risk of hospitalized infection under targeted therapies versus methotrexate in elderly patients with rheumatoid arthritis: a retrospective cohort study.

BACKGROUND: Infection is one of the primary concerns during treatment for rheumatoid arthritis (RA) in elderly patients. However, infection risk of patients with RA receiving targeted therapy (TT) including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKIs) in elderly patients are scarce. The aim of this study was to compare the risk of hospitalized infection (HI) with TT versus methotrexate (MTX) therapy among young, elderly, and older elderly patients with RA. METHODS: Using Japanese claims data, patients satisfying the following criteria were enrolled: (1) ≥ one ICD10 code for RA; (2) ≥ one prescription of MTX or TT (bDMARDs and JAKIs) between April 2008 and September 2018; and (3) ≥16 years old. We calculated the incidence rate (IR) of HI per 100 patient-years in the young, elderly, and older elderly groups (those aged 16-64, 65-74, and ≥75 years, respectively) and the IR ratio (TT vs. MTX) of HI. A logistic regression model was used to estimate the associations between HI and TT versus MTX in each group. RESULTS: The overall IR of HI per 100 patient-years (95% confidence interval) was 3.2 [2.9-3.5], 5.0 [4.6-5.4], and 10.1 [9.5-10.9] in the young, elderly, and older elderly groups, respectively. Concomitant use of MTX or immunosuppressive DMARDs with TT was less frequent in the elderly and older elderly groups. The adjusted odds ratio of TT vs. MTX for HI was 1.3 (1.0-1.7; p = 0.021), 0.79 (0.61-1.0; p = 0.084), and 0.73 (0.56-0.94; p = 0.015) in the young, elderly, and older elderly groups, respectively. CONCLUSION: The overall IR of HI was increased with age. The risk of HI under TT compared to MTX was not elevated in elderly and older elderly patients after adjusting for patients' characteristics and concomitant treatments.

Association of methotrexate use and lymphoproliferative disorder in patients with rheumatoid arthritis: Results from a Japanese multi-institutional retrospective study.

OBJECTIVES: To investigate the risk factors and clinical characteristics of lymphoproliferative disorder (LPD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We enrolled patients with RA aged ≥20 years who visited the participating hospitals between April 2011 and July 2011. We investigated the risk factors for LPD using a Cox proportional hazard model and described pathological features and vital prognosis of LPD in patients with RA. RESULTS: We enrolled 9815 patients with the following characteristics at baseline: female 79.4%, median age 63 years; median disease duration 7 years; median DAS28-CRP (3) 3.1; prevalence of MTX use 60.0%. Sixty-eight patients (0.69%) developed LPD in 3-year observation period. Multivariable analysis showed that age by decade (hazard ratio [95% confidence interval], 1.47 [1.18-1.85]) and MTX use at baseline (2.35 [1.25-4.42] for ≤8 mg/week, 4.39 [2.07-9.32] for >8 mg/week versus non-use) were significant risk factors of LPD. Of 55 patients with pathological diagnosis, diffuse large B cell lymphoma was the most frequent (54%). The 5-year mortality of LPD was 24%. The major cause of death was lymphoma (81%). CONCLUSION: This nationwide study revealed risk factors, clinical characteristics, and prognosis of LPD in the largest number of Japanese patients with RA.

Geographic variations in rheumatoid arthritis treatment in Japan: A nationwide retrospective study using the national database of health insurance claims and specific health checkups of Japan.

OBJECTIVES: To characterize the treatments for rheumatoid arthritis (RA) among institution types and prefectures in Japan. METHODS: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan in the 2017 fiscal year, we investigated disease-modifying antirheumatic drug (DMARD) and oral corticosteroid prescription trends across 825 thousand RA patients. These data were compared between specialized and non-specialized institutions and by prefecture. RA specialized institutions (SIs) were defined as either institutions registered in the rheumatology training program at the Japan College of Rheumatology or institutions where board-certified rheumatologists were employed. RESULTS: The overall percentage of patients who never visited an SI was 31.8% and increased with age (16-29 years old = 15.6%; ≥80 years = 42.8%). In twelve prefectures (25.5%), the proportions of patients who never visited an SI were at least 10% higher than the overall average. The proportions of patients who only visited SIs and were prescribed methotrexate and biological DMARDs were ranged from 51.9-72.9% and 19.5-33.2%, respectively. However, those of patients who had never visited an SI and were prescribed those medications were 44.0-71.6% and 7.2-28.0%, respectively. CONCLUSIONS: This is the first study evaluating the trends in RA treatments by prefecture and institution specialty by using the NDB Japan. Opportunities of patients with RA for visiting SI was unevenly distributed in Japan, affecting some aspects of treatment provided.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Differences in patients' population and efficacy/effectiveness of biologic disease-modifying antirheumatic drugs between randomized controlled trials and real-world settings in patients with rheumatoid arthritis - using the IORRA cohort.

OBJECTIVES: To evaluate the differences in patients' population and efficacy/effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis. METHODS: We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method. RESULTS: Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30-0.51), 0.41 (0.30-0.57), 0.54 (0.35-0.82), and 1.28 (1.10-1.56), respectively. CONCLUSIONS: Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice.

Estimated medical costs of methicillin-resistant Staphylococcus aureus infection classified by polymerase chain reaction-based open reading frame typing in Japan.

This retrospective, observational cohort study investigated the economic impact of genotype by classifying methicillin-resistant Staphylococcus aureus (MRSA) by using the polymerase chain reaction-based open reading frame typing (POT) method. Using administrative claims and bacteriological data for April 2016 to March 2021 from the University of Yamanashi Hospital, we ascertained the POT1 numbers and classified MRSA as either "hospital-derived" or "community-derived". We defined MRSA-associated medical practices and estimated the associated medical costs. After applying inverse probability of treatment weighting (IPTW)-based adjustment for patient characteristics between the two groups, we estimated the differences in medical costs during the "total therapy period" (defined as the interval from specimen submission to Day 42 after the susceptibility report) and the "definitive therapy period" (defined as the interval from susceptibility reporting to Day 42). Among the 135 MRSA-infected patients, 54 and 81 were classified as having hospital-derived and community-derived MRSA infections, respectively. Significant differences in patient characteristics were observed with regard to age (p = 0.0478), sex (p = 0.0422), surgery (p = 0.0349), chemotherapy (p = 0.0457) and immunosuppressive drug use (p = 0.0222). The median duration of the definitive therapy was 29 and 27 days, and the mortality rate during this period was 11% and 5% for the hospital-derived and community-derived types, respectively. After IPTW-based adjustment, the medical costs for the total therapy period were 324,480 and 296,462 Japanese yen (JPY) per patient for the hospital-derived and community-derived types, respectively, whereas the medical costs for the definitive therapy period were 279,635 and 256,542 JPY per patient for the hospital-derived and community-derived types, respectively. No statistically significant difference was detected (p = 0.5813 and p = 0.6355, respectively). In this study, MRSA healthcare costs were compared according to the POT scores, and no statistically significant differences were observed between hospital-derived and community-derived MRSA infections.

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up.

OBJECTIVES: The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). METHODS: Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, has been reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate and adverse events. RESULTS: Fifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8-100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 vs 47.2%, P = 0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%, P = 0.007) and ES (20.3%, P = 0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (P = 0.007). CONCLUSION: SMX/TMP 200/40 mg had a high PCP prevention rate and was superior to SMX/TMP 400/80 mg in terms of drug retention and safety. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.

Prevalence of patients with rheumatoid arthritis and age-stratified trends in clinical characteristics and treatment, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

AIM: To estimate the prevalence and age-stratified treatment trends and clinical characteristics of rheumatoid arthritis (RA) in Japan. METHOD: Using 7 RA definitions, the prevalence of RA in those aged ≥16 years was estimated using the National Database of Health Insurance Claims and Specific Health Checkups of Japan in the fiscal year 2017. We analyzed age-stratified trends in characteristics and treatments. RESULTS: Of 1 116 122 patients aged ≥16 years with at least 1 RA-related International Classification of Diseases-10 code, 825.7 thousand patients (women, 76.3%) were assessed as having RA with an estimated prevalence of 0.65%. The highest age-stratified prevalence was 1.63% in patients aged 70-79 years. Overall, 60.8% and 7.0% of patients with RA were aged ≥65 years and ≥85 years, respectively. Methotrexate use was most frequent in patients aged 50-59 years (73.0%) and least frequent in patients aged ≥85 years (38.2%). Biologic disease-modifying antirheumatic drugs use was 50.9% in patients aged 16-19 years and decreased to 13.7% in those aged ≥85 years. Preference for the use of tumor necrosis factor inhibitors versus abatacept decreased from 24.0:1 to 1.7:1 in patients aged 16-19 years and ≥85 years, respectively. The prevalence of cardiovascular disease was 3.5% in patients aged 60-69 years and 12.1% in those aged ≥85 years. Overall RA-related orthopedic surgeries were most prevalent in patients aged 70-79 years. CONCLUSION: The estimated prevalence of patients with RA in Japan was 0.65%. Age-stratified treatment trends and clinical characteristics have been described in a super-aged society for the first time.

The risk of hospitalized infection in patients with systemic lupus erythematosus treated with hydroxychloroquine.

OBJECTIVE: To compare the risk of hospitalized infection (HI) between users and non-users of hydroxychloroquine (HCQ) in systemic lupus erythematosus (SLE). METHODS: Using claims data, patients were defined as SLE cases by the following criteria: 1) they had at least one SLE diagnostic code; 2) they had a prescription for specific drugs, including corticosteroids, steroid pulse therapy, and immunosuppressive drugs; and 3) they were at least 16 years old between September 2015 and July 2017 (n = 17,483). The SLE cases with at least one prescription for HCQ were defined as the HCQ group (n = 1,431), while the others were defined as the non-HCQ group. Among the SLE cases, propensity score-matched cases were observed for 1 year (n = 1,095 in each group). RESULTS: The median age and proportion of female patients in both groups were about 42 years and 88%, respectively. The proportions of cases with HIs were similar (HCQ group, 4.5%; non-HCQ group, 5.6%; p = 0.240, McNemar test). The hazard ratio of the HCQ group for HIs after adjusting for patients' characteristics was not significant at 0.9 (0.6-1.3). CONCLUSION: The use of HCQ was not associated with a risk of HIs in patients with SLE.

Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis.

BACKGROUND: Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA. METHODS: Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders (n = 27) and non-responders (n = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified "response to type I interferon (IFN)" with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders (p < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82-1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications. CONCLUSION: Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.

International descriptive study for comparison of treatment patterns in patients with knee osteoarthritis between Korea and Japan using claims data.

AIM: To compare medication prescriptions for patients with knee osteoarthritis (KOA) in the real world in Korea and Japan. METHODS: This retrospective and descriptive population-based study was conducted using claims data provided by Health Insurance Review and Assessment in Korea and JMDC Inc in Japan. We defined individuals as KOA patients if they had an International Classification of Diseases 10 (ICD10) code for gonarthrosis (M17) and were ≥50 years old in 2012. Korean and Japanese patients were matched for age and sex using frequency matching. Patients were observed for 1 year from the first month of the ICD10 code M17 in 2012. We described baseline characteristics including prevalence of comorbidities, and use of medication for KOA during the observational period. RESULTS: The median age was 59 and the percentage of women was 61.4 in both countries (N = 1 133 138 in Korea, N = 10 498 in Japan). The prevalence of nonsteroidal anti-inflammatory drug (NSAID) usage in Japan (74.7%) was significantly higher than that in Korea (59.0%). Analgesics such as acetaminophen and symptomatic slow-acting drugs for OA (SYSADOA) were significantly more frequently used in Korea (25.8%) than in Japan (9.4%). Intra-articular injection (IAI) of corticosteroids or hyaluronic acid was performed more frequently in Japanese patients (57.3%) than Korean patients (30.5%). CONCLUSIONS: Medication patterns for KOA in Korea and Japan are described for the first time. Use of NSAIDs and IAI were more common in Japan, while other pain killers and SYSADOA were more commonly prescribed in Korea.

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

AIM: 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. METHOD: 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 ≥30 mg/d, CS pulse therapy, immunosuppressive agents or rituximab during hospitalization between April 2008 and April 2017; and (c) at least 7 days 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. RESULTS: 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 10 mg (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. CONCLUSION: 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.