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Objectives: Urate-lowering efficacy and safety of febuxostat was evaluated in paediatric patients with hyperuricaemia including gout., Methods: A Phase 2 study of febuxostat in paediatric patients aged 6-18 years with hyperuricaemia including gout was conducted. We evaluated the proportion of patients achieving serum uric acid (sUA) level ≤6.0 mg/dl at Week 26, and long-term safety and efficacy at Week 52. We also considered efficacy stratified by renal function., Results: Thirty patients (10 at <40 kg and 20 at ≥40 kg) were enrolled. Twenty-four were males, 29 had asymptomatic hyperuricaemia, and 1 had gout. Age was 8 to 18 years. Of these, 63.3% (95% confidence interval 43.9-80.1%) achieved a sUA level of ≤6.0 mg/dl at Week 26. sUA level (mean ± standard deviation) was 5.55 ± 0.87 mg/dl, reduced from 9.01 ± 1.23 mg/dl at baseline. Febuxostat efficacy appeared similar for mild to moderate renal dysfunction and with normal renal function. There were no major safety issues., Conclusions: In paediatric patients with hyperuricaemia including gout, febuxostat showed long-term, well-controlled urate-lowering efficacy with no major safety issues. Findings suggest that no dose adjustment is required for paediatric patients with mild to moderate renal dysfunction., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients., Methods: The Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as a historical, weighted control group. The primary end point for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years., Results: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% [95% confidence interval (CI) 34.7-46.2%] and 28.9% (95% CI 9.9-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years., Conclusions: This study confirmed the 3-year effectiveness and safety and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Congenital melanocytic nevus (CMN) is a benign skin lesion present from birth, which may present with a risk of malignant transformation if extensive. Curettage, a treatment method involving the removal of the superficial layer of the nevus, is often used in the early stages of life. However, recurrence of the nevus and postoperative scarring may present as problems. Additional treatments, such as resection and/or laser treatment, are regularly required after curettage, particularly in the craniofacial region. However, no systematic treatment strategy has been reported. This study investigated additional treatments used after curettage to treat CMN in the craniofacial region and compared the frequency of treatments with respect to specific sites., Methods: CMN cases involving curettage as an initial treatment were retrospectively reviewed at Kyoto University Hospital between May 2019 and April 2022., Results: This study comprised 23 cases. Curettage was performed at a mean of 3.8 (1-10) months of age. No additional treatments were provided for 80% of head CMN. Additional treatments were performed in all cases, including the forehead and cheek. Laser treatment was performed in 86% of eyelid CMN and 75% of nasal CMN. Tissue expansion and flap closure were used in 33% of forehead CMN and 33% of cheek CMN., Conclusions: Additional treatments used for CMN in the craniofacial region varied in accordance with the lesion site., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: To address improvements in quality of life, we analysed the relative contributions of factors to EuroQol 5 Dimensions (EQ-5D) in abatacept-treated rheumatoid arthritis patients in the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study., Methods: Patients who were evaluable for disease activity through to  Week 52 in the ORIGAMI study were divided into those achieving Simplified Disease Activity Index-remission/low disease activity (remission/LDA; n = 178) and patients with moderate disease activity/high disease activity (MDA/HDA; n = 99). We compared the changes in EQ-5D and other outcomes through to Week 52. Focusing on the remission/LDA group, the contribution of each factor to the variance of EQ-5D at baseline and Week 52 was examined using analysis of variance., Results: The remission/LDA group showed greater improvements than the MDA/HDA group in EQ-5D, Japanese Health Assessment Questionnaire, visual analogue scale for pain (Pain VAS), and patient's global assessment (PtGA). In the remission/LDA group, factors significantly contributing to EQ-5D were sex, C-reactive protein, and Pain VAS at baseline, and PtGA and age at Week 52., Conclusions: In rheumatoid arthritis patients who achieved remission/LDA during abatacept treatment, PtGA and age at Week 52 contribute to the variance of EQ-5D, suggesting that the identification of factors associated with PtGA may be important to address improvements in quality of life., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objectives: This article aims to examine the ability of the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk score to predict the occurrence of serious infections in Japanese patients with rheumatoid arthritis (RA), after initiating their first biologic disease-modifying antirheumatic drug (bDMARD)., Methods: We used data from the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2008 to 2020. Patients with RA who were started on their first bDMARDs were included. Those with missing data required to calculate the score were excluded. A receiver operating characteristic curve was used to evaluate the discriminatory ability of the RABBIT score., Results: A total of 1081 patients were enrolled. During the 1-year observational period, 23 (1.7%) patients had serious infections; the most frequent one was bacterial pneumonia (n = 11, 44%). The median RABBIT score in the serious infection group was significantly higher than that in the non-serious infection group [2.3 (1.5-5.4) vs 1.6 (1.2-2.5), P < .001]. The area under the receiver operating characteristic curve for the occurrence of serious infections was 0.67 (95% confidence interval 0.52-0.79), suggesting that the score had low accuracy., Conclusions: Our present study revealed that the RABBIT risk score did not have sufficient discriminatory ability for predicting the development of severe infections in Japanese patients with RA after initiating their first bDMARD., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19)., Methods: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6-August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary., Results: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein., Conclusions: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated., Trial Registration: Japan Registry of Clinical Trials identifier: jRCT2031210350., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

DNA analysis of large herbivore feces samples collected from seagrass beds at two distant sites (Irabu Island in Miyako Islands and Kushi in Okinawa Island) in the Ryukyu Islands proved that some of these feces were from dugongs, which had been treated in recent studies as extinct in this region since the last stranding of a deceased individual in 2019. In addition, local knowledge of sightings of animals thought to be dugongs and confirmed cases of dugong feeding trails since 2010 were compiled to estimate its recent distribution. This is the first scientific report on the presence of this mammal in the Ryukyu Islands within the last four years, and particularly in the Miyako Islands within the last half-century. As the Ryukyu Islands are known to be the northern limit of the dugong's fragmented distribution in East Asia, conservation efforts are therefore needed., (© 2024. The Author(s).)

Objectives: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA)., Methods: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both., Results: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models., Conclusions: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Dietary Reference Intakes for Japanese provide target values for proteins, fats, and carbohydrates. However, they do not provide information on reference values for amino acids (AAs) and fatty acids (FAs), which determine the quality of foods in detail. Therefore, we evaluated AAs and FAs using the Food Exchange Lists-Dietary Guidance for Persons with Diabetes (in Japanese) Utilization, Second Edition Sample Menus and Practice (FELD) as an ideal Japanese diet. Based on FELD, 15 different daily meal patterns were employed with combinations of three levels of carbohydrates %energy (high carbohydrate [HC], 60%; middle carbohydrate [MC], 55%; and low carbohydrate [LC], 50%) and five levels of energy (1,200-2,000 kcal). Using the Japanese Food Composition Table 2020 adjusted for 1,000 kcal, 18 AAs, 49 FAs, and calorie densities (CDs, kcal/g) were calculated and compared among the three groups. Dietary AA was rich in glutamic acid, aspartic acid, and leucine; in order, no significant differences were observed among HC, MC, and LC for 18 AAs. Dietary FA was higher for 18:1 total, 16:0, and 18:2 n-6. Moreover, 16:0, 20:0, and 18:1 total in LC and 22:0 and 18:3 n-3 in MC were significantly higher than those in HC. The HC, MC, and LC CD was low at 0.82, 0.84, and 0.93 kcal/g, respectively. No significant differences in 18 AAs and CD were noted among HC, MC, and LC in FELD; however, significant differences were observed in the FA profiles. This study suggests the importance of evaluating diet using AA and FA units.

To investigate the prevalence of and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis (RA). We analyzed a cross-section of patients with RA participating in the Institute of Rheumatology Rheumatoid Arthritis cohort survey in 2021. Participants completed self-administered questionnaires, including a 5-item sarcopenia screening index (SARC-F). Patients with a SARC-F score of 4 or higher were categorized as having sarcopenia. Among 2416 Japanese patients with RA (2113 women and 303 men; mean age 63.9 years), 341 (14.1%) patients were categorized as having sarcopenia. In a multivariable analysis of patients of all ages, age, body mass index (BMI), disease duration, history of fracture, patient pain on a visual analog scale (VAS), patient or physician global assessments based on VAS, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), biologic disease-modifying antirheumatic drugs (bDMARDs), and corticosteroids were significantly (P < 0.05) associated with sarcopenia. Disease duration, patient global assessments based on VAS, and use of NSAIDs and bDMARDs were significantly associated with sarcopenia among the patients aged < 65 years, whereas age, female sex, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of bDMARDs and corticosteroids were significantly associated with sarcopenia in patients aged ≥ 65 years. In Japanese patients with RA, age, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of NSAIDs, bDMARDs, and corticosteroids were associated with sarcopenia. Among older patients with RA, female sex was additionally associated with sarcopenia. Key Points • To our knowledge, this is the first report showing factors associated with sarcopenia in Japanese patients with rheumatoid arthritis using a large cohort database. • Age, BMI, disease duration, history of fracture, patient pain on a visual analog scale, and use of nonsteroidal anti-inflammatory drugs, biologic disease-modifying antirheumatic drugs, and corticosteroids were associated with sarcopenia in Japanese patients with rheumatoid arthritis. Limited to elderly patients, female sex was also associated with sarcopenia., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Hyaline fibromatosis syndrome (HFS) is a congenital disorder characterized by subcutaneous skin nodules, congenital multiple arthrogryposis, gingival hyperplasia, and chronic pain. The intellectual ability of patients with HFS is generally normal. This syndrome arises from variants of ANTXR2. Thus far, about 100 cases have been reported but few of these were reported from Japan., Methods: This study reports five additional Japanese patients with genetically confirmed HFS, from unrelatd families, and discusses the clinical course and quality of life of these patients., Results: At our last visit the ages of the patients were 3-19 years (the median age was 5 years). All the patients had arthrogryposis, skin nodules, and gingival hyperplasia, and four patients had chronic pain, all of which are distinctive, clinical characteristics of HFS. Four of the patients (80%) had pruritic skin nodules, and three experienced sleep disruptions due to pruritis. The visceral complications are an index of HFS severity. One patient in the present cohort had a mucosal abnormality without any gastrointestinal symptoms., Conclusion: Preventive and routine management of pruritis caused by skin nodules should be shared with the patient's family. Even asymptomatic patients might have endoscopic finding, which would be a soft marker that could predict the development of protein losing enteropathy., (© 2024 Japan Pediatric Society.)

Objectives: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis., Methods: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs., Results: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs., Conclusions: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Regenerative medicine products using allogeneic cells, such as allogeneic cultured epidermis (allo-CE), have become a more critical therapeutic method for the treatment of burns. However, there are no clinically available allo-CE products in Japan. Therefore, establishing a quality-controlled cell bank is mandatory to create regenerative medical products using allogeneic cells. In this study, we selected ten patients from the Department of Plastic Surgery of Kyoto University Hospital to become cell donors. We performed medical interviews and blood sampling for the donor to ensure virus safety. We examined the tissues and isolated cells by performing a nucleic acid test (NAT). To establish a master cell bank, quality evaluation was performed according to the International Conference of Harmonization (ICH) Q5A. Serological tests of the blood samples from the ten donors showed that two of them were ineligible. The cells registered in the cell bank were found to be compatible after virus testing was performed, and a master cell bank was constructed. Hence, we established a keratinocyte and fibroblast bank of clinically usable human cultured cells in Japan for the first time., (© 2022. The Japanese Society for Artificial Organs.)

Objective: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance., Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members., Results: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach., Conclusion: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines., Methods: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members., Results: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopaedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA., Conclusions: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Some of the heaviest snowfalls in urban areas in the world occur in Japan, particularly in regions that face the Japan Sea. Many heavy snowfalls are produced by a Japan Sea polar air mass convergence zone (JPCZ), which is an atmospheric river-like cloud zone that forms when Siberian cold air flows over the warm Japan Sea. Quantifying how the air-sea interaction strengthens the JPCZ is key to snowfall prediction. However, until our observations with hourly meteorological balloon launches from a training vessel in 2022, no simultaneous air-sea observations targeting the JPCZ had been conducted. Our observations showed that wind direction shifted drastically by about 90 degrees from the surface to an altitude of about 3.5 km within a narrow horizontal range of about 15 km, indicating airflow convergence from the surroundings. Maximum temperature difference between surface air (3 °C) and water was 11 °C near the JPCZ centre with 17 m s -1 wind speed. Large amounts of heat, 718 W m -2 , was thus gained from the warm sea. Water vapour was also concentrated by the horizontal convergence, which caused heavy snow, equivalent to 100 cm of snowfall in 7 h. The surrounding sea greatly affects moisture formation within the JPCZ., (© 2022. The Author(s).)

Objectives: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database., Methods: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score)., Results: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5., Conclusions: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers., Competing Interests: ET reports consulting fees from AbbVie Japan GK, Asahi Kasei Corp., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Pfizer Japan Inc. and Takeda Pharmaceutical Co., Ltd. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Corp., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Celltrion Healthcare Japan Co, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd. and UCB Japan Co., Ltd. EI reports consulting fees from Pfizer Japan Inc., Bristol-Myers Squibb Co., Ltd., Nippontect Systems Co., Ltd. and RCR Co., Ltd. AS is an employee of Medilead, Inc., which was commissioned to perform this study analysis by Tokyo Women’s Medical University. JN was employed by ICON plc. for this study. CP is an employee of ICON plc. and reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol-Myers Squibb Co., Ltd. DD is an employee of Bristol-Myers Squibb Co., Ltd. and reports stock or stock options from Bristol-Myers Squibb Co., Ltd. YY is an employee of Bristol-Myers Squibb Co., Ltd. MO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai Pharmaceutical Co., Ltd., Sentan Igaku-Sha Ltd., Asahi Kasei Corp., Bunkodo Co., Ltd., Maruho Co., Ltd., Medical view Co., Ltd. and Kagakuhyoronsya Co., Ltd. KI reports consulting fees from Zimmer Biomet Holdings, Inc.; payment or honoraria for speakers bureaus from AbbVie, Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co. and UCB Japan Co. and for participation on a Data Safety Monitoring Board or Advisory Board from Gilead Sciences, Inc.; and unrestricted grant to Division of Multidisciplinary Management of Rheumatic Diseases from Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd, Nippon Kayaku Co., Ltd. and Teijin Pharma Ltd. HY reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Teijin Pharma Ltd., Eisai Co., Ltd., YLBio, Pfizer Japan Inc., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Bristol-Myers Squibb Co., Ltd., AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Kaken, Nippon Kayaku Co., Ltd., Novartis, Ono, Taisyo-Toyama, Takeda, Torii Pharmaceutical Co., Ltd., UCB Japan Co., Ltd. and MSD. MH reports research grants from Bristol-Myers Squibb K.K.; grants or contracts from AbbVie Japan GK, Kaken Pharmaceutical Co. Ltd., Asahi Kasei Corp., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Taisho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Takeda, Daiichi-Sankyo, Inc., Pfizer Japan Inc. and Eisai Co., Ltd.; consulting fees from AbbVie Japan GK and Bristol-Myers Squibb K.K. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb K.K., Ltd., Pfizer Japan Inc., Chugai Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., UCB Japan Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences Inc. and Janssen Pharmaceutical K.K. MA, KS, ES, NS and RY have no conflicts of interest to report., (Copyright: © 2022 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan., Methods: Abatacept (125 mg) was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension Questionnaire (EQ-5D), treatment retention, and safety. The results were compared with those of conventional synthetic disease-modifying antirheumatic drug (csDMARD) controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry., Results: Overall, 325 patients were enrolled, with a mean age of 66.9 ± 12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3-23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4-59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7-75.5). Adverse events and serious adverse events were reported in 50.0% and 12.1% of patients, respectively., Conclusions: Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

Objectives: The aim of this post-marketing surveillance (PMS) study is to evaluate the real-world safety and efficacy of CT-P13, the first biosimilar of infliximab (IFX)., Methods: Japanese patients with rheumatoid arthritis were prospectively registered from November 2014 and followed up for 1 year., Results: Of 794 patients in the analysis set, 318 patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) showed an immediate decrease in Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and increased remission rate (DAS28-CRP < 2.6). In patients who switched from IFX to CT-P13 for non-medical reasons (n = 374), the low DAS28-CRP due to previous IFX treatment decreased further with continued CT-P13 therapy. As in naïve patients, patients who switched from other bDMARDs, mainly for medical reasons (n = 102), responded similarly to CT-P13. CT-P13 in this PMS and IFX in a previous PMS had similar adverse reaction profiles, although the incidence rate in naïve patients in this current PMS was lower due to earlier initiation of CT-P13 therapy., Conclusions: CT-P13 showed excellent effectiveness as first-line therapy, no clinical difficulties in switching from IFX, and clinical improvement in patients who failed other bDMARDs. CT-P13 could be a cost-effective alternative to IFX in the treatment of rheumatoid arthritis., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

Objectives: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults., Methods: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications., Results: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively., Conclusion: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults., (© 2021 Japan College of Rheumatology.)

This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4 years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25 kg/m 2 (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5 kg/m 2 (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objectives: To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA., Methods: PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system., Results: Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98-1.10) and 0.84 (0.61-1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69-1.26) and 2.15 (0.55-8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76-1.12) and 1.41 (0.32-6.15) in those who continued the reference bDMARDs., Conclusion: Biosimilars and reference bDMARDs were equally useful for the management of RA., (© 2021 Japan College of Rheumatology.)

Background: Our 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., Methods: This 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., Results: Among 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., Conclusions: This 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 Registration: UMIN000036029 ., (© 2021. The Author(s).)

Objective: To evaluate the safety and efficacy of long-term denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) in patients with rheumatoid arthritis (RA)., Methods: This 12-month, randomized, double-blind, placebo-controlled, multicenter, phase III trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese patients with RA treated with placebo (P) for 12 months followed by either denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M) for 24 months; denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp score (mTSS), bone erosion score (BES), and joint space narrowing (JSN) score., Results: Long-term treatment better maintained mTSS and BES suppression in the P/Q3M and Q3M/Q3M vs P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS (standard error) at 36 months were 2.8 (0.4) and 1.7 (0.3) vs 3.0 (0.4) and 2.4 (0.3), respectively, and corresponding changes in BES were 1.3 (0.2) and 0.4 (0.2) vs 1.4 (0.2) and 1.1 (0.2), respectively. No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-terminal telopeptide of type I collagen decreased rapidly at 1 month postdenosumab administration (in both the initial 12-month [Q3M and Q6M groups] and long-term treatment [P/Q3M and P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups., Conclusion: Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on BES progression, higher dosing frequency at an earlier treatment stage may be needed to optimize treatment. Denosumab was generally well tolerated. (ClinicalTrials.gov: NCT01973569)., (Copyright © 2021 by the Journal of Rheumatology.)

Objectives: In patients with gout, treating to target serum uric acid levels (sUA) of ≤6.0 mg/dL is universally recommended to prevent gout flare. However, there is no consensus on asymptomatic hyperuricaemia. Using Japanese health insurance claims data, we explored potential benefits of sUA control for preventing gout flare in subjects with asymptomatic hyperuricaemia., Methods: This retrospective cohort study analysed the JMDC Claims Database from April 2012 through June 2019. Subjects with sUA ≥8.0 mg/dL were identified, and disease status (prescriptions for urate-lowering therapy (ULT), occurrence of gout flare, sUA) was investigated for 1 year. Time to first onset and incidence rate of gout flare were determined by disease status subgroups for 2 years or more. The relationship between gout flare and sUA control was assessed using multivariable analysis., Results: The analysis population was 19 261 subjects who met eligibility criteria. We found fewer occurrences of gout flare, for both gout and asymptomatic hyperuricaemia, in patients who achieved sUA ≤6.0 mg/dL with ULT than in patients whose sUA remained >6.0 mg/dL or who were not receiving ULT. In particular, analysis by a Cox proportional-hazard model for time to first gout flare indicated that the HR was lowest, at 0.45 (95% CI 0.27 to 0.76), in subjects with asymptomatic hyperuricaemia on ULT (5.0

In this study, we assess the association between the occurrence of new fractures and vitamin D deficiency in Japanese patients with rheumatoid arthritis using our large IORRA cohort. The results suggest that vitamin D deficiency is a significant risk factor for new fractures in Japanese female patients over the age of 50 years with rheumatoid arthritis., Purpose: Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures., Methods: Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50 years (mean age, 65.9 years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20 ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture., Results: New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02‒2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14‒2.69]; p = 0.0109)., Conclusion: Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50 years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Purpose: This study assessed factors associated with achieving target serum uric acid (sUA) level and occurrence of gouty arthritis in Japanese clinical practice., Methods: Japanese health insurance claims and medical check-up data from October 2015 to March 2017 were analyzed to assess factors associated with target sUA achievement in gout and asymptomatic hyperuricemia and gouty arthritis in gout. Target sUA was further assessed by subgroup analysis of urate-lowering therapy (ULT) prescriptions and outcomes, stratified by renal function., Results: Patients achieving target sUA tended toward older, female, higher ULT dose, higher adherence, more comorbidities, and/or antidiabetic drugs prescribed. Renal dysfunction and/or diuretic prescriptions were associated with reduced achievement of target sUA. Severe renal dysfunction was particularly influential (odds ratio [OR] = 0.22 [95% confidence interval (CI): 0.10-0.48] for <15, 0.15 [0.10-0.23] for ≥15 to <30, compared with eGFR ≥90 mL/min/1.73 m 2 ). Across all renal function categories, mean prescribed ULT dose was low (febuxostat 17.0-21.0 mg/day, allopurinol 123.1-139.6 mg/day), and target sUA achievement was reduced among renal dysfunction patients. Gouty arthritis was more likely in patients with a prior history of such occurrences, and less likely for higher ULT adherence, sUA monitored regularly at medical facilities, and/or more comorbidities., Conclusion: In a real-world setting, severe renal dysfunction is the most important risk factor for failure to achieve the target sUA, suggesting suboptimal disease management in patients with gout or hyperuricemia complicated by this condition. Findings associated with gouty arthritis suggest that these occurrences could be successfully managed by regular monitoring of sUA and closer adherence to ULT., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: To assess gout and asymptomatic hyperuricemia in Japan and review treatment conditions., Methods: This retrospective cross-sectional study analyzed the prevalence of hyperuricemia and gout, and characteristics and treatment of patients with those conditions, using Japanese health insurance claims and medical check-up data collected from April 2016 through March 2017., Results: Among 2,531,383 persons registered in the database, 1.1% (men 1.9%, women <0.1%) were diagnosed with gout and 2.6% (4.1%, 0.4%) with asymptomatic hyperuricemia. Medical check-ups showed 13.4% (19.6%, 1.0%) of patients with hyperuricemia (serum uric acid [sUA] > 7.0 mg/dL). Urate-lowering therapy (ULT) was prescribed for 80.7% of patients identified with gout and 72.4% identified with asymptomatic hyperuricemia. ULT adherence was satisfactory, but most patients were treated with low-dose ULT. Less than half of patients receiving ULT achieved the sUA target (≤6.0 mg/dL). In gout patients, the incidence of gout flare was 47.8% (0.74 flares/person-year)., Conclusions: Although hyperuricemia prevalence is similar in Japan and worldwide, gout is comparatively rare in Japan. Gout and asymptomatic hyperuricemia are often treated with low-dose ULT, and many patients fail to reach target sUA, suggesting that gout management is suboptimal in Japan. Patients would benefit from stricter focus on a treat-to-target approach for gout management.

Objectives: To elucidate the epidemiological characteristics of patients with rheumatoid arthritis (RA) in Japan using data from the Comprehensive Survey of Living Conditions, a nationwide questionnaire survey conducted in 2016. Methods: In total, 222,365 men and 245,251 women aged ≥16 years were included in the study. RA patients were defined as those who reported 'currently receiving treatment for RA at hospitals, clinics, or a facility for Japanese traditional massage, acupuncture, moxibustion, or judo-orthopedics.' The number of RA patients was estimated from the age-specific prevalence and total Japanese population in 2016. Further, the prevalence of individuals experiencing difficulties in activities of daily living due to health problems and those with mental distress as evaluated by K6 Scale was examined. Results: The estimated number and prevalence of RA in Japan with 95% confidence interval was 822 (768-880) thousand and 0.75% (0.70-0.80%). The population peaked in the late 60s, and the prevalence continued increasing until the early 80s, regardless of sex. Compared with non-RA participants, RA patients were more likely to experience difficulties in activities and to be distressed. Conclusion: High prevalence of RA in older age and mental and physical burden among RA patients were confirmed.

Background: Although 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., Methods: This 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., Results: Total 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., Conclusions: Even 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 Registration: UMIN000036029 .

Objectives: The Childhood Health Assessment Questionnaire (CHAQ) is one of the most widely used self- report questionnaires to measure functional status in Juvenile idiopathic arthritis (JIA). The Japanese version of the CHAQ (JCHAQ) has been revised to meet requirements of clinical international trials which need the same number of questions in each functional area of the CHAQ. Methods: The original JCHAQ consisted of 36 items, measuring eight functional areas. This was changed to 30 items of questionnaire so that each functional area has same number of questions as the original US English version. The revised version was professionally translated from English to Japanese, reviewed, and validated with Japanese JIA patients. Results: A total of 42 JIA patients were enrolled in the validation: seven systemic, 30 polyarticular/oligoarticular and five enthesis related. Most patients were well controlled and the median disability index (DI) scores was 0.0 [0-0.03]; however, significant correlation was seen with visual analog scale (VAS) of pain, VAS overall well-being, physician VAS, DAS (Disease Activity Score) 28-ESR, and JADAS (Juvenile Arthritis Disease Activity Score)-27. In comparison of two groups of disease activity, remission or inactive/low disease activity vs. moderate/high disease activity, both DAS28-ESR and JADAS-27 showed significant correlation with DI. Conclusion: The updated JCHAQ was a reliable and valid tool for the functional assessment of children with JIA. It is more suitable for international and transitional comparison.

Panton-Valentine leukocidin (PVL)-positive USA300 clone is a highly pathogenic and global epidemic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone. Athletes are particularly vulnerable to CA-MRSA infection because of the frequency of skin trauma, close-contact situations, and sharing of equipment that is customary in the athletic setting. We experienced a case of Japanese collegiate football player with septic pulmonary emboli secondary to infectious iliofemoral deep venous thrombosis caused by the USA300 clone. Here, we screened the nasal carriage of USA300 clone colonization among asymptomatic teammate of the patient to elucidate the infection route. Among 69 nasal samples, CA-MRSA strains were found in 5.8% (four samples). Molecular epidemiological analyses showed that three of the CA-MRSA strains were USA300 clone. Furthermore, pulsed-field gel electrophoresis revealed that all nasal USA300 clones showed 100% identity with the USA300 clone isolated from their teammate with critical infection. Our findings indicate that nasal colonization of the PVL-positive CA-MRSA, especially USA300 clone, pose a threat among contact sport athletes in Japan likewise other countries. An immediate infection control strategy for contact sport athletes is necessary to prevent outbreaks of PVL-positive CA-MRSA infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: This study aimed to evaluate the prevalence of, and the factors associated with, periodontal disease in Japanese patients with rheumatoid arthritis (RA). Methods: Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed three self-administered questionnaires including questions about recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and any history of periodontitis. Logistic regression analyses were used to evaluate associations with clinical variables for each questionnaire. Results: Among 5600 Japanese patients with RA, 31.0%, 18.3%, and 20.4% of patients self-reported recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and a history of periodontitis, respectively. In multivariate models, younger age, fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), and prednisolone dosage were significantly ( p  < .05) associated with recent gingival bleeding during toothbrushing. Older age, female gender, and ever-smoker status were significantly correlated with a recent diagnosis of periodontitis. Conclusion: Many Japanese patients with RA experience gingival bleeding during toothbrushing and are diagnosed with periodontitis. Age, female gender, ever-smoker status, fracture history, JHAQ-DI, and prednisolone dosage appeared to be associated with periodontal disease in Japanese patients with RA.

Aim: The Certolizumab-Optimal Prevention of joint damage for Early Rheumatoid Arthritis (C-OPERA) study demonstrated that in methotrexate (MTX)-naïve early RA patients with poor prognostic factors, 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year optimized MTX therapy brings radiographic and clinical benefits through 2 years even after stopping CZP. This exploratory analysis aimed to identify factors at baseline and at CZP discontinuation associated with successful CZP discontinuation., Methods: MTX-naïve early RA patients with poor prognostic factors entered C-OPERA (NCT01451203), a multicenter, randomized controlled trial. Patients were randomized to CZP + MTX (n = 159) or PBO + MTX (n = 157); those who completed the 1-year, double-blind period received MTX alone in Year 2 (CZP + MTX→MTX, n = 108; PBO + MTX→MTX, n = 71). Association between factors at baseline or at discontinuation of CZP and clinical/radiographic outcomes were evaluated by multiple logistic regression analysis. Predictive value cut-offs were calculated using receiver operating characteristic analysis., Results: Sex (male) and low baseline Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) were associated with simple disease activity index (SDAI) remission (≤3.3), whereas high baseline DAS28-ESR and modified total Sharp score (mTSS) were associated with clinically relevant radiographic progression (yearly progression mTSS > 3) at Week 104 (across both treatment arms). Low DAS28-ESR (<2.1) and rheumatoid factor (RF; <74 IU/mL) at discontinuation of CZP were associated with SDAI remission at Week 104. At Week 104, SDAI remission was achieved by 75.0% (42/56) of patients with low DAS28-ESR and RF at discontinuation, compared to 15.4% (2/13) of patients with high DAS28-ESR and RF., Conclusion: Patients with low RF and low disease activity after treatment with CZP + MTX may be able to discontinue CZP without risk of loss of response., (© 2020 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Real-world evidence, based on real-world data from routine clinical treatment, is becoming increasingly important for providing high-quality medical care. Large-scale cohort studies can provide useful access to some of this real-world evidence, as shown by the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) cohort in Japan. This large cohort study of patients with rheumatoid arthritis (RA) has been surveying enrolled participants since its inception in 2000. In the last 19 years, it has served as a database for a wide range of research in areas including transitions in medical care at the clinical level, changes in therapeutic drugs, approaches to comorbidities, developments in pharmacoeconomics, and the effects of genomic information on treatment options. This research has resulted in the publication of 133 articles in English to date. IORRA monitors changes in the management of RA, and has quantified over time the daily experience of clinicians who provide routine medical care. Such observational databases, which reflect the reality of daily clinical practice, will become increasingly important and may provide a model for similar research in other disease areas.

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., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Effects of using mobile devices on childhood obesity have not been well studied. We aimed to ascertain whether cell phone use and screen viewing are associated with excess body weight in a cross-sectional study of Japanese school children. Methods: Subjects were 3141 students, ages 6 to 7 years, who participated in the Hekinan Children's Study conducted during 2011-2015. Participants were asked to submit a parent-administered questionnaire on child and parent demographics, health status, and lifestyles, including cell phone use and screen time. Heights and weights were measured at the schools. Being overweight was defined according to the cutoff point for children specified by the Extended International Obesity Task Force. Among 2596 analytic children, the odds ratios (ORs) for being overweight were estimated according to cell phone use, time spent watching television, and time spent on games and computers using the logistic regression models. Analyses were conducted after adjustments for potential confounders, including dietary intake, physical activities, sleep duration, and quality of sleep. Results: After multivariate adjustments, cell phone users were found to have an OR of 1.74 for being overweight compared with nonusers. Cell phone use of longer duration was associated with higher risk of being overweight (trend p  = 0.018). Time spent watching television was positively associated with the risk of being overweight (trend p  = 0.003). Conclusions: Just as earlier studies have shown for television viewing, cell phone use might be a risk factor related to being overweight among children.

Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis patients. Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2. Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p  = .021) and infections (4.8% vs. 7.2%, p  = .002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline. Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.

Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.

Background: The early life environment is now recognized as a key factor contributing to susceptibility to certain diseases in later life., Methods: We initiated a cohort study among school children in 2011 to primarily investigate the associations between lifestyle and environmental factors and some surrogate markers of chronic diseases, such as cardiometabolic risk factors (ie, obesity, high blood pressure, high blood glucose, insulin, or lipids) and cancer risk factors (ie, height and age at menarche). A baseline questionnaire asked for information, including demographic variables, medical history and use of medication, dietary habits, physical activity, sleep habits, and behavioral and emotional problems of children. Follow-up surveys are planned for the fourth grade of elementary school and the first grade of junior high school. At these follow-up surveys, fasting blood samples will be obtained to measure cardiometabolic markers. We also checked the validity of a food frequency questionnaire, which was originally created for 6-year-olds but was modified for use in older children., Results: A total of 3,141 first-year students at elementary schools in Hekinan City, Aichi Prefecture, participated in the study. The response rate was 87.4%. The means of age and body mass index were 6.99 (standard deviation, 0.28) years and 15.3 (standard deviation, 1.7) kg/m 2 , respectively, in the 3,067 Japanese children (1,639 boys and 1,428 girls)., Conclusions: This cohort will reveal determinants of cardiometabolic risk factors and cancer risk factors during childhood.

Objectives: This real-world study assessed the effectiveness and safety outcomes of initiating adalimumab and methotrexate (≥12 mg/week) with adjustable dosing in Japanese patients with early rheumatoid arthritis (RA). Methods: This single-arm, prospective postmarketing observational study (conducted from September 2012 to March 2017 at 119 sites) enrolled biologic-naïve patients with early RA (≤2 years duration) and a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) >3.2 who were treated with methotrexate for ≥3 months and had initiated treatment with adalimumab and methotrexate (≥12 mg/week). This report presents 52-week data. The primary outcome was the proportion of patients who achieved DAS28-CRP scores <2.6 at week 52. Results: Overall, 293 of 346 enrolled patients were included in the effectiveness population: women, 73%; mean (standard deviation) age, 54.3 (13.9) years; DAS28-CRP score, 4.51 (0.90); and modified total Sharp score (mTSS), 7.69 (9.98). At week 52, 77% of patients achieved clinical remission (DAS28-CRP <2.6), 92.3% achieved low disease activity (DAS28-CRP ≤3.2), and 86% of evaluable patients experienced structural remission (ΔmTSS ≤0.5). Conclusion: Adalimumab plus methotrexate (≥12 mg/week) with adjustable dosing was well tolerated, and could be a beneficial treatment option for Japanese patients with early RA.

Objectives: To evaluate the efficacy of denosumab for progressive bone erosion in risk factor subgroups of Japanese RA patients., Methods: This study included 340 RA patients on MTX from the dose-response study of Denosumab in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE study-a 12-month, multicentre, randomized, double-blind, placebo-controlled, phase II study). The patients were randomized to receive placebo or denosumab 60 mg every 6 months, 3 months or 2 months. Subgroup analyses involved baseline RF, ACPA, swollen joint count, CRP level, RA duration, ESR and glucocorticoid use., Results: Patients with risk factor positivity generally showed consistent results for the primary endpoint of the change in the modified Sharp erosion score at 12 months from baseline. In the placebo, every 6 months, every 3 months and every 2 months groups, the mean changes in the erosion score, according to the RF status (RF-positive vs -negative subgroups), were 1.18 vs 0.59, 0.25 (P = 0.0601 vs placebo) vs 0.31 (P = 0.0827), 0.21 (P = 0.0422) vs -0.02 (P = 0.0631) and 0.15 (P = 0.0010) vs -0.05 (P = 0.0332), respectively, while the mean changes in the erosion score, according to the ACPA status (ACPA-positive vs -negative subgroups), were 1.30 vs 0.07, 0.26 (P = 0.0142) vs 0.33 (P = 0.2748), 0.16 (P = 0.0058) vs 0.08 (P = 0.7166) and 0.09 (P < 0.0001) vs 0.08 (P = 0.8939), respectively., Conclusion: Denosumab is a potentially useful treatment option for RA patients who are positive for RF, ACPA and other possible risk factors., Trial Registration: JAPIC Clinical Trials Information, http://www.clinicaltrials.jp/user/cteSearch&#95;e.jsp, JapicCTI-101263., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy., Methods: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed. Results 116/878 patients received sirukumab 50 mg/4 weeks (q4w, n = 35), 100 mg/2 weeks (q2w, n = 44) or placebo (n = 37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50 mg q4w:20 [57.1%]; p < .001, 100 mg q2w:24 [54.5%]; p = .001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50 mg q4w:29 [82.9%]; 100 mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs., Conclusion: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.

The use of environmental DNA (eDNA) methods for community analysis has recently been developed. High-throughput parallel DNA sequencing (HTS), called eDNA metabarcoding, has been increasingly used in eDNA studies to examine multiple species. However, eDNA metabarcoding methodology requires validation based on traditional methods in all natural ecosystems before a reliable method can be established. To date, relatively few studies have performed eDNA metabarcoding of fishes in aquatic environments where fish communities were intensively surveyed using multiple traditional methods. Here, we have compared fish communities' data from eDNA metabarcoding with seven conventional multiple capture methods in 31 backwater lakes in Hokkaido, Japan. We found that capture and field surveys of fishes were often interrupted by macrophytes and muddy sediments in the 31 lakes. We sampled 1 L of the surface water and analyzed eDNA using HTS. We also surveyed the fish communities using seven different capture methods, including various types of nets and electrofishing. At some sites, we could not detect any eDNA, presumably because of the polymerase chain reaction (PCR) inhibition. We also detected the marine fish species as sewage-derived eDNA. Comparisons of eDNA metabarcoding and capture methods showed that the detected fish communities were similar between the two methods, with an overlap of 70%. Thus, our study suggests that to detect fish communities in backwater lakes, the performance of eDNA metabarcoding with the use of 1 L surface water sampling is similar to that of capturing methods. Therefore, eDNA metabarcoding can be used for fish community analysis but environmental factors that can cause PCR inhibition, should be considered in eDNA applications., Competing Interests: The authors have declared that no competing interests exist.

Background: Foot and ankle joint disorders are serious issues for patients with rheumatoid arthritis (RA). We compared the differences between patients with RA whose first symptom involved a foot or ankle joint (FOOT group) versus other joints (non-FOOT group) within the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort in our institute., Patients and Methods: In the IORRA survey conducted in April 2016, patients were invited to complete six questionnaires about their first symptom at RA onset, current foot or ankle symptoms, daily living activities, and mental health. Disease activity, clinical laboratory variables, functional disability, quality of life, use and ratio of anti-inflammatory and antirheumatic drugs, daily living activities and mental health were compared between the two groups., Results: Among 5,637 Japanese patients with RA who participated in the IORRA survey on April 2016, 5,479 (97.2%) responded to the questionnaire regarding their debut joint. Of these patients, 2,402 (43.8%) reported that their first symptom of RA involved a foot or ankle joint. The FOOT group (n = 2,164) had higher disease activity, higher disabilities, lower quality of life, lower activities of daily living, and poorer mental health and used anti-inflammatory drugs at a higher rate and at higher doses compared with the non-FOOT group (n = 2,164). On the other hand, the use of medications to suppress the disease activity of RA was similar between the groups., Conclusion: Clinicians should pay more attention to foot and ankle joints in daily practice so as not to underestimate the disease activity of RA., Competing Interests: KY has received speakers bureau from Eisai, AbbVie, Astellas, Mochida, Hisamitsu, Bristol-Meyers, Takeda and Ayumi. KI has received speakers bureau from Astellas, AbbVie, Bristol-Meyers, Chugai, Janssen Pharmaceutical, Lilly, Takeda, Tanabe-Mitsubishi and UCB. TM has received speakers bureau from Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Janssen, and Mitsubishi Tanabe. ET has received lecture fees or consulting fees from Abbvie, Ayumi Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, and UCB. AT has received Research Grant from Chugai. HY has received Research Grant from MSD, Astellas, AbbVie, BMS, Kaken, UCB, Ono, Ayumi, Eisai, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin, Torii, Nipponshinyaku, and Pfizer, Lecture/Consultant fee from Pfizer, YL biologics, Takeda, Teijin, BMS, Nipponkayaku, Chugai, Tanabe-Mitsubishi, Daiichi-Sankyo and Astellas. IORRA is supported by various grants from Tokyo Women's Medical University and a large number of pharmaceutical companies; AbbVie, Asahi Kasei Pharma, Astellas Pharma, Ayumi, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Japan Tobacco, Kaken Pharmaceutical, Kissei Pharmaceutical, Kyowa Pharma Chemical, Maruho, Mochida Pharmaceutical, MSD, Nippon Chemiphar, Nippon Kayaku, Nippon Shinyaku, Pfizer, Ono Pharmaceutical, Otsuka Pharmaceutical, Sekisui medical, Shionogi, Taisho Toyama Pharmaceutical, Takeda, Tanabe-Mitsubishi Pharma, Teijin Pharma, Torii Pharmaceutical and UCB. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Information about species distribution is crucial to ecological studies. Environmental DNA (eDNA) analysis has recently been used to estimate the distribution of aquatic organisms. Several analytical methods including metabarcoding and species-specific PCR are being used for eDNA analysis. However, when only a few species are targeted, metabarcoding is not cost-effective because of the wasted consumption of read due to amplification of non-target species DNA. On the other hand, species-specific PCR requires tests to be repeated multiple times resulting in consuming more DNA templates, and experimental consumables. Here we propose a methodological framework for simultaneously detecting a few species using real-time multiplex PCR. We developed the species-specific primer-probe sets for two species of Japanese medaka (Oryzias latipes and o. sakaizumii), and we used them in the real-time multiplex PCR. In aquarium experiment, even when the species abundances were biased, both species were simultaneously detected in all samples. In a field survey, eDNA analysis and capture survey produced consistent results in all sampling sites, including sites with low fish densities. eDNA analysis using real-time multiplex PCR can be easily applied to other aquatic organisms, enabling a more cost-effective distribution survey of multiple target organisms.