Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: results from the IORRA cohort.

OBJECTIVES: We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. METHODS: Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. RESULTS: We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). CONCLUSION: Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update an evidence base informing the 2024 JCR clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) in older adults. METHODS: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs (bDMARDs), CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: Observational studies confirmed a pivotal role of MTX in the treatment of older RA patients. The meta-analysis showed that tumor necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that bDMARDs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. CONCLUSION: This systematic review provides the necessary evidence for developing 2024 JCR CPGs for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired.

Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past 17 years: Analyses from the IORRA cohort.

OBJECTIVES: The aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years. METHODS: Japanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001-06) and B (2007-12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated. RESULTS: Groups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59-1.08) and 0.78 (0.57-1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68-1.19) for Group A and 0.92 (0.68-1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively. CONCLUSIONS: The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

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 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 an historical, weighted control group. The primary endpoint 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.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

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.

Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.

Development of a scoring model for the Sharp/van der Heijde score using convolutional neural networks and its clinical application.

OBJECTIVES: To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. MATERIAL AND METHODS: A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features. RESULTS: In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of ΔSHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model. CONCLUSION: A high-performance scoring model for SHS that is applicable to clinical research was constructed.

Association of disease activity using SDAI and DAS28, but not JADAS-27, with subsequent changes in physical function in adult patients with juvenile idiopathic arthritis.

OBJECTIVES: To investigate an optimal composite score for disease activity in adult JIA from the viewpoint of the subsequent changes in physical function. METHODS: Patients with JIA under the following conditions were enrolled: 1) disease onset < 18 years; 2) registered in the database by Tokyo Women's Medical University for the first time between 2000 and 2020; and 3) ≥18 years old at the time of registration. Patients were stratified according to mean disease activity scores in SDAI, DAS28, and JADAS-27 during the first year from baseline. Trends of estimated mean change in Japanese-HAQ score (ΔJ-HAQ) from baseline to 2 years later was examined across the stratified groups of each index. RESULTS: We included 294 eligible individuals (median age at onset, 14.0 years; RF positive in 64.7%). A significant increasing trend of the estimated mean ΔJ-HAQ at 2 years after baseline was observed along with an increase in the mean disease activity during the first year measured using DAS28 (p = 0.01) and SDAI (p = 0.018), but not using JADAS-27. CONCLUSIONS: Disease activity measured using SDAI and DAS28, but not using JADAS27, was significantly associated with subsequent changes in physical function in adult patients with JIA.

Surgical intervention for patients with rheumatoid arthritis is declining except for foot and ankle surgery: A single-centre, 20-year observational cohort study.

OBJECTIVES: A global downward trend in the number of rheumatoid arthritis (RA)-related surgeries has been reported. The purpose of our study was to investigate the latest trends in RA-related surgeries in a single-centre Japanese RA cohort. METHODS: This study was a retrospective analysis of RA-related surgeries between 2001 and 2020 in the Institute of Rheumatology Rheumatoid Arthritis cohort. An average of 4944 patients per semi-annual survey was included in the study. The primary goal was to analyse the half-year period prevalence proportion (HPP) of RA-related surgeries in a 20-year period, and the secondary goal was to analyse the HPP of surgeries by site or by categories of disease activity. RESULTS: There has been a downward trend in the HPP of RA-related surgeries in the 20-year study period. The total HPP of RA-related surgeries decreased by 50.3% during the 20-year study period. There was a significant decrease in knee, hip, shoulder/elbow, and hand procedures. Only foot/ankle joint surgeries significantly increased in volume during this period (p = .001). The HPP of RA-related surgeries remained unchanged in patients with remission or low disease activity. CONCLUSIONS: The number of RA-related surgeries decreased over a 20-year period, but foot/ankle joint surgeries increased in the site-specific evaluation.

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.

Contribution of the factors to EuroQol 5 Dimensions in rheumatoid arthritis patients achieving low disease activity/remission with abatacept treatment: post-hoc subgroup analyses of the Japanese real-world observational "ORIGAMI" study.

OBJECTIVES: To address improvements in quality of life (QOL), we analysed the relative contributions of factors to EuroQol 5 Dimensions (EQ-5D) in abatacept-treated rheumatoid arthritis (RA) patients in the 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/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 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 RA patients who achieved remission/LDA during abatacept treatment, PtGA and age at Week 52 contribute to the variance of EQ-5D, suggesting that identification of factors associated with PtGA may be important to address improvements of QOL.

Evaluation of RABBIT risk score in Japanese patients with rheumatoid arthritis starting first bDMARDs: a validation study using the IORRA cohort data.

OBJECTIVE: 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 (IORRA) 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 (ROC) curve was used to evaluate the discriminatory ability of the RABBIT score. RESULTS: A total of 1,081 patients were enrolled. During the one-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<0.001). The area under the ROC curve for the occurrence of serious infections was 0.67 (95% confidence interval 0.52-0.79), suggesting that the score had low accuracy. CONCLUSION: 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 rheumatoid arthritis after initiating their first bDMARD.

Trends in risks of malignancies in Japanese patients with rheumatoid arthritis: Analyses from a 14-year observation of the IORRA cohort.

OBJECTIVES: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. RESULTS: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. CONCLUSIONS: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.

Non-drug and surgical treatment algorithm and recommendations for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

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.

Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

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.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

A SARS-CoV-2 Delta variant containing mutation in the probe binding region used for RT-qPCR test in Japan exhibited atypical PCR amplification and might induce false negative result.

INTRODUCTION: A recent pandemic of SARS-CoV-2 infection has caused severe health problems and substantially restricted social and economic activities. RT-qPCR plays a vital role in the diagnosis of SARS-CoV-2 infection. The N protein-coding region is widely analyzed in RT-qPCR to diagnose SARS-CoV-2 infection in Japan. We recently encountered two cases of SARS-CoV-2-positive specimens showing atypical amplification curves in the RT-qPCR. METHODS: We performed whole-genome sequencing of 63 samples (2 showing aberrant RT-qPCR curve and 61 samples infected with SARS-CoV-2 simultaneously in the same area) followed by Phylogenetic tree analysis. RESULTS: We found that the viruses showing abnormal RT-qPCR curves were Delta-type variants of SARS-CoV-2 with a single nucleotide mutation in the probe-binding site. There were no other cases with the same mutation, indicating that the variant had not spread in the area. After searching the database, hundreds of variants were reported globally, and one in Japan contained the same mutation. Phylogenetic analysis showed that the variant was very close to other Delta variants endemic in Japan but quite far from the variants containing the same mutation reported from outside Japan, suggesting sporadic generation of mutant in some domestic areas. CONCLUSIONS: These findings propose two key points: i) mutations in the region used for SARS-CoV-2 RT-qPCR can cause abnormal amplification curves, and ii) various mutations can be generated sporadically and unpredictably; therefore, efficient and robust screening systems are needed to promptly monitor the emergence of de novo variants.

Impact of concomitant chronic kidney disease on hospitalised infections and remission in patients with rheumatoid arthritis: results from the IORRA cohort.

OBJECTIVES: To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). METHODS: We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to < 60; moderate CKD, eGFR ≥30 to < 45; and severe CKD, eGFR <30. We assessed the association between concomitant CKD and the occurrence of unfavourable clinical events or achieving remission during a 5-year observational period. RESULTS: Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07-2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12-3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68-0.99, p = .04). CONCLUSIONS: Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.