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In the past few decades, physicians have been able to effectively manage patients with rheumatoid arthritis (RA) thanks to advances in treatment strategies including molecular-targeting drugs [...].In the past few decades, physicians have been able to effectively manage patients with rheumatoid arthritis (RA) thanks to advances in treatment strategies including molecular-targeting drugs [...].

Introduction Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. We investigated the risk factors for vertebral fractures and severe vertebral fractures in patients with RA, including comorbidities and urinary pentosidine levels. Materials and methods This study included 637 patients with available clinical data on urinary pentosidine levels, vertebral fractures, and comorbidities. Vertebral fractures were evaluated using plain X-ray imaging. Comorbidities considered relevant to osteoporosis were type 2 diabetes mellitus, chronic kidney disease, and lung diseases. Results The prevalence of vertebral fractures in this cohort was 30.1%. Patients with vertebral fracture Patients with vertebral fractures were significantly more likely to be older [odds ratio (OR) 1.075; 95% confidence interval (CI) 1.049–1.1.03], had higher prevalence of comorbidities (OR 1.770; 95% CI 1.138–2.753), higher urinary pentosidine levels (OR 1.028; 95% CI 1.013–1.044), higher history of non-vertebral fractures (OR 2.084; 95% CI 1.222–3.557), and lower total hip T-score (OR 0.526; 95% CI 0.329–0.841) than patients without vertebral fractures. Among patients with vertebral fractures, 54.2% had severe vertebral fractures. Patients with severe vertebral fractures were more likely to have lower lumbar spine T-scores (OR 0.768; 95% CI 0.622–0.949) than patients with non-severe vertebral fractures. Conclusions This study identified factors associated with vertebral fractures and severe vertebral fractures in patients with RA. Notably, vertebral fractures were associated with comorbidities and urinary pentosidine levels. In patients with RA and vertebral fractures, low BMD in the lumbar spine was a significant factor associated with severe vertebral fractures.

Purpose The purpose of this study was to evaluate perioperative and short-term clinical and radiographical results of a modern PS mobile-bearing cementless TKA system. Methods A retrospective review of a consecutive series of TKAs was performed by a single surgeon using a cementless or cemented TKA of the same design (Attune, DePuy Synthes, Massachusetts, USA). The 2011 Knee Society Score, Forgotten Joint Score-12, Hip-Knee-Ankle angle, and the presence of radiolucent lines (RLLs) were reviewed 1-year postoperatively with 1:1 matching performed for age, gender, body mass index, and preoperative UCLA score. Fisher’s exact test or independent Student’s t -test were used for statistical analyses. Results Forty-five cementless and 45 cemented TKAs were reviewed after 1:1 matching. The mean operative time was 8.8 min shorter ( P  < .01), and the mean amount of drainage was 40.0 ml greater ( P  = .04) in the cementless cohort. At 1-year postoperatively, there were no significant differences in both cohorts in 2011 Knee Scores and Forgotten Joint Scores-12, with no patients requiring revision surgery (NS). The incidence of RLLs was significantly higher in cementless TKAs (51%) than that in cemented TKAs (22%, P  < .01). However, the mean width of RLLs in the cementless TKAs (0.2 mm) was significantly smaller ( P  < .01) than that in the cemented TKAs (0.8 mm) at 1-year postoperatively with no progression. Conclusion A recently introduced cementless PS mobile-bearing TKA design demonstrated comparable postoperative and radiographical results to its cemented predecessor at 1-year follow-up. Level of Evidence Retrospective cohort study, Level III.

ObjectiveExtracting immunological and clinical heterogeneity across autoimmune rheumatic diseases (AIRDs) is essential towards personalised medicine.MethodsWe conducted large-scale and cohort-wide immunophenotyping of 46 peripheral immune cells using Human Immunology Protocol of comprehensive 8-colour flow cytometric analysis. Dataset consisted of >1000 Japanese patients of 11 AIRDs with deep clinical information registered at the FLOW study, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In-depth clinical and immunological characterisation was conducted for the identified RA patient clusters, including associations of inborn human genetics represented by Polygenic Risk Score (PRS).ResultsMultimodal clustering of immunophenotypes deciphered underlying disease-cell type network in immune cell, disease and patient cluster resolutions. This provided immune cell type specificity shared or distinct across AIRDs, such as close immunological network between mixed connective tissue disease and SLE. Individual patient-level clustering dissected patients with AIRD into several clusters with different immunological features. Of these, RA-like or SLE-like clusters were exclusively dominant, showing immunological differentiation between RA and SLE across AIRDs. In-depth clinical analysis of RA revealed that such patient clusters differentially defined clinical heterogeneity in disease activity and treatment responses, such as treatment resistance in patients with RA with SLE-like immunophenotypes. PRS based on RA case–control and within-case stratified genome-wide association studies were associated with clinical and immunological characteristics. This pointed immune cell type implicated in disease biology such as dendritic cells for RA-interstitial lung disease.ConclusionCohort-wide and cross-disease immunophenotyping elucidate clinically heterogeneous patient subtypes existing within single disease in immune cell type-specific manner.

Yuta Kochi and colleagues perform expression quantitative trait loci (eQTL) analysis on five subsets of immune cells individually sorted from blood from 105 individuals. They develop an integrated analysis pipeline of expression and epigenomic data along with gene association to identify cell-specific candidate causal genes and apply this to rheumatoid arthritis. Recent evidence suggests that a substantial portion of complex disease risk alleles modify gene expression in a cell-specific manner 1 , 2 , 3 , 4 . To identify candidate causal genes and biological pathways of immune-related complex diseases, we conducted expression quantitative trait loci (eQTL) analysis on five subsets of immune cells (CD4 + T cells, CD8 + T cells, B cells, natural killer (NK) cells and monocytes) and unfractionated peripheral blood from 105 healthy Japanese volunteers. We developed a three-step analytical pipeline comprising (i) prediction of individual gene expression using our eQTL database and public epigenomic data, (ii) gene-level association analysis and (iii) prediction of cell-specific pathway activity by integrating the direction of eQTL effects. By applying this pipeline to rheumatoid arthritis data sets, we identified candidate causal genes and a cytokine pathway (upregulation of tumor necrosis factor (TNF) in CD4 + T cells). Our approach is an efficient way to characterize the polygenic contributions and potential biological mechanisms of complex diseases.

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.

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. 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. 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. Clinicians should pay more attention to foot and ankle joints in daily practice so as not to underestimate the disease activity of RA.

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. 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). 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. ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Graphical Abstract

BackgroundThe aim of this study was to identify, during total knee arthroplasty surgery, the effect on patellar kinematics of different patellar component designs in the same patients.MethodsThis study enrolled 84 patients with osteoarthritis. Intraoperative X-rays were used to measure internal rotation angle, flexion angle and lateral tilt were at different knee flexion angles with dome-type or anatomic-type patellar components (ATTUNE®, DePuy).ResultsSignificant differences from baseline between the two types of components occurred at 120° of the knee flexion in the internal rotation angle, at 90° and 120° of the knee flexion in the flexion angle, and at 60° of the knee flexion in the lateral tilt.ConclusionThis study revealed that the difference in patellar component design affects patellar kinematics. Therefore, the difference in patellar component design may affect patellar stability.