Search

Objectives: Our objective was to investigate trends in the treatment of patients with late-onset rheumatoid arthritis (LORA) using data from the National Database of Rheumatic Diseases in Japan (NinJa)., Methods: Patients registered in the National Database of Rheumatic Diseases in Japan were classified according to the disease onset: at <65 years (young-onset rheumatoid arthritis); at 65-74 years (early LORA); and at ≥75 years (late LORA). Chronological changes in the treatment and disease activity were compared., Results: A total of 7178, 13,171, 15,295, and 15,943 patients were evaluated in 2010, 2013, 2016, and 2019, respectively. In all groups, the use of methotrexate gradually decreased, whereas that of biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) increased; the use of tumor necrosis factor inhibitors decreased, whereas that of non-tumor necrosis factor inhibitors increased. LORA was characterized by more single DMARD use and less methotrexate and biological/targeted synthetic DMARD use. Tumor necrosis factor inhibitors and interleukin-6 inhibitors were used less frequently, whereas abatacept was utilized more frequently in late versus early LORA. Conventional synthetic DMARD (excluding methotrexate) and glucocorticoid use was higher in late versus early LORA., Conclusions: This analysis revealed chronological changes in the treatment of LORA in Japan. Differences between early and late LORA suggest that patients are not a homogeneous population., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75-84 years) patients with rheumatoid arthritis., Methods: Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55-84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression., Results: About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64 years) and young-old patients (65-74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients., Conclusions: Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objective: The human leukocyte antigen (HLA) is the strongest genetic risk factor for idiopathic inflammatory myopathy (IIM), and different HLA alleles have been reported to be associated with IIM susceptibility among different ethnic groups. In this study, we have investigated HLA alleles associated with IIM in Japanese patients. Methods: Genotyping of HLA-DRB1 and DPB1 were performed in 252 Japanese IIM patients (166 dermatomyositis [DM] and 86 polymyositis [PM] patients) and the association was analyzed with comparison to controls ( n  = 1026 for DRB1 and n  = 413 for DPB1 ). Results: DRB1*08:03 was associated with IIM ( p  = 1.60 × 10 -5 , p c = .0005, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.52-2.92) and DM ( p  = .0004, p c = .0128, OR 2.06, 95%CI 1.40-3.02). DPB1*05:01 was also associated with IIM ( p  = .0001, p c = .0021, OR 1.96, 95%CI 1.38-2.77) and DM ( p  = .0005, p c = .0075, OR 2.05, 95%CI 1.37-3.08). DRB1*09:01 ( p  = .0012, p c = .0368, OR 0.35, 95% CI 0.18-0.69) and DPB1*04:01 ( p  = .0004, p c = .0057, OR 0.05, 95% CI 0.00-0.85) were protectively associated with PM. Two locus analyses suggested that DRB1*09:01 and DPB1*04:01 were independently associated with PM. Conclusion: Protective associations of HLA were detected in Japanese PM patients.

Objectives: Interstitial lung disease (ILD) is a life-threatening extra-articular manifestation of rheumatoid arthritis (RA). We aimed to clarify the relationship between chronic ILD with a pattern of usual interstitial pneumonia (UIP) or non-UIP and mortality in RA patients. Methods: We retrospectively surveyed information of consecutive RA patients who visited our hospital from 2009 to 2014. The relationship between their mortality and chronic ILD (UIP or non-UIP) detected by high-resolution computed tomography was examined. Results: Of 2702 patients enrolled, 261 (9.7%) had chronic ILD and among these 120 had a UIP pattern. At the onset of RA, the prevalence of chronic ILD was 6%. Patients with chronic ILD had a higher mortality than those without. The most frequent cause of death was pneumonia including acute exacerbation (AE) of chronic ILD. Lung cancer death was frequently identified in deceased patients with chronic ILD with a UIP pattern compared with the other decedents ( p =.062). The estimated mortality of lung cancer in patients with chronic ILD with a UIP pattern was five times higher than the general population. Conclusion: RA patients with ILD with a UIP pattern have a high mortality rate and are prone to die of AE or lung cancer.

Objective: To evaluate the difference between adult juvenile idiopathic arthritis (JIA, starting at <16 years) and rheumatoid arthritis (RA). Methods: Data on 128 adult JIA patients were from the National Database of Rheumatic Diseases in Japan (NinJa), 2014, divided into 4 groups by period of disease onset (Group 1: 2000-2013, n  = 32; Group 2: 1981-1999, n  = 32; Group 3: 1966-1980, n  = 31; Group 4: ∼1965, n  = 33). Disease activity, treatment and long-term prognosis of adult JIA patients were compared with RA patients matched for sex- and disease duration in each era. Results: In Groups 1 and 2, adult JIA patients had significantly lower clinical disease activity indices (CDAI) (Group 1: adult JIA 1.5 [0.4-6.9]-vs-RA 5.3 [2.5-10.3], p  = .001, Group 2: 2.6 [0.6-9.0]-vs-6.9 [3.5-11.0], p  = .001, shown as median [quartile range], p -value, respectively), and had higher CDAI remission rates than RA patients (Group 1: 54.8%-vs-28.2%, p  = .002, Group 2: 51.7%-vs-17.0%, p  < .001). More adult JIA than RA patients in Group 1 used biologics (62.5%-vs-24.7%, p  < .001). However, there were no adult JIA-vs-RA differences in joint destruction and physical function in any group. Conclusions: Adult rheumatologists must recognize that adult JIA patients are different from RA patients even when disease duration is the same.

Objectives: To investigate the distribution of 25-question Geriatric Locomotive Function Scale (GLFS-25) scores in Japanese rheumatoid arthritis (RA) patients and evaluate relationships with clinical variables., Methods: Among 15,115 patients registered in the NinJa database for fiscal year 2015, 1710 with complete GLFS-25 and disease activity score-28 (DAS28) data were analyzed. Correlations between GLFS-25 score and clinical variables were assessed by Spearman coefficients. Mean GLFS-25 scores were compared among DAS28 groups (<2.6, 2.6-3.1, 3.2-5.0, ≥5.1) using the Kruskal-Wallis test. To evaluate the performance of the GLFS-25 and Health Assessment Questionnaire Disability Index (HAQ-DI) for predicting DAS28 ≥ 3.2 (moderate/high disease activity), receiver operator characteristic (ROC) curves were constructed., Results: GLFS-25 score was significantly correlated with age, disease duration, DAS28, and HAQ-DI. GLFS-25 score increased in parallel with DAS28. The proportion of patients with locomotive syndrome stage 2 also increased with DAS28. Area under the curve values for HAQ-DI and GLFS-25 score were 0.739 and 0.768, respectively. At a GLFS-25 positive cutoff score ≥16, sensitivity was 0.716 and specificity was 0.661 for predicting DAS28 ≥ 3.2., Conclusion: This study documents the GLFS-25 score distribution in Japanese RA patients and demonstrates that GLFS-25 is a useful measure for evaluating functional ability in RA.

Objectives: To understand the current status of adult rheumatology care for patients who had previously had juvenile idiopathic arthritis (JIA) (excluding systemic JIA), and to identify issues interfering with the transition from pediatric to adult care in Japan., Methods: Questionnaire-based survey among 30 adult rheumatologists., Results: Eighty-seven percent of adult rheumatologists responded that they had provided medical care to adults who had had JIA; 44% of them had felt hesitation or anxiety when providing such care. The reasons for this included lack of independence of the patients, lack of knowledge and experience among adult rheumatologists, and lack of preparation for accepting such patients. Many adult rheumatologists believed that the timing of transition from pediatric to adult rheumatology care must be considered based on therapeutic regimens or clinical conditions/disease states, not solely chronological age. A majority of adult rheumatologists showed great interest in transitional care for JIA patients and desired to communicate better with pediatric rheumatologists., Conclusion: Transitional care for JIA patients is not sufficiently developed in Japan. Education and advocate campaign of transitional care is required for adult rheumatologists as well as patients and their parents.

Objectives: To identify the determinant of patients' perspectives of quality of life (QOL) and working status out of analysis-derived components underlying a set of assessment measures of the status of patients with rheumatoid arthritis (RA)., Methods: From the NinJa database in Japan (2012-2014), 1455 RA patients with DAS28 > 3.2 were recruited. Components explaining RA status were derived from principal component analysis of 15 assessment measures. Multivariate regression was used to examine the relative contribution of each identified component to the EuroQOL-5 Dimension Questionnaire score and working status., Results: Among the identified components (patient symptoms, physical disability, evaluated symptoms, patient distress, inflammatory marker, and serological marker), patient distress showed highest contribution to EuroQOL for both male (44.6%) and female patients (39.3%). Physical disability was associated with significantly less participation in paid work in male (odds ratio [OR]; 0.63) and both household and paid work in female (OR; 0.82 and 0.54, respectively), though patient distress showed the strongest association with less participation in both household and paid work in female (OR; 0.64 and 0.45, respectively)., Conclusion: The approach to latent patient distress using psychological screening tools, concurrently with the treatment to control the activity of arthritis, can be help to improve health-related QOL (HRQOL) including work participation.

Objective: Nontuberculous mycobacterial (NTM) pulmonary disease is occasionally associated with rheumatoid arthritis (RA), influencing the therapeutic strategy of RA. Since chronic lung diseases are frequently associated with RA, the diagnosis of NTM pulmonary disease is quite difficult in RA patients. Recently, a serological diagnostic test detecting serum immunoglobulin A against the glycopeptidolipid (GPL) core antigen was developed. We investigated the serum levels of anti-GPL antibodies in RA patients to determine the usefulness for detecting NTM pulmonary disease., Methods: Anti-GPL antibodies were detected in the sera from RA patients with or without NTM pulmonary disease., Results: The positivity of anti-GPL antibodies in RA patients with NTM pulmonary disease was higher than in RA without (p = 1.76 × 10 -14 , odds ratio 70.29, 95% confidence interval [CI] 22.28-221.83). Anti-GPL Ab titers were increased in RA with NTM pulmonary disease (mean titer ± standard deviation [U/ml], RA with NTM pulmonary disease: 4.1 ± 7.0, RA without NTM pulmonary disease: 0.4 ± 1.6, p = 1.51 × 10 -10 ). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for anti-GPL antibodies was 0.917 (95%CI 0.860-0.974, p = 3.32 × 10 -47 )., Conclusions: Serum anti-GPL antibodies are useful for detecting NTM pulmonary disease in RA patients.

Objectives: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role of intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate the clinical characteristics and efficacy of immunosuppressive treatment in exacerbated RA-ILD., Methods: Clinical data, including respiratory function, imaging, treatment, and prognosis, were retrospectively collected for 17 patients with RA-ILD who required hospitalization at the University of Tokyo Hospital due to an acute exacerbation (12 patients) or subacute exacerbation (5 patients)., Results: Patients with RA-ILD demonstrated a significantly higher titers of anticyclic citrullinated peptide antibodies compared with RA patients in Japanese Ninja registry, suggesting the role of adaptive immunity. Immunosuppressive treatment suppressed the deterioration of pulmonary functions with improved ground grass opacity and consolidation. In particular, in patients with less fibrosis on computed tomography (CT) images showed a better response to treatment. Although five patients treated with combination therapy, including cyclophosphamide, showed a severely decreased lung volume, these intensive therapies provided a good prognosis without fatalities for the average observation period of 474 days., Conclusions: Immunosuppressive therapy is effective for exacerbations of RA-ILD. For severe cases with low respiratory function, intensive therapy, including cyclophosphamide, has a potential to improve the prognosis.

Objectives: To investigate the effect of bilateral and unilateral joint disease on the Modified Health Assessment Questionnaire (MHAQ) scores and the differences in joint weighting in rheumatoid arthritis patients., Methods: A total of 9212 subjects from the Japanese nationwide cohort database NinJa, 2011, were analyzed. The presence or absence of disease in each joint, including swelling and/or tenderness, was investigated. The correlations between bilateral and unilateral disease in each joint and MHAQ scores were investigated using multivariable logistic regression analysis., Results: The patients' mean age and disease duration was 63.2 and 12.2 years, respectively. The Disease Activity Score-28 was 3.3. The odds ratios of physical impairment according to the MHAQ using multivariable logistic regression models for bilateral and unilateral joints, respectively, were: shoulder, 4.0 and 1.8; elbow, 2.6 and 1.8; wrist, 1.9 and 1.5; hip, 1.7 and 3.0; knee, 2.6 and 1.9; ankle, 2.3 and 2.0, finger, 1.4 and 1.2; and toe, 1.0 and 1.1. The shoulder, elbow, wrist, knee, and ankle had a significant effect on physical impairment., Conclusions: The MHAQ score was significantly affected by shoulder, elbow, wrist, knee, and ankle joint disease. Furthermore, bilateral disease tended to have a greater effect on physical impairment than unilateral disease.

Objective: To evaluate the utility of quantifying CD64 expression on neutrophils in rheumatoid arthritis patients with malignancy, especially its diagnostic role in lymphoma., Methods: We used flow cytometry to quantify CD64 expression on neutrophils from patients diagnosed with malignancy during the follow-up period prior to initiating treatment., Results: Neutrophils from 18 patients with lymphoma expressed significantly higher levels of CD64 (9635.6 ± 2123.7 molecules/cell) than those from 32 patients with other solid cancers (carcinoma) (1250.5 ± 91.1 molecules/cell) (p < 0.001). When the cutoff value was set at 2060 molecules/cell, the sensitivity and specificity of CD64 for diagnosing lymphoma was 88.9% and 94.4%, respectively., Conclusions: The quantitative measurement of neutrophil CD64 by flow cytometry may be useful as a subsidiary diagnostic marker in patients with suspected lymphoma. Although neutrophil CD64 is currently a well-known marker of infection, it is necessary to bear in mind that lymphoma is also a candidate in differential diagnosis when CD64 expression on neutrophils is upregulated.

Objectives: To estimate the prevalence of chronic kidney disease in patients with rheumatoid arthritis (RA) and the administration of disease-modifying anti-rheumatic-drugs (DMARDs), using data from the National Database of Rheumatic Disease by iR-net in Japan (NinJa) 2012 study., Methods: From a total of 11,940 RA patients, 7135 who underwent an estimated glomerular filtration rate (eGFR) test were studied. Renal dysfunction staging was assessed using Japanese eGFR equations and classified according to the Kidney Disease Improving Global Outcomes 2012 clinical practice guideline., Results: The prevalence of GFR stages was as follows: stage G1, 25.4%; stage G2, 55.9%; stage G3, 17.5%; stage G4, 0.8%; and stage G5, 0.2%. Overall, 92.7% of patients received at least one DMARD. Sulfasalazine, tacrolimus, and biologics (except inflixmab) were administered in all GFR stages. Methotrexate was not prescribed in patients with stage G5, but methotrexate 3.5 mg/week (mean) was prescribed in four patients (6.8%) with stage G4. Non-steroidal anti-inflammatory drugs and glucocorticoids were prescribed in 40.5% and 43.7% of patients, respectively., Conclusion: The prevalence of kidney disease in this large sample of RA patients was higher than that in the general population, and the results suggest that RA patients with renal dysfunction require careful drug selection.

Objectives: The aim of this study was to clarify the prevalence and the predictive factors for undergoing total knee arthroplasty (TKA) among patients with rheumatoid arthritis (RA)., Methods: The data of 1,134 patients with RA who were enrolled in the Japanese nationwide cohort database NinJa in 2003 and consecutively followed up until 2009 were analyzed., Results: Seventy-six patients underwent TKA during the observation period. The yearly progression of the modified Health Assessment Questionnaire or mHAQ score from 2003 to 2004, but not the yearly progression of the Disease Activity Score in 28 Joints or DAS28 or patient visual analog scale (VAS) score, was significantly higher in the patients who underwent TKA than those who did not. Multivariate analysis showed that knee involvement in the disease, high Steinbrocker stage (III or IV), and high patient VAS score at the time of enrollment were powerful predictive factors, with hazard ratios of 4.01, 3.71, and 1.20, respectively. According to survival analysis with TKA as an endpoint, patients with knee involvement in the disease at the time of enrollment had a significantly worse 5-year survival rate than did those without knee involvement (83.5% vs. 97.0%, respectively)., Conclusion: Several factors were elucidated as predictive factors for undergoing TKA among patients with RA.

Objective: Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP., Methods: A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model., Results: A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42 patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates., Conclusion: Careful consideration of the benefit-risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.

Objectives: To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers., Methods: The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year., Results: The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups., Conclusions: This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.

Objective: To evaluate the utility of neutrophil CD64 as a marker for monitoring the activity of nontuberculous mycobacteria (NTM) infection in patients with rheumatoid arthritis (RA)., Methods: We compared neutrophil CD64 expression in nine RA patients with NTM infection in the active and inactive phase of NTM disease chronologically. "Active phase" was here defined as present in patients admitted to hospital to receive intensive treatment for NTM, as well as outpatients with an infectious episode showing positive acid- and alcohol-fast bacillus (AFB) staining of sputa (Grade 2-3) who needed to start treatment for NTM with a multiple antibiotics regimen. The cut-off value for CD64 positivity was 2000 molecules/cell., Results: Neutrophils from patients with active-phase NTM infection expressed high levels of CD64 with a mean ± SEM of 7335 ± 784 molecules/cell. However, during the inactive phase of disease, this was significantly lower (1481 ± 103 molecules/cell, p < 0.001). The sensitivity and specificity of neutrophil CD64 to detect active-phase NTM infection was 96.3% and 84.6%, respectively. Expression of neutrophil CD64 was not affected by disease activity of the RA itself., Conclusions: Neutrophil CD64 is useful for monitoring disease activity in NTM infection of patients with RA.

Objectives: To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration., Methods: Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves., Results: A total of 187 patients were eligible. At baseline of this study, median disease duration was 7.8 years, preceding TCZ treatment period was 4.0 years and DAS28 was 1.5. The rate of continued LDA at 52 weeks was 13.4 % according to the Kaplan-Meier estimate. 19 patients (10 %) were completely drug-free and 17 patients (9.1 %) fulfilled DAS28 remission at 52 weeks. Multivariate Cox regression analysis identified low serum IL-6 and normalisation of MMP-3 levels at cessation of TCZ as independent predictive markers for longer duration of LDA. In patients with low serum IL-6 (<12.9 pg/mL) and normal MMP-3 levels, the rate of continued LDA reached 38.0 % at 52 weeks., Conclusions: TCZ monotherapy may induce biologics-free remission or LDA without concomitant use of synthetic DMARDs. Serum levels of IL-6 and MMP-3 are useful markers for identifying patients who could discontinue TCZ without acute disease flare.

Objectives: To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy., Methods: Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks., Results: A total of 164 eligible patients, including 161 who experienced loss of efficacy within 52 weeks of the DREAM study, resumed treatment: 157 with TCZ and 7 with DMARDs and/or infliximab. Of TCZ-treated patients, 88.5 % (139 patients) achieved DAS28 <2.6 within 12 weeks, whereas among patients treated with DMARDs and/or infliximab only 14.3 % (1 patient) achieved DAS28 <2.6. Adverse events were observed in 70 TCZ-treated patients (44.0 %), but no serious infusion reactions were observed., Conclusions: Retreatment with TCZ was well-tolerated and effective in patients who had responded to the preceding TCZ monotherapy but had experienced loss of efficacy after cessation of TCZ.

Objective: The primary objective of this study was to evaluate the tolerability of single and multiple doses of abatacept in Japanese patients with rheumatoid arthritis. Secondary objectives included evaluating its pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy., Methods: This dose-escalation, single- and multiple-dose, multicenter, open-label study was conducted at nine sites in Japan. Seven patients were enrolled at each of three dose levels (2, 8 and 16 mg/kg) and received a single intravenous dose of abatacept on day 1 of the single-dose phase. The multiple-dose phase, at the same dose, started once the patients had completed the single-dose phase and when it was confirmed that there were no safety issues., Results: Twenty patients started the single-dose phase. Single and multiple doses of abatacept were well tolerated, and adverse events were of mild to moderate intensity. There were no discontinuations or deaths due to adverse events. The pharmacokinetics of abatacept were linear, with no notable accumulation. There were no immunogenic effects on the safety, efficacy, or pharmacokinetics of abatacept. Multiple doses of abatacept improved individual items of the American College of Rheumatology core set., Conclusion: Single and multiple doses of abatacept showed favorable tolerability and efficacy in Japanese patients with rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disorder involving multiple joints. We investigated the distribution of the affected joints and the relationships among this distribution, the disease activity, and the disease duration in Japanese RA patients by cross-sectional analysis using the National Database of Rheumatic Diseases by iR-net in Japan., Materials and Methods: A total of 6408 RA patients registered in the database were analyzed. In each patient, the location of joint swelling and joint tenderness of 68 joints was examined, and the relationships among the distribution of the affected joints, the disease activity as determined using the DAS28-ESR, and the disease duration were analyzed statistically., Results: For the 6408 RA patients examined, the wrist was the most frequently affected site. There were some differences in the prevalence of tenderness and swelling; tenderness was frequently observed in large joints such as the knee, elbow and shoulder, while swelling was frequently observed in small joints such as the metacarpophalangeal joints. Although the frequency of involvement increased in all joints as disease activity increased, the pattern of distribution was not affected by disease activity. Furthermore, the distribution was not influenced by disease duration., Conclusions: Based on the results of this study, we can draw the following conclusions: (1) the wrist was the most affected joint; (2) there was a discrepancy between the distribution of swollen joints and that of tender joints; and (3) the distribution of affected joints was uniform regardless of disease activity.

A 77-year-old woman with rheumatoid arthritis was admitted as an emergency because of pain in the right leg with purpura. She was diagnosed with severe cellulitis and sepsis and started on intravenous antibiotics; however, the lesion rapidly extended to the proximal thigh and she died only 38 h after the onset of the first symptom. Autopsy and tissue culture revealed necrotizing fasciitis caused by Streptococcus dysgalactiae subspecies equisimilis. Physicians should consider that necrotizing fasciitis may be present when soft-tissue disorder is suspected in patients receiving corticosteroid therapy, which is associated with tissue fragility and immunosuppression.

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.

The usefulness of neutrophil CD64 expression was examined in diagnosing local infection, including soft tissue, bone, and joint infections. Among 99 patients suspected of local infection, 31 were confirmed and 68 patients were not. The CD64 level of patients with local infection was significantly higher than in those without infection [4,193 ± 1,132 vs. 1,017 ± 59 molecules/cell (mean ± standard deviation); p < 0.001]. The area under the curve of CD64 calculated by receiver operating characteristic curve analysis was larger than that of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), or white blood cell (WBC) count. In addition, CD64 levels of patients with crystal-induced arthritis remained within cutoff value (2,000 molecules/cell). These data suggest that measuring CD64 expression can be a useful diagnostic marker for local musculoskeletal infection and crystal-induced arthritis.

The aim of this study was to investigate changes in the treatment strategy of rheumatoid arthritis (RA) and the prevalence of RA-related surgeries after approval of biologics in Japan and to analyze the impact of biologics on the incidence of orthopedic surgeries using a nationwide observational cohort database of rheumatic diseases [National Database of Rheumatic Diseases by iR-net in Japan (NinJa)]. The proportion of patients using biologics linearly increased from 2004 (1.8%) to 2007 (10.0%), but neither the number nor type of RA-related surgery significantly changed during this period. Patients treated with biologics exhibited relatively more severe disease activity and lower physical function. Among patients using biologics, those who underwent RA-related surgeries exhibited background characteristics of longer disease duration and worse physical function, while disease activity was not different from patients without surgery. These results suggest that the potential value of biologics in avoiding surgical procedure is limited in patients with severe functional disorders caused by long disease duration. Further investigation with a longer observation period is required to obtain more definite conclusions as to the impact of biologics usage on orthopedic surgeries.

The purpose of this study was to describe the prevalence of total joint arthroplasty (TJA) in Japanese rheumatoid arthritis (RA) patients undergoing conventional drug treatment in a large observational cohort in Japan. A total of 5,177 RA patients were studied for the prevalence of TJA, who were enrolled in the NinJa database during the fiscal year of 2006. The cases of 2,695 RA patients with more than ten years of disease duration were extracted and subjected to further analysis. The prevalence of TJA increased in accordance with the disease duration, and the prevalence was markedly increased after ten years. Among the 2,695 patients with more than ten years of disease duration, 1,431 TJAs were performed in 645 (24.6%) patients. The patients with TJA had higher disease activity than those without TJA. In this cross-sectional study, TJAs were performed in approximately a quarter of the Japanese RA patients with more than ten years of disease duration. The result showed that patients with higher disease activity required TJA.

A case of biopsy-confirmed chronic leptomeningitis complicating rheumatoid arthritis in a 53-year old female is reported. Her symptoms included weight loss, severe depression, and pyrexia. Magnetic resonance imaging was useful in diagnosis. Intravenous methylprednisolone was prescribed (1 g/day for 3 days), followed by prednisolone (initial dose of 30 mg daily), and this treatment was effective. Her IgG-index, serum levels of soluble interleukin-2 receptor and ferritin, and cerebrospinal level of interleukin-6 paralleled her clinical course.

For better management of rheumatoid arthritis (RA) patients, we need information both from well-designed clinical trials, such as randomized controlled trials, and from observational cohorts. Observational cohort study has not been developed in Japanese RA patients; however, two cohorts, IORRA (formerly J-ARAMIS) from 2000 and NinJa by iR-net from 2002, have been established. These two cohorts are an important source not only for better management of Japanese RA patients but also for solutions to a variety of issues concerning RA clinical practice in general. In this minireview, necessities of observational cohort studies are discussed.