Authorship：Lead author   Language：English   Publisher：Scientific Reports  

Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA.

DOI： 10.1038/s41598-019-57073-8

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Authorship：Lead author   Language：English   Publisher：International Journal of Rheumatic Diseases  

Objective: Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add-on TAC therapy in RA patients with inadequate response to ABT. Methods: Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add-on TAC therapy and were followed for longer than 24 weeks were included in this study. Results: Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add-on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints – erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan-Meier analysis. Only one patient discontinued add-on TAC therapy due to an adverse event (itching sensation). Conclusion: This is the first report describing the efficacy and safety profile of add-on TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add-on TAC therapy is a worthwhile complementary treatment option in daily clinical practice.

DOI： 10.1111/1756-185X.13731

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Language：English  

DOI： 10.1093/mr/roae065

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Authorship：Lead author   Language：English  

DOI： 10.1093/mr/roae078

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Authorship：Corresponding author   Language：English   Publisher：International Journal of Rheumatic Diseases  

DOI： 10.1111/1756-185X.15321

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Language：English   Publisher：Journal of Orthopaedic Science  

Objective: Ankylosing spondylitis (AS) is a progressive inflammatory disease that affects the axial skeleton, and often associated with hip involvement. However, the causative factors for radiological hip involvement in patients with AS are not well characterized. This study aimed to investigate the factors associated with hip involvement in patients with AS. Methods: Sixty-seven patients (134 hips) diagnosed with AS who qualified the modified New York criteria at our institution between January 2005 and June 2022 were enrolled. Patients were divided into two groups: the hip involvement group (BASRI-hip score ≥2 points) and the normal group (BASRI-hip score <2 points). Demographic, clinical and radiographic characteristics were compared between the two groups. Results: Twenty-six patients (38.8%) had radiological hip involvement, of which 23 (88.5%) patients were male. There were significant between-group differences with respect to sacroiliac joint fusion, crossover sign, high centre edge angle and low sharp angle (P < 0.05). On logistic regression analysis, older age, sacroiliac joint fusion and pincer type were identified as independent risk factors for hip involvement. Conclusion: AS with hip involvement was significantly more likely to involve sacroiliac joint fusion, which suggested that mechanical stress in adjacent joints and reduced spinopelvic range of motion may influence hip involvement.

DOI： 10.1016/j.jos.2023.06.012

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Language：English   Publisher：Modern Rheumatology  

Objectives: To examine intervertebral fusion sites along the whole spine of patients with ankylosing spondylitis using computed tomography. Methods: This retrospective study examined intervertebral fusion of five sites (anterior/posterior vertebrae, left/right zygapophyseal joints, and spinous process) on 23 vertebrae in the cervical, thoracic, and lumbar regions of the spine in 40 patients diagnosed with ankylosing spondylitis at our institute between January 2004 and December 2022. Results: Mean age [± standard deviation (SD)] was 40.5 (± 17) years, and mean disease duration (± SD) was 11.4 (± 10.5) years at computed tomography evaluation; 55.9% were human leukocyte antigen B-27-positive. Fifteen (37.5%) patients showed intervertebral fusion in the thoracic and/or cervical regions, but not in the lumbar region. Fusion of posterior vertebrae was observed most frequently in the thoracic region, compared to the cervical and lumbar regions. In particular, more than half of the patients showed fusion of posterior vertebrae Th4-Th5 to Th7-Th8. Conclusions: In 37.5% of patients, intervertebral fusion was evident in the thoracic and/or cervical regions but not in the lumbar region. The most common site and region of intervertebral fusion were the posterior vertebrae of the middle thoracic region.

DOI： 10.1093/mr/road065

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Language：English   Publisher：Modern Rheumatology  

Objective: To compare the effectiveness of methotrexate (MTX) as initial therapy in patients with late-onset and younger-onset rheumatoid arthritis (LORA and YORA). Methods: Of 114 patients with YORA and 96 patients with LORA, defined as RA occurring at ≥65 years of age, enrolled in a multicentre RA inception cohort study, 71 and 66 patients who had been followed up to 6 months after starting MTX treatment were included in this study. Results: Proportions of patients on MTX treatment at 6 months were 96% and 92% in the YORA and LORA groups, respectively. Despite lower doses of MTX in the LORA group compared with the YORA group, no significant difference was observed in clinical disease activity index scores between the two groups throughout the follow-up period. The proportion of patients in clinical disease activity index remission at 6 months was 35% in both groups. Logistic regression analysis revealed that knee joint involvement and high Health Assessment Questionnaire-Disability Index were significant negative predictors of achieving clinical disease activity index remission at 6 months in the LORA group. Conclusion: Observations up to 6 months revealed that the effectiveness of MTX administered based on rheumatologist discretion in patients with LORA is comparable to that in patients with YORA in clinical settings.

DOI： 10.1093/mr/roae027

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Language：English   Publisher：Journal of Orthopaedic Science  

Objectives: To investigate factors predicting frailty for one year in pre-frail patients with rheumatoid arthritis (RA). Method: A total of 298 RA patients who were pre-frail in 2020 were evaluated in this structured, retrospective observational study. Of the 298 patients, 42 who were frail and 256 who were not in 2021 were assigned to the frailty and non-frailty groups, respectively. After comparing characteristics of both groups using univariate analysis, predictive factors of frailty were assessed by logistic regression analysis. The proportion of frail patients in 2021 by DAS28-ESR level in 2020 was examined by the Cochran-Armitage trend test and chi-squared test. After dividing pre-frail patients into those with DAS28-ESR ≥3.2 and DAS28-ESR <3.2 in 2020, one-year change in DAS28-ESR in the frailty and non-frailty groups for both subgroups were compared by the paired t-test. Results: The frailty group was older (mean: 71.0 vs. 65.4 years) and had a higher DAS28-ESR (mean: 3.22 vs. 2.70) than the non-frailty group. DAS28-ESR was identified as a predictive factor for frailty (OR: 1.49). Among patients with DAS28-ESR ≥3.2 in 2020, DAS28-ESR improved in the non-frailty group in 2021 (mean: 3.97 in 2020 vs. 3.13 in 2021) but did not in the frailty group (3.97 in 2020 vs. 3.81 in 2021). Among those with DAS28-ESR <3.2 in 2020, DAS28-ESR was unchanged in the non-frailty group in 2021 (2.15 in 2020 vs. 2.23 in 2021) but increased in the frailty group (2.53 in 2020 vs. 3.23 in 2021). Conclusions: Disease activity at baseline is an independent predictor of frailty one year later in pre-frail patients with RA.

DOI： 10.1016/j.jos.2022.10.025

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Authorship：Corresponding author   Language：English   Publisher：International Journal of Rheumatic Diseases  

DOI： 10.1111/1756-185X.14947

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Language：English   Publisher：International Journal of Rheumatic Diseases  

Objectives: To investigate a plateau in treatment enhancement for improving the frailty status of rheumatoid arthritis (RA) patients. Methods: A total of 345 RA patients who were not robust in 2021 were assigned to the improved (“robust 2022,” n = 51) and non-improved (“pre-frailty/frailty 2022,” n = 294) groups. Factors associated with “robust 2022” were examined by logistic regression analysis. Patients were assigned to the stable (Follow-up mean DAS28-ESR in 2020 and 2021 < 3.2, n = 225) and unstable (≥3.2, n = 120) groups, which were further divided into the non-improved (stable: n = 180, unstable: n = 114) and improved (stable: n = 45, unstable: n = 6) groups. Factors influencing Japanese Cardiovascular Health Study (J-CHS) score were examined by multiple regression analysis. Changes over 2 years were compared between the non-improved and improved groups of the stable group. Results: The associated factor of “robust 2022” was the follow-up meanDAS28-ESR in 2020 and 2021 < 3.2 (i.e., stable state) (OR: 4.01). Follow-up mean DAS28-ESR in 2020 and 2021 was associated with J-CHS score (T = 2.536, p =.013) only in the unstable group. In the stable group, HAQ-DI was lower (2020: 0.32 vs. 0.16; 2021: 0.32 vs. 0.17; 2022: 0.32 vs. 0.21), and the proportion of J-CHS: Q4 (weakness) was lower (2020: 48.4 vs. 17.8%; 2021: 55.0 vs. 29.2%; 2022: 50.4 vs. 0%), in the improved group than in the non-improved group, whereas both groups maintained clinical and functional remission over 2 years. Conclusions: Drug treatment to maintain well-controlled disease activity alone is insufficient for improving patients' frailty status after achieving treat-to-target goals, suggesting the need for multifaceted approaches.

DOI： 10.1111/1756-185X.14946

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Language：English   Publisher：Journal of Orthopaedic Science  

Background: Staphylococcus aureus (S. aureus) nasal carriage is a well-known risk factor for surgical site infection (SSI) after total joint arthroplasty. This study aimed to compare the prevalence of S. aureus nasal carriage between patients with osteoarthritis (OA), a degenerative joint disease, and those with rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, who underwent total joint arthroplasty, and to investigate the influence of RA disease activity on nasal carriage rate. Methods: This retrospective study targeted 508 OA and 107 RA patients who underwent S. aureus nasal screening prior to primary total knee and/or hip arthroplasty. RA patients were divided into two groups based on disease activity: the remission/low disease activity (REM/LDA) group and the moderate/high disease activity (MDA/HDA) group. Factors associated with S. aureus nasal carriage were assessed with multivariate logistic regression models. Results: Of all 615 patients, 155 (25%) carried S. aureus in their nares. Compared to OA patients, RA patients had a significantly higher rate of S. aureus nasal carriage (24% vs. 33%, p = 0.049). Compared to the REM/LDA group (n = 39), the MDA/HDA group (n = 58) had a significantly higher rate of S. aureus nasal carriage (21% vs. 41%, p = 0.032). Multivariate analysis revealed that the MDA/HDA group, but not the REM/LDA group, had a significantly higher odds of S. aureus nasal carriage compared to the OA group (odds ratio: 2.76, 95% confidence interval: 1.07–7.12). Conclusion: Preoperative nasal screening for S. aureus is beneficial, especially in RA patients with moderate/high disease activity.

DOI： 10.1016/j.jos.2022.09.014

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Publisher：南江堂  

DOI： 10.15106/j_besei84_158

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Language：English   Publisher：Modern Rheumatology  

Objectives: Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. Methods: The study included 564 patients with RA who started bDMARDs treatment before 2008 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models. Results: Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3-4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07-6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years. Conclusions: Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

DOI： 10.1093/mr/roac090

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Language：English   Publisher：Clinical Rheumatology  

Introduction: Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). Frailty is the intermediate condition between being healthy and disabled, and can lead to negative health outcomes. Adverse events (AEs) due to RA drugs are expected to be higher in frail patients. The present study aimed to investigate the relationship between frailty and MTX discontinuation due to AEs in RA patients. Methods: Of 538 RA patients who visited us between June and August 2020 as part of the retrospective T-FLAG study, 323 used MTX. After 2 years of follow-up, we investigated AEs leading to MTX discontinuation. Frailty was defined as a Kihon Checklist (KCL) score ≥ 8. Cox proportional hazards regression analysis was performed to identify factors associated with MTX discontinuation due to AEs. Results: Of the 323 RA patients (251 women, 77.7%) who used MTX, 24 (7.4%) discontinued MTX due to AEs during the 2-year follow-up period. Mean ages in the MTX continuation/discontinuation groups were 64.5 ± 13.9/68.5 ± 11.7 years (p = 0.169), Clinical Disease Activity Index was 5.6 ± 7.3/6.2 ± 6.0 (p = 0.695); KCL was 5.9 ± 4.1/9.0 ± 4.9 points (p < 0.001); and the proportion of frailty was 31.8%/58.3% (p = 0.012). MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02–5.37) even after adjusting for age and diabetes mellitus. AEs included liver dysfunction (25.0%), pneumonia (20.8%), and renal dysfunction (12.5%). Conclusions: Because frailty is a significant factor contributing to MTX discontinuation due to AEs, the latter should be carefully monitored in frail RA patients who use MTX. Key Points • Of the 323 rheumatoid arthritis (RA) patients (251 women, 77.7%) who used methotrexate (MTX), 24 (7.4%) discontinued MTX due to adverse events (AEs) during the 2-year follow-up period.• MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02–5.37) even after adjusting for age and diabetes mellitus, and neither the MTX dose, folic acid supplementation, nor GC co-therapy were factors in MTX discontinuation.• Frailty is a predominant factor in MTX discontinuation among established, long-term pretreated RA patients, and the occurrence of AEs due to MTX should be carefully monitored when frail RA patients use MTX.

DOI： 10.1007/s10067-023-06639-z

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Language：English   Publisher：Modern Rheumatology  

Objectives: To examine the age at onset and initial symptoms as clinical features of ankylosing spondylitis in Japanese patients. Methods: This retrospective study included 60 Japanese patients diagnosed with ankylosing spondylitis at our institute between January 2004 and June 2021. Initial symptoms were considered pain in axial joints and/or extra-axial joints. If a patient had initial symptoms at multiple sites, each site was counted. We assessed trends for the number of patients and sites of initial symptoms according to age at onset. Results: Mean age (± standard deviation) at onset was 28.9 (± 14.3) years. Approximately one-third of patients experienced onset before age 20. The back was the most common site of initial symptoms (36.7%), followed by the hip (26.7%), knee (15%), buttocks (15%), neck (10%), finger (6.7%), shoulder (3.3%), and others (including overlapping sites). Thirty-two (53.3%) and 25 (41.7%) patients had initial symptoms only in axial joints and only in extra-axial joints, respectively. The proportion of patients with initial symptoms only in extra-axial joints significantly decreased with increasing age (p =. 024). Conclusions: Sites of initial symptoms were frequently the back, hip, knee, and buttocks, and 41.7% had initial symptoms only in extra-axial joints. Younger onset patients frequently had extra-axial involvement.

DOI： 10.1093/mr/roac081

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Language：English   Publisher：Modern Rheumatology Case Reports  

Total elbow arthroplasty (TEA) is a surgical option for patients with rheumatoid arthritis (RA). Periprosthetic fractures during and after TEA are one of the most common causes of reoperation. Fractures around the stem of a loose prosthesis with associated bone loss are the most technically challenging to treat. Previous reports have demonstrated that the use of massive allografts is a reasonable alternative in salvage situations. Here, we report the case of a 78-year-old woman with RA who underwent revision TEA using massive allografts with modifications to the methods described in previous reports. She suffered a right periprosthetic humeral fracture 5 years after primary TEA, with a fracture in the proximal humeral diaphysis and a long spiral fracture in the diaphysis. The fracture around the stem of a loose prosthesis was associated with bone loss. We performed revision TEA using an allograft of the proximal femoral diaphysis. In contrast to previous reports, we preserved part of the humeral diaphysis, which was thin due to osteolysis, without removal. The advantage of this approach was that it preserved attachments, such as the deltoid and brachioradialis muscles. The patient had good elbow function and minimal pain without adverse events at 1 year postoperatively. Our findings suggest that preserving part of a thinned humeral diaphysis is a reasonable option in revision TEA with a massive composite allograft.

DOI： 10.1093/mrcr/rxad001

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Language：English   Publisher：Modern rheumatology  

OBJECTIVES: The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. METHODS: 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. RESULTS: Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23-0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30-0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. CONCLUSIONS: Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

DOI： 10.1093/mr/roac025

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Language：English   Publisher：Modern rheumatology  

OBJECTIVES: To investigate factors associated with frailty in rheumatoid arthritis (RA) patients with decreased renal function. METHODS: RA patients who visited outpatient clinics from June to August 2021 were included (N = 625). Patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 were defined as having decreased renal function (N = 221) and divided into the non-frailty (N = 153) and frailty (N = 58) groups. Patient characteristics were compared between the two groups by univariate analysis. Significant factors in univariate analysis were assessed by logistic regression analysis to determine their association with frailty in patients with decreased renal function. RESULTS: Patients in the frailty group were older (74.0 vs.79.0 years) and had a longer duration of disease (11.1 vs. 17.8 years), higher Disease Activity Score erythrocyte sedimentation rate (DAS28-ESR; 2.99 vs. 3.80), higher Health Assessment Questionnaire Disability Index (0.42 vs. 1.43), and a lower rate of methotrexate (MTX) use (46.4% vs. 25.9) compared to those in the non-frailty group. Factors associated with frailty in patients with decreased renal function were age (odds ratio: 1.07), duration of disease (1.06), DAS28-ESR (1.85), and MTX use (0.42). CONCLUSIONS: Among factors associated with frailty in RA patients with decreased renal function, improving DAS28-ESR is likely to be the most feasible approach to promote recovery from frailty (200/200 words).

DOI： 10.1093/mr/roac018

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Language：English   Publisher：Modern Rheumatology Case Reports  

We report a case of isolated lesions of the thoracic spine attributed to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A 55-year-old woman who suffered from 6 months of back pain had vertebral osteomyelitis on magnetic resonance imaging (MRI). There were no laboratory findings suggestive of infection, malignancy, or autoimmune disease. Radiography, computed tomography (CT), and MRI of the thoracic spine showed mixed lesions of sclerosis and erosion, whereas bone scintigraphy did not show accumulation at any site except the thoracic spine. No lesions in the anterior chest wall or sacroiliac joints were apparent from CT and MRI. No lesions other than at the thoracic spine were observed. As the isolated lesions of the thoracic spine were considered not to have resulted from infection, malignancy, or autoimmune disease, the patient was referred to our department for differential diagnosis. Given that isolated sterile hyperostosis/osteitis among adults is included in the modified diagnostic criteria for SAPHO syndrome, we suspected that the mixed lesions of sclerosis and erosion of the thoracic spine in this case may reflect SAPHO syndrome with chronic non-bacterial osteitis (CNO) of the thoracic spine. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated and led to alleviation of her back pain, although the thoracic spine lesions remained on the 6-month MRI. Based on the CNO of the thoracic spine and the rapid response to NSAIDs, the final diagnosis was SAPHO syndrome with isolated lesions of the thoracic spine.

DOI： 10.1093/mrcr/rxac030

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Language：English   Publisher：Journal of Orthopaedic Science  

Background: This study aimed to investigate factors associated with frailty in rheumatoid arthritis (RA) patients. Methods: A total of 656 RA patients were evaluated using data from an observational study in 2022. Among these patients, 152 with frailty were assigned to the frailty group, and 504 without frailty were assigned to the non-frailty group. Patient characteristics were compared between the two groups by univariate analysis, and factors associated with frailty were assessed by logistic regression analysis. Patient characteristics were also compared between patients with RA-associated interstitial lung disease (RA-ILD) (n = 102) and those without RA-ILD (n = 554). Results: The frailty group was older (mean: 73.6 vs. 66.8 years) and had a higher DAS28-ESR (3.67 vs. 2.66), a higher HAQ-DI (1.13 vs. 0.32), and a higher rate of RA-ILD (25.0 vs. 12.7 %) than the non-frailty group. Age (OR: 1.03, 95 % CI: 1.01–1.05), HAQ-DI (3.22, 2.28–4.56), DAS28-ESR (1.44, 1.19–1.75), and RA-ILD (2.21, 1.24–3.94) were associated with frailty. RA patients with RA-ILD were older (73.3 vs. 67.5 years) and had a higher DAS28-ESR (3.30 vs. 2.80), a higher HAQ-DI (1.19 vs. 0.32), a higher proportion of frail patients (37.3 vs. 20.6 %), lower MTX use (26.5 vs. 62.9 %), and higher steroid use (44.1 vs. 26.8 %) than those without RA-ILD. Conclusions: Maintaining reasonable control of disease activity is necessary for RA patients, including those with RA-ILD, to recover from frailty.

DOI： 10.1016/j.jos.2023.11.012

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Language：English   Publisher：Scientific Reports  

Rheumatoid arthritis (RA) patients often exhibit finger/wrist joint symptoms and reduced grip strength. This study aimed to validate grip strength as a measure of frailty in RA patients. Subjects were 424 female RA patients (mean age ± standard deviation, 66.8 ± 14.5 years). Frailty was defined as a score of ≥ 8 points on the Kihon Checklist (KCL). Finger/wrist joint symptoms were defined based on tender or swollen joints. Associations between frailty and grip strength were determined using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis. There were 179 subjects with frailty (42.2%). Multivariable logistic regression analysis revealed that frailty was significantly associated with grip strength independently of finger/wrist joint symptoms. In ROC curves, cut-off scores of grip strength for frailty in subjects without and with finger/wrist joint symptoms were 17 kg (sensitivity, 62.1%; specificity, 69.0%) and 14 kg (sensitivity, 63.2%; specificity, 73.0%), respectively. The results of the present study suggest that grip strength in female RA patients is associated with frailty, with a cut-off score of 17 kg (equivalent to Cardiovascular Health Study criteria, < 18 kg) when RA patients have no finger/wrist joint symptoms. However, when RA patients have finger/wrist joint symptoms, it may be considered to reduce the cut-off score of grip strength.

DOI： 10.1038/s41598-022-21533-5

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Language：English   Publisher：Nagoya Journal of Medical Science  

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories “GLFS-5” and “Social activities” were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in “Social activities” and that of “GLFS-5.” Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00–1.22]) and CDAI (OR: 1.08 [95%CI: 1.00–1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

DOI： 10.18999/nagjms.84.4.799

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Language：English   Publisher：Geriatrics and Gerontology International  

DOI： 10.1111/ggi.14475

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Language：English   Publisher：Nagoya Journal of Medical Science  

This study aimed to investigate changes in and factors associated with perioperative serum C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) in the biologic era. A total of 173 patients (228 knees) with RA underwent elective primary TKA at our institute between January 1, 2006 and December 31, 2018. Of these, 214 cases among 161 patients were examined in this retrospective study after excluding 3cases among 3 patients who developed postoperative complications and 11 cases among 9 patients who were treated with tocilizumab. Factors associated with changes in CRP levels between baseline (preoperative) and day 7 after TKA [∆CRP (0–7days)] were assessed by multiple regression analysis. Median (interquartile range) CRP levels were 0.69 (0.21, 1.82) mg/dl preoperatively, 5.66 (4.21, 7.61) mg/dl on postoperative day 1, 12.75 (9.79, 16.74) mg/dl on postoperative days 3–4, 3.26 (2.21, 4.85) mg/dl on postoperative day 7, and 0.87 (0.45, 1.81) mg/dl on postoperative day 14. Multivariate regression analysis revealed that body mass index ≥25 [partial regression coefficient (B)=1.03, P=0.012] and use of glucocorticoids (B=–0.86, P=0.017) were independently associated with ∆CRP (0–7days), whereas use of methotrexate and targeted drug modifying antirheumatic drugs and preoperative CRP levels (an objective biomarker of RA activity) were not. In conclusion, serum CRP levels increased rapidly after TKA and peaked on postoperative days 3–4, followed by a return to preoperative levels by postoperative day 14 in patients with RA. Obesity and the use of glucocorticoids were independently associated with changes in CRP levels.

DOI： 10.18999/nagjms.84.2.286

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Language：English   Publisher：Modern Rheumatology  

Objectives: We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms. Methods: We enrolled RA patients aged 40-79 years who visited university hospitals' outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis. Results: This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence. Conclusions: Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive.

DOI： 10.1093/mr/roab001

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Language：English   Publisher：Modern Rheumatology  

Objectives: This study aimed to evaluate the association between locomotive syndrome (LS) and frailty in rheumatoid arthritis (RA) patients. Methods: Subjects were 538 RA patients (female, 72.9%; mean age ± standard deviation, 66.8 ± 13.4 years). LS and frailty were defined as ≥16 points on the 25-question Geriatric Locomotive Function Scale (Stage ≥2) and ≥8 points on the Kihon Checklist (KCL), respectively. Results: There were 214 subjects with Stage ≥2 LS (39.8%) and 213 subjects with frailty (39.6%). Among subjects with Stage 0, 1, 2, and 3 LS, 11.0%, 21.9%, 48.3%, and 84.6% had frailty, respectively. The KCL points for cognitive and psychosocial factors had no significant differences across LS stages. Multivariable logistic regression analysis revealed that the Health Assessment Questionnaire was independently associated with frailty and LS stage, and the Clinical Disease Activity Index was associated with LS stage but not frailty. Conclusions: As LS worsens in RA patients, the likelihood of developing physical frailty increases. RA patients with a low LS stage can still develop frailty, and suppressing disease activity may not be sufficient to prevent frailty. These findings highlight the need to screen for frailty in RA patients and consider appropriate interventions based on each patient's condition, focusing on nonphysical factors.

DOI： 10.1093/mr/roab024

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Language：English   Publisher：Modern Rheumatology  

Objectives: To investigate the clinical and psychosocial backgrounds of frailty in rheumatoid arthritis (RA) patients. Methods: Patients with RA between 40 and 79 years of age who visited university hospitals in an urban area were recruited. Well-validated self-reported questionnaires were used to evaluate patient physical function (Health Assessment Questionnaire, HAQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), and frailty (Kihon Checklist). A 28-point Disease Activity Score (DAS-28) was calculated to evaluate RA disease activity. Results: A total of 375 RA patients, 323 of whom were women, were enrolled (average age: 65.2 ± 9.7 years; average disease duration: 16.6 ± 11.9 years). The prevalence rates of frailty, working-age (40–64 years), young-old (65–74 years), and old-old (≥75 years) patients were 18.5, 28.8, and 36.6%, respectively. Higher age and longer disease duration were associated with frailty. Multivariable logistic regression analysis revealed that HAQ, DAS-28, and BDI-II scores were independently associated with frailty in RA patients. Conclusion: Frailty is common, even among working-age RA patients. Physical function, disease activity, and depressive symptoms were independently associated with frailty. A multidisciplinary intervention approach, along with adequate pharmacological therapy, may promote successful aging in patients with RA.

DOI： 10.1080/14397595.2020.1838402

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Language：English   Publisher：Clinical Rheumatology  

Objective: This study aimed to compare the effects of baricitinib, a Janus kinase inhibitor, and tocilizumab, a monoclonal anti-interleukin-6 receptor antibody, on disease activity in patients with rheumatoid arthritis (RA), and to investigate the influence of inflammation on improvement in patient global assessment (PGA) of disease activity. Methods: This study was performed based on data from a multicenter registry, and included 284 and 113 patients treated with tocilizumab and baricitinib, respectively, who were observed for longer than 24 weeks. Propensity score matching was performed to address potential treatment-selection bias. To assess the influence of inflammation on PGA, patients were divided into two groups based on whether or not they achieved improvement in C-reactive protein (CRP, an objective marker of inflammation) at 24 weeks. Results: A total of 48 matched pairs of patients were identified. Compared to treatment with tocilizumab, baricitinib showed a similar improvement in tender and swollen joint count and serum CRP levels, and a significantly greater improvement in PGA at 24 weeks. As a result, the baricitinib group had a significantly higher proportion of patients who achieved Boolean remission at 24 weeks. In subgroups of patients who did not achieve 50% or 70% CRP improvement, significant decreases from baseline to 24 weeks were observed in PGA in patients treated with baricitinib, but not in those treated with tocilizumab. Conclusion: Compared to tocilizumab, baricitinib significantly improved PGA despite similar effects on inflammation in patients with RA. Moreover, the influence of inflammation on PGA improvement differed between baricitinib and tocilizumab.Key-points• Baricitinib and tocilizumab had similar effects on inflammation in RA patients.• Baricitinib improved patient global assessment (PGA) more than tocilizumab.• Baricitinib had a higher Boolean remission rate than tocilizumab at 24 weeks.• Influence of inflammation on PGA improvement differed between the two drugs.

DOI： 10.1007/s10067-021-05815-3

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Language：English   Publisher：Scientific Reports  

Transient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca2+ signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV4 activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.

DOI： 10.1038/s41598-021-94938-3

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Language：English   Publisher：Modern Rheumatology  

Objective: This study aimed to longitudinally evaluate the association between rheumatoid arthritis (RA) and locomotive syndrome (LS) in RA patients using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Methods: Subjects were 58 RA patients (female, 48 (82.8%); mean age, 60.9 ± 10.9 years) who had GLFS-25 scores available for five consecutive years and who did not have LS at baseline (i.e. GLFS-25 < 16 points). Associations between DAS28-CRP and the development of LS were determined using linear regression analysis and receiver operating characteristic (ROC) curve analysis. Results: Subjects were divided into the LS group (n = 15, GLFS-25 ≥ 16 points) and non-LS group (n = 43, GLFS-25 < 16 points) based on GLFS-25 scores at the 5th year of the study period. In the LS group, DAS28-CRP worsened every year. The linear regression model adjusted for age and sex revealed that ΔGLFS-25 increased by 3.80 (95% confidence interval: 1.81–5.79) each time ΔDAS28-CRP increased by 1 (p<.001). Among patients in remission (DAS28-CRP < 2.3), 13.5% had LS. ROC curve analysis yielded a five-year mean DAS28-CRP of 1.99 (sensitivity, 86.7%; specificity, 62.8%) as the cut-off point for the development of LS. Conclusion: Tight control of RA disease activity for deeper remission may be needed to prevent the development of LS.

DOI： 10.1080/14397595.2020.1744828

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Language：English   Publisher：Scientific Reports  

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

DOI： 10.1038/s41598-020-78925-8

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Language：English   Publisher：Joint Bone Spine  

Objective: To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Methods: Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12 weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score > 10 or intervention with rescue treatments for any reason even if the CDAI score was ≤ 10. The impact of baseline characteristics on disease flare at week 64 (52 weeks after methotrexate discontinuation) was assessed with logistic regression models. Results: Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6–81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4 weeks, or subcutaneously every 2 weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80–115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72–83.80) were independent predictors of disease flare. Conclusion: Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. Trial registration number: jRCTs041180071, UMIN000021247.

DOI： 10.1016/j.jbspin.2020.06.001

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Language：English   Publisher：Scientific Reports  

This study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. ‘ACPA positive’ was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan–Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.

DOI： 10.1038/s41598-020-76842-4

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Language：English   Publisher：Clinical Rheumatology  

Objective: Periarticular osteophyte formation is observed during the repair of damaged joints in rheumatoid arthritis (RA); however, little is known about its clinical and functional roles. This study aimed to determine the influence of periarticular osteophyte formation on the incidence of total knee arthroplasty (TKA) (a surrogate for long-term outcomes of joint destruction) in patients with RA. Methods: This retrospective longitudinal study included a total of 130 symptomatic (tender and/or swollen) knee joints in 80 patients starting biologics. Cumulative incidences of TKA were compared according to the presence or absence of osteophyte on plain anteroposterior radiograph (osteophyte (±)) and the extent of advanced joint damage as defined by Larsen’s grading system (0–II vs. III–V). Results: Kaplan-Meier estimates showed a significantly lower cumulative incidence of TKA for the osteophyte (+) group (n = 33) compared with the osteophyte (−) group (n = 31) in the Larsen grades III–V group (38 vs. 74% at 10 years, P = 0.010), whereas no significant difference was observed between the osteophyte (+) (n = 11) and osteophyte (−) (n = 55) groups in the Larsen grades 0–II group (9 vs. 10% at 10 years). Multivariate Cox proportional hazards analysis revealed that older age (hazard ratio (HR), 1.04 per 1 year; 95% confidence interval (CI), 1.01–1.08) and osteophyte formation (HR, 0.39; 95% CI, 0.19–0.79) independently predicted TKA in the Larsen grades III–V group, whereas none of the assessed variables predicted TKA in the Larsen grades 0–II group. Conclusion: Osteophyte formation reduces the incidence of TKA in patients with RA who have advanced joint damage.Key Points• Older age and Larsen grade were independent predictors of total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients.• Periarticular osteophyte formation reduced the incidence of TKA in RA patients with Larsen grades III–V.

DOI： 10.1007/s10067-020-05140-1

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Language：English   Publisher：Modern Rheumatology  

Objectives: To examine time trends in the characteristics of patients with rheumatoid arthritis (RA) undergoing primary total joint replacement (TJR). Methods: Biologics were approved in Japan for use in patients with RA in July 2003. A total of 403 large joints in 282 patients who underwent TJR at our institute between 1 January 2004 and 31 December 2017 were retrospectively examined. Results: A significant decreasing trend was observed in the number of TJRs performed from 2004 to 2017 (p = 0.013). No significant trend was observed in time from RA onset to TJR (p = 0.294). Age at RA onset (p = 0.034) showed a significant increasing trend, and serum C-reactive protein (CRP) levels showed a significant decreasing trend (p < 0.001). Negative CRP (defined as ≤0.3 mg/dl; partial regression coefficient (B) = 2.44, p = 0.016) was independently associated with time from RA onset to TJR as well as age at RA onset and juxta-articular osteophyte formation. Conclusion: The number of TJRs decreased since the approval of biologics in Japan, and changes were observed in the characteristics of patients with RA undergoing TJR. Negative CRP was an independent factor associated with longer time from RA onset to TJR.

DOI： 10.1080/14397595.2019.1649111

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Language：English   Publisher：Modern Rheumatology  

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX. Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36. Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1–18.4%; p= .025). Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.

DOI： 10.1080/14397595.2019.1641934

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Language：English   Publisher：Scientific Reports  

CD44 fragmentation is enhanced in chondrocytes of osteoarthritis (OA) patients. We hypothesized that mechanical stress-induced enhancement of CD44-intracellular domain (CD44-ICD) production plays an important role in the de-differentiation of chondrocytes and OA. This study aimed to assess the relationship between CD44-ICD and chondrocyte gene expression. Monolayer cultured primary bovine articular chondrocytes (BACs) were subjected to cyclic tensile strain (CTS) loading. ADAM10 inhibitor (GI254023X) and γ-secretase inhibitor (DAPT) were used to inhibit CD44 cleavage. In overexpression experiments, BACs were electroporated with a plasmid encoding CD44-ICD. CTS loading increased the expression of ADAM10 and subsequent CD44 cleavage, while decreasing the expression of SOX9, aggrecan, and type 2 collagen (COL2). Overexpression of CD44-ICD also resulted in decreased expression of these chondrocyte genes. Both GI254023X and DAPT reduced the production of CD44-ICD upon CTS loading, and significantly rescued the reduction of SOX9 expression by CTS loading. Chemical inhibition of CD44-ICD production also rescued aggrecan and COL2 expression following CTS loading. Our findings suggest that CD44-ICD is closely associated with the de-differentiation of chondrocytes. Excessive mechanical stress loading promoted the de-differentiation of BACs by enhancing CD44 cleavage and CD44-ICD production. Suppression of CD44 cleavage has potential as a novel treatment strategy for OA.

DOI： 10.1038/s41598-019-50166-4

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Language：English   Publisher：Nagoya Journal of Medical Science  

This study aimed to understand the clinical state of locomotive syndrome (LS) in patients with rheumatoid arthritis (RA) and to validate the use of the 25-question Geriatric Locomotive Function Scale (GLFS-25) in patients with RA and compare it side-by-side with the Health Assessment Questionnaire- Disability Index (HAQ-DI). Subjects were 159 patients with RA (female, 112 (70.4%); mean age, 66.2 ± 12.0 years) who consecutively visited Yokkaichi Municipal Hospital between June and August 2017. Mean disease duration was 11.4 ± 9.3 years, mean HAQ-DI score was 0.5 ± 0.7 points, and mean GLFS-25 score was 17.8 ± 19.1 points. The correlation between GLFS-25 and HAQ-DI was analyzed using Spearman's rank correlation coefficient. The cut-off point of GLFS-25 corresponding to HAQ-DI≤0.5, which represents functional remission in patients with RA, was calculated by ROC analysis. GLFS-25 and HAQ-DI were positively and strongly correlated (correlation coefficient=0.798). The cut-off point of GLFS-25 corresponding to HAQ-DI≤0.5 was 20 points (sensitivity, 81%; specificity, 90%). Thus, the cut-off point of GLFS-25 corresponding to functional remission is higher than that for developing LS (i.e., 16 points). Moreover, the proportion of patients with LS among those with HAQ-DI ≤0.5 was 17.9%. In conclusion, our findings suggest that some patients with RA in remission may have LS, as well as the need to consider appropriate interventions for such patients.

DOI： 10.18999/nagjms.81.3.453

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