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Abstract This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.

Abstract Background The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA. Methods Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results. Results Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway. Conclusions Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.

AbstractAbatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p = .0336 by Fisher’s exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use.

Abstract Background Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. Methods Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. Results We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. Conclusions With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.

Abstract Background Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia. Methods This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population. Discussion This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs. Trial registration The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm ) on January 4, 2022.

AbstractThe short-term effect of tocilizumab (TCZ) on the radiographic progression of rheumatoid arthritis has been reported; however, reports on its long-term effects are scarce. In this study, we aimed to evaluate its long-term effects on joint destruction in patients who had been treated with TCZ for at least two years and for whom X-rays were available. Radiographic progression was evaluated with modified Total Sharp Score (mTSS), and structural remission was defined as the mean annual change in mTSS ≤0.5. Of the 59 patients included in this study (median age, 62 years; female, 81.4%), 34 patients (57.6%) achieved structural remission. Patients who achieved structural remission were relatively younger (59 years vs. 64 years, p = .06), had relatively higher proportion of anti-citrullinated protein antibody positivity (91.2% vs. 72.0%, p = .08), relatively lower C-reactive protein level (0.6 mg/dL vs. 2.2 mg/dL, p = .05), and significantly lower erythrocyte sedimentation rate (ESR) level (28.0 mm/h vs 65.5 mm/h, p = .003) than those who did not. Multivariate logistic regression analysis demonstrated that the baseline ESR level was significantly associated with structural remission (odds ratio, 0.98; 95% confidence interval: 0.96–0.99, p = .049). The baseline ESR level is a critical determinant of the long-term effect of TCZ on joint destruction.

Abstract Background Anti-citrullinated protein/peptide antibodies (ACPAs) are present in patients at onset and have important pathogenic roles during the course of rheumatoid arthritis (RA). The characteristics of several molecules recognized by ACPA have been studied in RA, but the positivity rate of autoantibodies against each antigen is not high, and the pathogenic mechanism of each antibody is not fully understood. We investigated the role of anti-citrullinated osteopontin (anti-cit-OPN) antibodies in RA pathogenesis. Methods Enzyme-linked immunosorbent assays on RA patients’ sera were used to detect autoantibodies against OPN. Fibroblast-like synoviocytes (FLS) isolated from RA patients were used to test the binding activity and inflammatory response of OPN mediated by anti-cit-OPN antibodies, and their effect was tested using an inflammatory arthritis mouse model immunized with cit-OPN. Anti-cit-OPN antibody positivity and clinical characteristics were investigated in the patients as well. Results Using sera from 224 RA patients, anti-cit-OPN antibodies were positive in approximately 44% of RA patients, while approximately 78% of patients were positive for the cyclic citrullinated peptide (CCP2) assay. IgG from patients with anti-cit-OPN antibody increased the binding activity of OPN to FLSs, which further increased matrix metalloproteinase and interleukin-6 production in TNF-stimulated FLSs. Mice immunized with cit-OPN antibodies experienced severe arthritis. Anti-cit-OPN antibodies in RA patients decreased the drug survival rate of tumor necrosis factor (TNF) inhibitors, while it did not decrease that of CTLA4-Ig. Conclusions Anti-cit-OPN antibodies were detected in patients with RA. IgG from patients with anti-cit-OPN antibodies aggravated RA, and anti-cit-OPN antibody was a marker of reduced the survival rate of TNF inhibitors in RA patients.

Abstract Background Sotrovimab neutralizing SARS-CoV-2 remained effective at the advent of B.1 lineage of the Omicron variant in outpatients. Primarily for hospitalized patients, however, the Japanese government regulated to administer this antibody agent. As this regulation enabled close monitoring in inpatients to investigate post-infusion adverse events (AEs) and efficacy, we attempted a retrospective study while the Omicron BA.1 lineage was dominant regionally. Methods Subjects were inpatients with COVID-19 who received infusion of sotrovimab in our institute. In line with previous clinical trials, we included patients at risk of COVID-19 worsening and SARS-CoV-2 vaccinees, who were hospitalized as directed by the government. For statistical analyses, we reviewed background factors of demographics, imaging, and laboratory findings for the outcome infusion-related reactions including post-infusion pyrexia over 38 degrees Celsius and/or pulse oximetry below 94%. Results In a total of 139 patients, the follow-up period had a median of 200 days (range, 154–248 days). Among 119 patients (85.6%) fully vaccinated for SARS-CoV-2, 86 (61.9% of all) underwent 2 doses while 33 (23.7% of all) received 3 doses. For the outcome of pyrexia and/or dyspnea (N = 40, 28.8%), multivariate analysis showed that significant risk factors were pre-infusion lowered oximetry below 96.5% (Odds Ratio [OR] 0.344, 95% Confidence Interval [CI] 0.139–0.851, P = 0.021) and pre-infusion temperature more than 36.7 degrees Celsius (OR 4.056, 95% CI 1.696–9.701, P = 0.002). Infusion-related reactions included vomiting immediately after infusion, chill/shivering, dizziness, rash, pruritus, pyrexia, and dyspnea. The number of patients with any of these events was 44 (31.6%). Three patients (2.2%) showed worsening of COVID-19; one developed hypoxia and two died. Limitations for this study included no genome typing whether BA.1 or BA.2 lineage of the Omicron variant but the local epidemiology indicated the prevalence of BA.1. Another was sotrovimab administration for inpatients that allow precise detection of post-infusion events, confounding previous exacerbation definition including hospitalization. Conclusions For 24 h after infusion of sotrovimab, COVID-19 patients showing pre-infusion lowered oximetry below 96.5% and/or temperature more than 36.7 degrees Celsius may have temperature elevation or dyspnea, warranting close monitoring for these risk factors.

Abstract Background Spondyloarthritis (SpA) is an autoimmune and autoinflammatory musculoskeletal disease characterised by systemic enthesitis. Recent research has focused on subclinical inflammatory bowel disease (IBD) in SpA pathogenesis. SKG mice, harbouring the Zap70 W163C mutation, increase autoreactive Th17 cells intrinsically, and in a conventional environment, they exhibit spontaneous arthritis with fungal factors. Under SPF conditions, they show SpA features, including enteritis, after peritoneal injection of β-1,3-glucan. This study aimed to clarify whether oral dextran sulfate sodium (DSS) administration, utilised in IBD model mice, can provoke SpA features in SKG mice under SPF conditions, focusing on the relationship between gut microorganisms and SpA pathogenesis. Methods BALB/c and SKG mice were administered oral DSS, and their body weights, arthritis, and enthesitis scores were recorded. In another cohort, antibiotics (meropenem and vancomycin) or an anti-fungal agent (amphotericin B) was administered orally before DSS administration. The splenic Th1 and Th17 cell populations were examined before and after DSS administration using flow cytometry. Furthermore, the amount of circulating bacterial DNA in whole blood was measured by absolute quantitative polymerase chain reaction (qPCR), and the number and characteristics of bacterial species corresponding to these circulating DNA were analysed by next-generation sequencing (NGS). Results Ankle enthesitis as a peripheral SpA feature was elicited in half of DSS-administered SKG mice, and none of the BALB/c mice. Pre-administration of antibiotics suppressed enthesitis, whilst an anti-fungal agent could not. Th1 and Th17 cell levels in the spleen increased after DSS administration, and this was suppressed by pre-administration of antibiotics. SKG mice have a larger amount of bacterial DNA in whole blood than BALB/c mice before and 1 day after the initiation of DSS administration. The number of bacterial species in whole blood increased after DSS administration in BALB/c and SKG mice. Some genera and species significantly specific to the DSS-treated SKG mouse group were also detected. Conclusion Oral DSS administration alone elicited peripheral enthesitis in SKG mice with bacterial translocation accompanied by increased splenic Th1 and Th17 cell levels. Pre-administration of antibiotics ameliorated these DSS-induced SpA features. These findings suggest that intestinal bacterial leakage plays a pivotal role in SpA pathogenesis.

Abstract Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options.

The mature form of sterol regulatory element‐binding protein (SREBP)1 is a transcription factor involved in lipid synthesis, which participates in toll like receptor 4‐triggered inflammatory pathways during the resolution phase of inflammation in macrophages. SREBP1 has thus attracted interest as a candidate target molecule for ameliorating inflammation. Fatostatin is a small molecule that inhibits the maturation and function of SREBP, and its role in regulating inflammation is poorly understood. To evaluate the anti‐inflammatory effect of fatostatin, we compared body weight, footpad and hock dimensions, and arthritis scores between K/BxN serum‐induced arthritis mice treated with fatostatin and those treated with dimethyl sulfoxide as the vehicle control. We performed hematoxylin and eosin staining of joints of distal paws to assess tissue inflammation. Moreover, inflammatory cytokine production levels and cell viability were measured in lipopolysaccharide‐responsive human embryonic kidney 293 cells (293/hTLR4A‐MD2‐CD14 cells) after fatostatin administration. In K/BxN serum‐induced arthritis mice, fatostatin treatment significantly reduced the arthritis scores and hyperplasia. In vitro analysis revealed that fatostatin significantly inhibited the secretion of inflammatory cytokines from cells activated with lipopolysaccharide, without affecting cell viability. This is the first study to demonstrate that fatostatin is an anti‐inflammatory agent that modulates the processing of lipid transcription factors without affecting cell viability. Accordingly, the study reveals the potential of anti‐inflammatory therapeutics that link lipid regulation and inflammation.

Abstract Background Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. Main body Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060–6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026–0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599–19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. Conclusions For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Difficult-to-treat rheumatoid arthritis (D2T RA) is a multifactorial condition in which disease activity of RA persists despite consecutive treatment with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). To evaluate the prevalence and predictive risk factors of D2T RA in our institution, a single-center, retrospective study was conducted. Medical records of RA patients, who visited our hospital from 2011 to 2020 and had a follow-up of more than 6 months, were retrospectively reviewed. D2T RA was defined as RA with a disease activity score of 28 – erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or higher at the last visit, despite the use of at least two b/tsDMARDs. A logistic regression model was used to identify risk factors. A total of 672 patients were enrolled. The mean age at disease onset was 52.1 years and females were dominant (76.3%). After a mean follow-up of 46.6 months, patients with D2T RA accounted for 7.9% of overall patients. Multivariate analysis identified high rheumatoid factor (RF) levels (≥156.4 IU/mL, odds ratio [OR]: 1.95), DAS28-ESR (OR: 1.24), and coexisting pulmonary disease (OR: 2.03) as predictive risk factors of D2T RA. In conclusion, high RF levels, high DAS28-ESR, and coexisting pulmonary disease at baseline can predict the development of D2T RA.

BackgroundEstablished assessment tools for patients with rheumatoid arthritis (RA), including disease activity scores (DASs), disease activity indexes (DAIs), visual analog scales (VASs), and health assessment questionnaires (HAQs), are widely used. However, comparative associations between joint involvement and disease status assessment tools have rarely been investigated.MethodsWe included a dataset of 4016 patients from a large RA cohort from 2012 to 2019. The tenderness and swelling of each joint were counted as a symptom, with 70 and 68 affected joints throughout the body, respectively. The relative contribution of various joints to the disease status assessment tools, VAS scores, and functional disability indexes was analyzed using multiple regression analysis.ResultsThe wrist showed the most significant contribution overall, especially in DASs and VASs, while the metacarpophalangeal and proximal interphalangeal joints made significant contributions to DASs and DAIs, but not to VASs and HAQs. The shoulder and the elbow significantly contributed to HAQs, but only the shoulder did to the VASs. The knee universally contributed to all of the tools, but the ankle played a minor but important role in most assessment tools, especially in HAQs. Similar but different contribution ratios were found between the sets of DASs, DAIs, VASs, or HAQs.ConclusionsEach joint makes a unique contribution to these assessment tools. The improvement or aggravation of symptoms in each joint affects the assessment tools in different manners.

Abstract Background Pulmonary artery involvement (PAI) in Takayasu arteritis (TAK) can lead to severe complications, but the relationship between the two has not been fully clarified. Methods We retrospectively investigated 166 consecutive patients with TAK who attended Kyoto University Hospital from 1997 to 2018. The demographic data, clinical symptoms and signs, comorbidities, treatments, and imaging findings were compared between patients with and without PAI. TAK was diagnosed based on the American College of Rheumatology Classification Criteria (1990) or the Japanese Clinical Diagnostic Criteria (2008). PAI was identified using enhanced computed tomography, magnetic resonance imaging, or lung scintigraphy. Results PAI was detected in 14.6% (n = 24) of total TAK patients. Dyspnea (25.0% vs. 8.6%; p = 0.043), pulmonary arterial hypertension (PAH) (16.7% vs. 0.0%; p < 0.001), ischemic heart disease (IHD) (29% vs. 9.3%; p = 0.018), respiratory infection (25.0% vs. 6.0%; p = 0.009), and nontuberculous mycobacteria (NTM) infection (20.8% vs. 0.8%; p < 0.001) were significantly more frequent, and renal artery stenosis (0% vs. 17%; p = 0.007) was significantly less frequent in TAK patients with PAI than in those without PAI. PAI and biologics were risk factors for NTM. Conclusions TAK patients with PAI more frequently have dyspnea, PAH, IHD, and respiratory infection, including NTM, than TAK patients without PAI.

Abstract Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.

Abstract Background The management of anxiety and depression symptoms in rheumatoid arthritis (RA) patients is vital. Previous study findings on this topic are conflicting, and the topic remains to be thoroughly investigated. This study aimed to clarify the association of RA disease activity with anxiety and depression symptoms after controlling for physical disability, pain, and medication. Methods We conducted a cross-sectional study of RA patients from the XXX Rheumatoid Arthritis Management Alliance cohort. We assessed patients using the Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and Hospital Anxiety and Depression Scale (HADS). Anxiety and depression symptoms were defined by a HADS score ≥ 8. We analyzed the data using multivariable logistic regression analyses. Results Of 517 participants, 17.6% had anxiety symptoms and 27.7% had depression symptoms. The multivariable logistic regression analysis demonstrated that DAS28 was not independently associated with anxiety symptoms (odds ratio [OR] [95% confidence interval; CI] 0.93 [0.48–1.78]; p = 0.82) and depression symptoms (OR [95% CI] 1.45 [0.81–2.61]; p = 0.22). However, DAS28 patient global assessment (PtGA) severity was associated with anxiety symptoms (OR [95% CI] 1.15 [1.02–1.29]; p = 0.03) and depression symptoms (OR [95% CI] 1.21 [1.09–1.35]; p

Objectives Numerous case reports have referred to new onset or flare of SLE after SARS-CoV-2 messenger RNA (mRNA) vaccines. Several observational studies showed that the short-term flare rate of SLE after SARS-CoV-2 vaccination is low. However, well-controlled clinical surveys are unavailable and the medium-term impact of the SARS-CoV-2 mRNA vaccines against the flare of SLE is uncertain. Therefore, we aimed to analyse the association between vaccination and medium-term subjective and objective disease activities of SLE and flares using matched pair methods.Methods Altogether, 150 patients with SLE from the Kyoto Lupus Cohort were included. Patients who received two doses of the SARS-CoV-2 mRNA vaccines were 1:1 matched with unvaccinated patients based on the first vaccination date. The outcome measures were the SLE Disease Activity Index-2000 (SLEDAI-2K), the Japanese version of the SLE Symptom Checklist Questionnaire (SSC-J) and the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index at 30, 60 and 90 days after vaccination.Results SLEDAI-2K levels were not significantly different in vaccinated and unvaccinated patients with SLE at 30, 60 and 90 days after the second vaccination (adjusted estimate (95% CI): 30 days: −0.46 (−1.48 to 0.56), p=0.39; 60 days: 0.38 (−0.64 to 1.40), p=0.47; 90 days: 0.40 (−0.54 to 1.34), p=0.41). Similar results were observed in the SSC-J score (adjusted estimate (95% CI), 30 days: 0.05 (−1.46 to 1.56), p=0.95; 60 days: −0.63 (−2.08 to 0.82), p=0.40; 90 days: 0.27 (−1.04 to 1.58), p=0.69) and flare index (adjusted OR (95% CI), 30 days: 0.81 (0.36 to 1.85), p=0.62; 60 days: 1.13 (0.50 to 2.54), p=0.77; 90 days: 0.85 (0.32 to 2.26), p=0.74).Conclusion SARS-CoV-2 vaccination did not significantly influence the medium-term subjective and objective disease activities or flares of SLE until 90 days after the second vaccination.

Abstract HLA-B*52 is an established genetic factor in Takayasu arteritis (TAK). Recently, single nucleotide polymorphisms (SNPs) in IL12B (rs6871626) and LILRA3 (rs103294) were newly identified as non-HLA susceptibility loci in TAK. Here, we examined how these SNPs contribute to clinical characteristics and vascular damage in TAK. We retrospectively reviewed the medical records of 99 TAK patients enrolled in our previous genome-wide association study, and whose genotypes for IL12B rs6871626, LILRA3 rs103294, and HLA-B*52 were available. Incidence of aortic regurgitation (AR) was significantly associated with the A allele (risk allele) of IL12B rs6871626 (CC 42%, AC 61%, AA 81%; p = 0.0052; odds ratio [OR] 2.45), as well as with the incidence of hypertension (p = 0.049; OR 1.82) and the proportion of patients who underwent aortic valve replacement (p = 0.023; OR 3.64). Regarding vascular damage, there was positive correlation between the Takayasu Arteritis Damage Score and the A allele of IL12B rs6871626 (CC 3.42 ± 2.71, AC 4.06 ± 3.25, AA 6.00 ± 2.81; p = 0.0035; β = 1.35) and between the Vasculitis Damage Index and the A allele (CC 3.47 ± 1.98, AC 4.33 ± 2.40, AA 5.37 ± 2.22; p = 0.0054; β = 0.96). Contrarily, no correlation was found between LILRA3 rs103294 and vascular damage. In the present study, IL12B rs6871626 was associated with vascular damage in TAK, whereas LILRA3 rs103294 was not. Genotyping of IL12B rs6871626 may help to identify patients at risk of disease progression.

The factors influencing long-term responses to a tumor necrosis factor inhibitor (TNFi) in rheumatoid arthritis (RA) patients currently remain unknown. Therefore, we herein conducted a multi-omics analysis of TNFi responses in a Japanese RA cohort. Blood samples were collected from 27 biological disease-modifying antirheumatic drug (DMARD)-naive RA patients at the initiation of and after three months of treatment with TNFi. Treatment responses were evaluated at one year. Differences in gene expression levels in peripheral blood mononuclear cells (PBMCs), plasma protein levels, drug concentrations, and the presence/absence of anti-drug antibodies were investigated, and a cell phenotypic analysis of PBMCs was performed using flow cytometry. After one year of treatment, thirteen patients achieved clinical remission (responders), while the others did not or switched to other biologics (non-responders). Differentially expressed genes related to treatment responses were enriched for the interferon (IFN) pathway. The expression of type I IFN signaling-related genes was higher in non-responders than in responders before and after treatment (P = 0.03, 0.005, respectively). The expression of type II IFN signaling-related genes did not significantly differ before treatment; however, it increased in non-responders and decreased in responders, with a significant difference being observed after three months of treatment (P = 1.2×10-3). The total number of lymphocytes and C-X-C Motif Chemokine Ligand 10 (CXCL10) protein levels were associated with the type I IFN signature (P = 6.7×10-7, 6.4×10-3, respectively). Hepatocyte growth factor (HGF) protein levels before treatment predicted fold increases in type II IFN (P = 0.03). These IFN signature-related indices (the number of lymphocytes, CXCL10, and HGF) significantly differed between responders and non-responders (P = 0.01, 0.01, and 0.04, respectively). A single-cell analysis revealed that the type I IFN signature was more highly enriched in monocytes than in other cell types. A deconvolution analysis of bulk-RNA sequence data identified CD4+ and CD8+ T cells as the main sources of the type II IFN signature in non-responders. Collectively, the present results demonstrated that the dynamics of the type I and II IFN pathways affected long-term responses to TNFi, providing information on its biological background and potential for clinical applications.

Abstract Background Excessive salt intake is thought to exacerbate both development of hypertension and autoimmune diseases in animal models, but the clinical impact of excessive salt in rheumatoid arthritis (RA) patients is still unknown. We performed a cross-sectional study to clarify the associations between salt load index (urinary sodium-to-potassium ratio (Na/K ratio)), current disease activity, and hypertension in an RA population. Methods Three hundred thirty-six participants from our cohort database (KURAMA) were enrolled. We used the spot urine Na/K ratio as a simplified index of salt loading and used the 28-Joint RA Disease Activity Score (DAS28-ESR) as an indicator of current RA disease activity. Using these indicators, we evaluated statistical associations between urinary Na/K ratio, DAS28-ESR, and prevalence of hypertension. Results Urinary Na/K ratio was positively associated with measured systolic and diastolic blood pressure and also with prevalence of hypertension even after covariate adjustment (OR 1.34, p

Abstract The efficacy and safety of immune checkpoint inhibitor (ICI) monotherapy in elderly patients with non‐small cell lung cancer (NSCLC) remain unclear, especially in patients older than 80 years. We retrospectively reviewed the records of 10 patients older than 80 years with NSCLCs treated by ICIs. The median age was 85 years (range, 82‐93 years), and 7 patients were men. The median length of follow‐up was 13 months (range, 4.5‐23 months). Eight patients had adenocarcinoma (3 of whom had exon 19 deletions), and two had squamous cell carcinoma. Expression of programmed cell death ligand 1 (PD‐L1) was ≥ 50% in 3 patients, between 1% and 49% in 4 patients, < 1% in 1 patient, and undetected in 2 patients. Patients with undetected PD‐L1 underwent transbronchial lung biopsy. Performance status was graded zero, one, and two in two, seven, and one patients, respectively. First‐, second‐, and third‐line treatments were administered to three, three, and four patients, respectively. The 2‐year overall survival rate was 30.0% (median, 285 days). Time to treatment failure rate on the 2 years was 10.0% (median, 167 days). One patient achieved a partial response, and one achieved a complete response. ICI‐associated adverse events occurred in five patients. In summary, ICIs were effective in some patients older than 80 years; however, some experienced adverse effects. Elderly patients must be selected carefully for ICI treatment.

Abstract Frailty is a geriatric syndrome characterized by anabolic-catabolic imbalance and multisystem dysregulation resulting in increased adverse health outcomes, and is closely related with dietary habits in the general population. Although chronic inflammatory diseases are thought to accelerate development of frailty, correlations between rheumatoid arthritis (RA), frailty and dietary habits have not been examined. We performed a cross-sectional study using our cohort database (KURAMA cohort), and classified 306 participants into three groups (robust, prefrail and frail) according to the Study of Osteoporotic Fracture (SOF) criteria. Multivariate logistic analysis revealed that the presence of frailty/prefrailty was significantly correlated with the disease activity score (DAS28-ESR) (OR 1.70 (1.30–2.22), p two times a week) was an independent covariate negatively correlated with frailty/prefrailty (OR 0.35 (0.19–0.63), p = 0.00060). In conclusion, habitual fish intake may play a key role in nutritional intervention to prevent progression of frailty and RA.

This article discusses the potential of avacopan, a medication that blocks a specific receptor, to improve the condition of patients with a type of blood vessel inflammation called ANCA-associated vasculitis. The article presents a case study of a patient who had high levels of a specific antibody despite treatment with other medications. However, when avacopan was added to their treatment, the antibody levels decreased. The authors suggest that avacopan may have the potential to lower antibody levels and improve the condition, but more research is needed. The article also provides information about conflicts of interest, funding, patient consent, and data availability. [Extracted from the article]

Abstract Background The positivity of anti-citrullinated protein/peptide antibodies (ACPAs) is a clinically useful diagnostic and prognostic marker in rheumatoid arthritis (RA). However, the significance of ACPA titer and its fluctuation remain unclear. This study aimed to assess the role of ACPA titer and its fluctuation on disease activity and the prognosis of RA. Methods Data obtained from the Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort was analyzed. Patients whose ACPA was measured at least twice between 2011 and 2019 and whose ACPA was positive at least once were included in this study. The association between the clinical variable and ACPA titer or its change was investigated. Results ACPA titer was measured in a total of 3286 patients, 1806 of whom were ACPA-positive at least once. Among them, the ACPA titer level was measured more than once in 1355 patients. Very weak correlation was observed between the ACPA titer level and disease activity. Additionally, there was no trend in the fluctuation of ACPA titer level in each patient; ACPA titer level fluctuated in some patients, but not in others. Patients with high variable levels of ACPA titer were more likely to relapse from remission. In the analysis of two consecutive ACPA measurements, the titer changes predicted the relapse from remission within a year of the second measurement. Conclusions The ACPA titer level fluctuated in some patients. Very weak correlation was observed between the ACPA titer level and disease activity. Fluctuation in ACPA titer level predicted relapse from remission in patients with RA.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a dermatomyositis (DM)-specific antibody, is strongly associated with interstitial lung disease (ILD). Patients with idiopathic inflammatory myopathy (IIM) who are anti-MDA5 antibody positive [anti-MDA5 (+)] often experience chest symptoms during the active disease phase. These symptoms are primarily explained by respiratory failure; nevertheless, cardiac involvement can also be symptomatic. Thus, the aim of this study was to investigate cardiac involvement in anti-MDA5 (+) DM. A total of 63 patients with IIM who underwent electrocardiography (ECG) and ultrasound cardiography (UCG) during the active disease phase from 2016 to 2021 [anti-MDA5 (+) group, n = 21; anti-MDA5-negative (-) group, n = 42] were enrolled in the study, and their clinical charts were retrospectively reviewed. The ECG and UCG findings were compared between the anti-MDA5 (+) and anti-MDA5 (-) groups. All anti-MDA5 (+) patients had DM with ILD. The anti-MDA5 (+) group showed more frequent skin ulcerations and lower levels of leukocytes, muscle enzymes, and electrolytes (Na, K, Cl, and Ca) than the anti-MDA5 (-) group. According to the ECG findings obtained during the active disease phase, the T wave amplitudes were significantly lower for the anti-MDA5 (+) group than for the anti-MDA5 (-) group (I, II, and V4–6 lead; p < 0.01; aVF and V3, p < 0.05). However, the lower amplitudes were restored during the remission phase. Except for the E wave, A wave and Sep e’, the UCG results showed no significant differences between the groups. Four patients with anti-MDA5 (+) DM had many leads with lower T wave and cardiac abnormalities (heart failure, diastolic dysfunction, myocarditis) on and after admission. Though anti-MDA5 (+) patients clinically improved after immunosuppressive therapy, some of their ECG findings did not fully recover in remission phase. In conclusion, anti-MDA5 (+) DM appears to show cardiac involvement (electrical activity and function) during the active phase. Further studies are necessary to clarify the actual cardiac condition and mechanism of these findings in patients with anti-MDA5 (+) DM.

Abstract Background Paracecal hernias, also known as pericecal hernias, are an exceptionally rare type of internal hernia. We report a unique case of paracecal hernia due to membranous adhesion of the omentum to the right paracolic gutter. Case presentation An 86-year-old female was admitted to our hospital with vomiting and abdominal pain. Laboratory findings showed a slightly elevated C-reactive protein level. Computed tomography scan showed dilated loops of the small intestine in the right paracolic gutter with medial displacement of the cecum and ascending colon. Internal hernia around the cecum due to postoperative adhesion after appendectomy was suspected, and she underwent emergency laparotomy. Intraoperative findings revealed the adhesion between the omentum and right paracolic gutter forming a cavity with the small intestine incarcerated. No abnormal adhesion in the ileocecal region was seen. We transected the omental adhesion from the orifice to the far end of the cavity near the hepatic flexure of the colon to release strangulation and to prevent recurrence. The patient was discharged on postoperative day 14 without complications. Conclusions Paracecal hernias have a type of membranous adhesion of the omentum to the right paracolic gutter. Surgeons should be aware of this paracecal hernia type, when they encounter the internal hernia.

ObjectivesThis study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.MethodsIFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.ResultsTwenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76–1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).ConclusionsThe quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

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

Objective Although mental disorder is one of the most common comorbidities of rheumatoid arthritis (RA) and is known as a critical influence on RA remission rates, there is little knowledge regarding a possible therapeutic strategy for depression or anxiety in a RA population. Most recently, clinical evidence of dietary improvement for depression has emerged in a general population, but the relationship between dietary habits and mental disorder has not been investigated in RA. The purpose of this study is to elucidate clinical associations between mental disorder (depression/anxiety), dietary habits and disease activity/physical function in patients with RA. Methods A cross-sectional study was performed with 267 female outpatients from the KURAMA database. Using the Hospital Anxiety and Depression Scale (HADS), we classified the participants into three groups by depression state, and their characteristics were compared. Using the 20-items on the self-reported food frequency questionnaire, we investigated the relationship between dietary habits and depression or anxiety, adopting a trend test and a multivariate standardized linear regression analysis for the HADS score of depression or that of anxiety as a dependent variable. Results According to the classified stage of depression, current disease activity (DAS28-CRP: 28-Joint RA Disease Activity Score-C-reactive protein) and the health assessment questionnaire disability Index (HAQ-DI) were significantly increased. Trend analyses revealed that the depression score was inversely associated with the consumption of three food (fish, vegetables and fruit) out of twenty as was the anxiety score with only fish intake. Furthermore, multiple linear regression analysis revealed that the depression score was negatively associated with frequent fish intake (≥ 3 times per week) (Estimate -0.53, p = 0.033), HAQ-DI score within normal range (Estimate -0.88, p ≤ 0.001) and MTX use (Estimate -0.60, p ≤ 0.023). For the anxiety score, multivariate analysis showed similar but not significant associations with variables except for HAQ-DI score. Conclusions In a RA population, both depression and anxiety had a significant and negative association with HAQ-DI score, and depression rather than anxiety had negative association with frequent fish intake. Modification of dietary habits such as increased fish consumption may have a beneficial effect on the depression state in RA patients.

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use.

OBJECTIVE:To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS:This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS:441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = -0.11, p

OBJECTIVE:To clarify the relationship among serum adiponectin, body composition, current disease activity and therapeutics of rheumatoid arthritis (RA). METHODS:We conducted a cross-sectional study in RA patients under treatment with agents including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors. A total of 351 subjects from the Kyoto University RA Management Alliance cohort (KURAMA) were enrolled in the analysis. We classified the participants into five body composition groups according to the cut-off points for obesity and visceral fat used in Japan: body mass index (BMI), 18.5 kg/m2 for underweight and 25.0 kg/m2 for obesity, and visceral fat area (VFA), 100 cm2 for visceral adiposity. RESULTS:Classification of body composition revealed that serum adiponectin levels and disease activity score (DAS28-ESR) in the low BMI group were significantly higher than those in the normal and overweight groups. Because both increased serum adiponectin and low BMI were previously reported as poor prognostic factors of RA, we performed multiple regression analysis to determine which factor was correlated with RA disease activity. Serum adiponectin level, but not BMI, was positively associated with DAS28-ESR (estimate = 0.0127, p = 0.0258). Subanalysis also showed that the use of bDMARD or JAK inhibitor did not have an obvious influence on circulating adiponectin. CONCLUSIONS:Classification of body composition and multiple regression analysis revealed a positive and independent correlation between serum adiponectin and DAS28-ESR in Japanese RA patients. Thus, serum adiponectin may be an important marker reflecting high disease activity of RA regardless of current medications.

Abstract Background Clinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs (bDMARDs) in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR)). It is unknown which bDMARD is advantageous for achieving BFR or under which conditions BFR can be considered. This study aimed to determine the factors associated with BFR achievement in clinical practice. Methods Patients with RA were enrolled from a Japanese multicenter observational registry. Patients with RA who achieved clinical remission (Disease Activity Score 28—C-reactive protein 6 months), Boolean remission, no glucocorticoid use at the time of bDMARD discontinuation, and use of TNFi(mAb) or CTLA4-Ig remained as independent factors associated with BFR. Conclusions BFR can be achieved in some patients with RA after bDMARD discontinuation in clinical practice. Use of TNFi(mAb) or CTLA4-Ig, sustained remission, Boolean remission, and no glucocorticoid use at the time of bDMARD discontinuation are advantageous for achieving BFR.

Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease, the specific feature of which is progressive joint destruction induced by synovitis. The universal consensus is that alleviation of the synovitis is essential to prevent joint destruction and achieve clinical remission. Main text We have shown that not only achieving but also maintaining remission is crucial to prevent the progression of joint destruction. Although regeneration of the damaged joints is considered very rare, accumulating evidence shows that it actually occurs in routine clinical practice as a result of strong inhibition of synovitis using highly potent medications. Oral and intravenous medications affect the whole body, but to promote joint regeneration in a particular joint, two potent options are intra-articular steroid injection and synovectomy. Conclusion In situations where strong inhibition of synovitis combined with self-regeneration cannot repair severe joint destruction, regenerative medicine may in the future play a crucial role in the regeneration of damaged joints.

Abstract Background A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of these cytokines in patients with TAK, stratifying them into those with or without the risk allele at the rs6871626 SNP. Methods Plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (HCs) by enzyme-linked immunosorbent assays. Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-γ+ or IL-17A+ cells to CD4+ T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells. Results The levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher in patients with TAK than in HCs, whereas there were no significant differences in the levels of plasma IL-23, supernatant IL-23, or supernatant IL-12p40. The levels of plasma IL-12p70, supernatant IL-12p40, and supernatant IL-12p70 were significantly higher in patients with the risk allele than in those without. The ratio of CD4+IFN-γ+ cells was significantly higher in patients with the risk allele, whereas CD4+IL-17A+ cells showed no differences. Conclusions The rs6871626 SNP in IL12B may influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines might play roles in the pathophysiology of TAK.