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Objectives To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). Methods We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. Results After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25–2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. Conclusion Patients with those factors should be dealt with appropriate cautions to strike a risk–benefit balance of orthopedic surgeries.

Objective This study aimed to evaluate satisfaction with total joint replacement (TJR) surgery among patients with rheumatoid arthritis (RA). Methods We mailed questionnaires to randomly selected members of the Japan Rheumatism Friendship Association, stratified by age and prefecture, throughout Japan. The questionnaire collected demographic and clinical characteristics as well as patients’ satisfaction with TJR and their current therapy. Results Of the 1156 patients who returned the questionnaire, 339 (29.3%) responded that they had had TJR of any type. The mean age was 66.6 years, and 94.4% were women. The mean time period from the hip and knee TJR was 14–15 years. Over half of the patients who had had TJR were satisfied with the results, especially those who had had hip (89.6%) and knee TJR (87.3%), who reported a high level of satisfaction. Multivariable linear regression analysis revealed that, in patients with knee TJR, satisfaction with current therapy was significantly related to whether they were satisfied with the results of the surgery. Conclusion Most patients with RA who had undergone TJR were satisfied with the results even after a long period of time, and their level of satisfaction was associated with their satisfaction with current therapy.

Glucocorticoids are important drugs used to treat rheumatoid arthritis. We recommend glucocorticoid discontinuation as soon as possible given the associated side-effects, but many patients continue to take oral glucocorticoids long-term. The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating biological disease-modifying antirheumatic drugs (bDMARDs). Subjects were 564 patients from a Japanese multicenter registry who were administered glucocorticoids and methotrexate (MTX) followed by initiation of the first bDMARD. We examined the status of oral glucocorticoid use at 52 weeks after initiating the first bDMARD. By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariable analysis identified age, MTX dose, and glucocorticoid dose as factors independently associated with glucocorticoid discontinuation. After adjusting for baseline characteristics using propensity score matching, among patient groups administered MTX ≤ 8 mg/week and MTX > 8 mg/week, 105 pairs remained. A significantly higher rate of glucocorticoid discontinuation (41.0%) was noted for patients administered MTX > 8 mg/week. Our findings suggest that glucocorticoids may be discontinued after initiating bDMARDs. Moreover, higher MTX doses (>8 mg/week) at the time of bDMARD initiation were associated with glucocorticoid discontinuation among patients treated with bDMARDs.

Objectives This study aimed to evaluate the impact of exercise therapy on patient-reported outcomes (PROs) in rheumatoid arthritis (RA) as part of the process of updating the 2020 Japanese guidelines for the management of RA according to the Grading of Recommendations, Assessment, Development, and Evaluation system. Methods We searched PubMed, Japana Centra Revuo Medicina Web, and the Cochrane Library (from 2009 to 2018) to identify articles that evaluated PROs of exercise therapy and RA disease activity. Results A total of 662 articles were identified, including nine RCTs, and meta-analyses were performed on six RCTs on systemic exercise therapy and three RCTs on upper extremity exercise therapy. Analyzed exercise therapies were diverse, differing in target population, intervention method, and duration. Significant improvements were observed in the Health Assessment Questionnaire Disability Index (mean difference −0.35, 95% confidence interval (CI): −0.60 to −0.10), pain (standardized mean difference −2.04, 95% CI: −3.77 to −0.32), and SF-36. For upper extremity exercise therapy, significant improvements in PROs (Disabilities of the Arm, Shoulder, and Hand Questionnaire, Michigan Hand Outcome Questionnaire) were observed. Conclusion Exercise therapy in RA treatment improves patient subjective assessment of pain, physical function, and quality of life.

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.

This study aimed to determine the influence of gastrointestinal (GI) symptoms on patient global assessment (PGA) in patients with rheumatoid arthritis (RA). This cross-sectional study examined 837 patients with RA treated in our department between April 1 and September 30, 2017. GI symptoms were evaluated by the Gastrointestinal Symptom Rating Scale, wherein a score of ≥ 2 was considered “symptomatic.” PGA and proportion of PGA ≤ 1 were compared between symptomatic and asymptomatic patients. Factors associated with achievement of PGA ≤ 1 were assessed with logistic regression models. Of our study population, 28%, 24%, 28%, 28%, and 45% had reflux, abdominal pain, indigestion, diarrhea, and constipation, respectively, and 64% had at least one GI symptom. The symptomatic group had a significantly higher PGA score than the asymptomatic group in all GI symptoms (P

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).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.Subjects were divided into the LS group (Tight control of RA disease activity for deeper remission may be needed to prevent the development of LS.

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 u...

Discontinuation of biologic therapy in rheumatoid arthritis is attributable to various reasons, with the most important cause being insufficient response. In this study, we investigated the association between rheumatoid factor (RF) and anti-citrullinated protein autoantibody (ACPA) status and the discontinuation of tumor necrosis factor inhibitors (TNFi) therapy due to insufficient response in bio-naïve rheumatoid arthritis (RA) patients.This study included patients enrolled in the Tsurumai Biologic Communication Registry in Japan. The crude comparison of TNFi discontinuation due to ineffectiveness between seropositive and seronegative patients was analyzed using the cumulative incidence function of competing events and Gray test. We assessed the associations between baseline patient characteristics and discontinuation of TNFi therapy due to insufficient response using Fine-Gray proportional hazard regression. Fine-Gray proportional hazard analysis considered competing events of interest, including insufficient response, adverse event, palliation, and personal reasons.Of 1237 patients evaluated, 79.3% were positive for RF and 85.4% for ACPA; 72.6% were double positive and 11.1% were double negative. TNFi therapy had been discontinued because of insufficient response at 200 weeks in 19.8% RF-positive, 16.7% RF-negative, 23.0% ACPA-positive, and 13.8% ACPA-negative patients. There was a significantly higher discontinuation rate due to insufficient response in ACPA-positive patients than in ACPA-negative patients using Gray test, with a similar trend as that for RF status. RF positivity was significantly predictive of the discontinuation of TNFi therapy due to ineffectiveness using Fine-Gray proportional hazard regression analysis after adjusting for baseline characteristics, including age, sex, stage, class, disease activity at baseline, methotrexate use, and prednisolone use [hazard ratio 1.73 (95% confidence interval 1.07-2.80)].Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients. Key Points • RF positivity is related to a higher discontinuation rate of TNFi therapy due to ineffectiveness. • ACPA is not predictive of a discontinuation of TNFi therapy due to ineffectiveness.

To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(−)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(−)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (− 1.35/− 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks. In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in ‘real-world’ settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.

Objectives To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. Methods PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. Results Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of −2.79 (95% confidence interval [CI] − 3.74 to −1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90–4.21) and 1.32 (95%CI 0.53–3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64–0.91) and 1.92 (95%CI 1.31–2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. Conclusion This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.

Objectives To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA. Methods PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98–1.10) and 0.84 (0.61–1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69–1.26) and 2.15 (0.55–8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76–1.12) and 1.41 (0.32–6.15) in those who continued the reference bDMARDs. Conclusion Biosimilars and reference bDMARDs were equally useful for the management of RA.

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.

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.

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.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).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.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.

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.

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combinati...

Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice.Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment.Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model).Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX.

Objective This study aimed to assess the association between chest computed tomography (CT) findings and incidence of respiratory adverse events (RAEs), and to detect risk factors for RAEs, in RA patients treated with long-term biological therapy. Methods Clinical and radiological data of 332 RA patients who were treated with biological disease-modifying antirheumatic drugs were collected. CT data were assessed by an experienced radiologist. Patients were categorized into the interstitial lung disease (ILD) group (n = 29), airway disease (AD) group (n = 76), co-existing ILD and AD (Co-existing) group (n = 6), and the group without detectable change (WDC, n = 221) based on CT findings and scores. The incidence of RAEs was calculated for each group, and risk factors for RAEs from CT findings were explored. Results We identified 41 RAEs, including acute onset or exacerbation of ILD (ILD events, n = 15), respiratory tract infection events (infection events, n = 21), and other events (n = 6). Cumulative incidences of ILD events were 20.2, 3.75, 47.2, and 1.94 (/1000 patient-years: PY) in the ILD, AD, Co-existing, and WDC groups, respectively, and those of infection events were 11.3, 17.6, 23.6, and 2.39 (/1000PY), respectively. Severity, as assessed by CT scores, was correlated with the incidence of RAEs. Risk factors for ILD events were reticular and honeycomb changes, and those for infection events were consolidation, bronchial wall thickening, bronchiectasis, bronchiolitis, air trapping, and atelectasis after adjusting for background factors. Conclusion Our findings highlight particular CT findings that are associated with RAEs in RA patients undergoing long-term biological therapy.

Background Of the treatment of rheumatoid arthritis (RA), biologic agent therapies are chosen, if disease activity remains moderate or high despite csDMARDs therapy. In the elderly, with comorbidity and their less spare ability, safety is often concerned in the choice of biologic agent. Objectives We investigated the tendency to choose biologic agent and drug continuation rates in elderly in last decade. Methods Records of relevant patients with RA were collected from the Tsurumai Biologic Communication Registry, wherein the department of Nagoya University and 20 affiliated hospitals in Japan are enrolled. A total of 873 biologics-naive and age 65 and older patients were recruited from January 2004 to December 2014. We studied the choice of the biologic agent year by, and baseline disease activity and concomitant methotrexate (MTX) among TNF inhibiters, tocilizumab (TCZ), and abatacept (ABT) groups. Drug continuation rates were compared among TNF inhibiters, TCZ, and ABT groups. Results From 2005 to 2010, etanercept (ETN) was used the most (2007; 73.5%, 2009; 65.9%). After the advent of ABT, ABT was used the most (2011; 44.3%, 2014; 38.8%). Baseline disease activity slightly decreased as a whole (DAS28-CRP; 4.88 to 4.44). Despite baseline disease activity of TNF inhibitors group decreased (DAS28-CRP; 4.88 to 4.37), that of TCZ group increased (DAS28-CRP; 4.94 to 6.24). In 2011–2014, baseline disease activity of TCZ group (5.85) was higher than that of TNF inhibiters group (5.11) (p Conclusions ETN was used most before the advent of ABT. After the advent of ABT, ABT was used most and ETN decreased. This selection was made for speculation that ABT is lower risk than other biological agents. Baseline disease activity slightly decreased showing that tight control management became also popular among elderly. In 2011–2014, concomitant MTX rate and dose were lower in ABT group, but 2 years drug continuation rate was the highest. Disclosure of Interest None declared