Factors associated with discrepancies in disease activity as assessed by SDAI and RAPID3 in patients with rheumatoid arthritis: Data from a multicenter observational study (T-FLAG).

OBJECTIVES: The present study aimed to examine discrepancies between assessments based on Routine Assessment of Patient Index Data 3 (RAPID3) and Simple Disease Activity Index (SDAI) in RA patients with controlled disease activity. METHODS: Data from 464 RA patients in SDAI remission or low disease activity (REM/LDA) were analyzed. Patient-reported outcome (PRO) measures, including Health Assessment Questionnaire Disability Index (HAQ-DI), 25-question Geriatric Locomotive Function Scale (GLFS-25), and Kihon checklist (KCL), were assessed. Logistic regression models were used to identify factors associated with RAPID3 moderate or high disease activity (MDA/HDA). Cutoff values of RAPID3 MDA/HDA for each PRO evaluation item were determined using receiver operating characteristic curve analysis. RESULTS: Among RA patients in SDAI REM/LDA, 84.9% were in RAPID3 REM/LDA. Multivariable analysis revealed that HAQ-DI, GLFS-25, and KCL were independently associated with RAPID3 MDA/HDA. Subdomain analysis of KCL revealed that activities of daily living, physical function, cognitive function, and depressive mood were significantly associated with RAPID3 MDA/HDA. Cutoff values for HAQ-DI and KCL were 0.38 and 8, respectively. CONCLUSIONS: In RA patients with controlled disease activity, discrepancies between RAPID3 and SDAI assessments were observed, with factors such as HAQ-DI, GLFS-25, and KCL being independently associated with RAPID3 MDA/HDA.

Comparison of effectiveness of methotrexate in patients with late-onset versus younger-onset rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J).

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.

Associations of frailty with RA-ILD and poor control of disease activity in patients with rheumatoid arthritis: A multi-center retrospective observational study.

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.

Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J).

OBJECTIVE: Various guidelines recommend that patients with early rheumatoid arthritis (RA) try to achieve clinical remission within 6 months, and early therapeutic intervention is important to this end. This study aimed to investigate short-term treatment outcomes of patients with early-diagnosed RA in clinical practice and to examine predictive factors for achieving remission. METHODS: Of the 210 patients enrolled in the multicenter RA inception cohort, 172 patients who were followed up to 6 months after treatment initiation (baseline) were included. Logistic regression analysis was used to examine the impact of baseline characteristics on achievement of Boolean remission at 6 months. RESULTS: Participants (mean age, 62 years) initiated treatment after a mean of 19 days from RA diagnosis. At baseline and 3 and 6 months after treatment initiation, proportions of patients using methotrexate (MTX) were 87.8%, 89.0%, and 88.3%, respectively, and rates of Boolean remission were 1.8%, 27.8%, and 34.5%, respectively. Multivariate analysis revealed that physician global assessment (PhGA) (Odds ratio (OR): 0.84, 95% confidence interval (CI): 0.71-0.99) and glucocorticoid use (OR: 0.26, 95% CI: 0.10-0.65) at baseline were independent factors that predicted Boolean remission at 6 months. CONCLUSION: After a diagnosis of RA, satisfactory therapeutic effects were achieved at 6 months after the initiation of treatment centered on MTX according to the treat to target strategy. PhGA and glucocorticoid use at treatment initiation are useful for predicting the achievement of treatment goals.

Factors associated with frailty in rheumatoid arthritis patients with decreased renal function.

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).

Disease activity at baseline is an independent predictor of frailty at one year in pre-frail patients with rheumatoid arthritis; a multicenter retrospective observational study.

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.

Relationship between locomotive syndrome and frailty in rheumatoid arthritis patients by locomotive syndrome stage.

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.

Does exercise therapy improve patient-reported outcomes in rheumatoid arthritis? A systematic review and meta-analysis for the update of the 2020 JCR guidelines for the management of rheumatoid arthritis.

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.

Systematic review and meta-analysis of biosimilar for the treatment of rheumatoid arthritis informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

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.

Patient satisfaction with total joint replacement surgery for rheumatoid arthritis: a questionnaire survey for the 2020 update of the Japan college of rheumatology clinical practice guidelines.

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.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

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.

Patients' perspectives of rheumatoid arthritis treatment: a questionnaire survey for the 2020 update of the Japan college of rheumatology clinical practice guidelines.

OBJECTIVES: This study aimed to evaluate patients' opinions regarding their rheumatoid arthritis (RA) therapy and to reflect the patients' perspectives in the 2020 update of the Japan College of Rheumatology clinical practice guidelines. METHODS: A self-administered questionnaire was mailed to 1600 members of the Japan Rheumatology Friendship Association, who were randomly selected by age and prefecture. RESULTS: A total of 1156 patients returned the questionnaire (response rate, 72.3%; mean age, 63.0 ± 11.9 years). Those who reported having discussed their treatment goals with their doctors (450 respondents, 38.9%) were more likely to be satisfied with their current medical care (odds ratio, 7.13; 95% CI 4.72-10.8) compared with those who had not discussed their goals nor had them explained (287 respondents, 24.8%). The benefits exceeded the adverse effects for all pharmacotherapy (methotrexate, corticosteroids, conventional synthetic antirheumatic drugs, biological agents, Janus kinase inhibitor, and anti-RANKL antibodies). However, while 74.2% of the respondents using biological agents perceived that 'the favorable aspects outweighed the unfavorable aspects,' most of those taking anti-RANKL antibodies (69.2%) felt uncertain. CONCLUSIONS: The questionnaire successfully collected information regarding patients' perceptions regarding their therapy. Further implementation of treat-to-target is necessary in Japan to improve patient satisfaction.

Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

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.

Impact of social support on severity of depressive symptoms by remission status in patients with rheumatoid arthritis.

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.

Relationship between disease activity of rheumatoid arthritis and development of locomotive syndrome: A five-year longitudinal cohort study.

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.

Depression, physical function, and disease activity associated with frailty in patients with rheumatoid arthritis.

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.

Higher doses of methotrexate associated with discontinuation of oral glucocorticoids after initiation of biological DMARDs: A retrospective observational study based on data from a Japanese multicenter registry study.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Improvement in matrix metalloproteinase-3 independently predicts low disease activity at 52 weeks in bio-switch rheumatoid arthritis patients treated with abatacept.

OBJECTIVES: To explore predictive factors including MMP-3 for achievement of low disease activity (LDA) at 52 weeks in bio-switch rheumatoid arthritis (RA) patients treated with abatacept, for whom obtaining a good clinical response can be difficult. METHODS: Participants were 423 consecutive patients with RA treated with abatacept who were observed for longer than 52 weeks and registered in the TBCR, a Japanese multicentre registry system. Multivariate logistic regression analysis was used to study factors that predict the achievement of LDA at 52 weeks in bio-naïve (n=234) and bio-switch (n=189) groups. RESULTS: ROC analysis revealed that MMP-3 improvement rates at 12 weeks in bio-switch patients had the highest AUC with a cut-off value of 20.0% for predicting LDA achievement at 52 weeks. Multivariate logistic regression analysis revealed that, in addition to DAS28-CRP at baseline, achieving 20% improvement in MMP-3 levels at 12 weeks was an independent predictive factor (adjusted OR: 4.277, p=0.003) in the bio-switch group, whereas DAS28 was the only predictor in the bio-naïve group. Patients who achieved 20% improvement in MMP-3 levels at 12 weeks had significantly higher achievement rates of LDA at 52 weeks compared to those who did not achieve 20% improvement in the bio-switch group (60.0 vs. 33.3%, p=0.001). CONCLUSIONS: Our findings suggest that improvement in MMP-3 levels is key to predicting the clinical efficacy of abatacept. Closer attention paid not only to major clinical indices, but also changes in MMP-3 levels, could improve our ability to optimise clinical results when treating bio-switch patients.

Characteristics of patients with rheumatoid arthritis undergoing primary total joint replacement: A 14-year trend analysis (2004-2017).

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.

Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab: An interventional study.

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.