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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.

To validate and establish targets for the physician-based clinical scale for foot surgery in rheumatoid arthritis (RA) patients based on patient-reported outcomes from a multicenter prospective cohort.We collected data on demographics, values from the RA foot and ankle scale by the Japanese Society for Surgery of the Foot (JSSF-RA), and patient-reported outcomes (PROs) including the Health Assessment Questionnaire Disability Index (HAQ-DI) before (baseline) and 6 and 12 months after joint surgery. Target values for JSSF-RA were determined according to the lower limit of the 95% CI of JSSF-RA in patients with HAQ-DI ≤0.5 after adjusting for age and sex. We used multiple linear regression analysis to examine potential predictors of JSSF-RA target achievement at baseline.Cross-sectional analysis was conducted on data from 417 cases. The JSSF-RA target for foot and ankle surgery was set at 74 according to the JSSF-RA value corresponding to HAQ-DI ≤0.5 (mean 77.6, 95% CI: 74.3-80.9). Longitudinal analysis of patients who underwent foot surgery (A JSSF-RA value of 74 represents an important target for patients with RA who have undergone foot surgery. In order to achieve this target, the timing of the surgery should be considered in the treatment of established RA patients.

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.

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.

Rheumatoid arthritis is a chronic inflammatory disease characterized by inflammation of the synovial membrane of the joints. The destruction of the joints results in a narrowing of the interarticular space, distortion of the joints, and deformity of the fingers. Currently, the mainstream method of diagnosing such symptoms is by direct visual inspection of X-ray images by a physician. However, the diagnosis of the progression of joint destruction requires a lot of time and effort because the number of joints to be observed is large and it is difficult to accurately read minor pathological changes. In addition, the subjective evaluation by the physician is subject to large intra- and inter-examiner variability and lacks reproducibility, which is a major problem. As a means to solve these problems, the goal of this paper has been to develop a diagnosis support system by image processing that is quantitative and labor-saving. In this paper, we propose a method to improve the accuracy of joint position estimation in X-ray images in order to obtain the temporal variation between two images, and confirm the effectiveness of our proposed method by experiments.

Early detection of rheumatoid arthritis makes remission possible. In this study, we aimed to implement the automatic early detection of rheumatoid arthritis. Experimentally, we focused on third finger joint detection, and highly accurate results were obtained.

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.

Rheumatoid arthritis is one of the diseases to narrow Joint Space Distance (JSD), while it is getting worth. The JSD has not been established to measure the JSD exactly, it is difficult to find the disease at the early stage. So, an application to measure the JSD has been developed, and it is possible to measure the JSD exactly. However, in this application, doctors have to process manually at a few points. Therefore, we propose an automatic measurement method for the rheumatoid application. The experimental results show that it is possible to measure joints automatically in X-ray images, which are taken clearly. Therefore, our proposed measurement algorithm is effective for rheumatoid arthritis medical examinations.

This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis.DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

Background Loss of physical function is a clinical feature of RA. Total management including reconstructive joint surgery and rehabilitation should be needed for further improvements of physical function for established RA patients. In these days, it is very important to evaluate the effectiveness of joint surgery as well as drug therapy based on patient-reported outcome (PRO). Objectives The purpose of this study is to explore the relationship among depression, clinical variables and other PROs including physical function and improving of depressive status with joint surgery. Methods Multicenter prospective observational cohort study was conducted among patients who underwent elective joint surgery for RA from April 2012 to March 2016 (Study registration: UMIN000012649) (ref.1). In this study, we collected data at baseline and at 6 or 12 months after the surgery. These data were as follow; age, sex, disease duration, drug therapies, and disease activity (DAS28-CRP), and PRO measures [HAQ-DI, EQ-5D (QOL), pain VAS and BDI-II (depression)]. Correlation between BDI-II and other variables were determined using multiple liner regression analysis with forward stepwise. Results Totally, 346 patients before elective joint surgery were analyzed cross-sectionally. Mean age, disease duration, pain(VAS), DAS28, HAQ-DI, EQ-5D and BDI-II were 64.2 years, 17.0 years, 36.2 mm, 3.02, 1.111, 0.641 and 13.0, respectively. 52.6% of elective joint surgeries were in upper limbs and 47.4% were in lower limbs. Multiple liner regression analysis showed that HAQ-DI [β:-0.48, p Conclusion Loss of physical function is an important factor for impairment of depressive status as well as QOL in established RA patients. Improving of physical function with joint surgery in lower limbs caused improving of depressive status. Rheumatologists should take the joint surgery into consideration as effective intervention for treatment of established RA patients. References [1] Kojima T, et al. Int J Rheum Dis. 2018. doi: 10.1111/1756-185X.13394. Acknowledgement The registry used in this study was supported by a grant from the Ministry of Health, Labour and Welfare (H2424YN002-00) to Naoki Ishiguro Disclosure of Interests Toshihisa Kojima Grant/research support from: Chugai Pharmaceutical (Investigator Initiated Study), Novartis, Nippon Kayaku, Eli Lilly, Eisai, Speakers bureau: Chugai Pharmaceutical, Takeda Pharmaceutical, Pfizer, Eli Lilly Japan, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Astelas, UCB, Janssen Pharmaceutical, Tanabe Mitsubishi, Masayo Kojima: None declared, Hajime Ishikawa: None declared, Sakae Tanaka Grant/research support from: KYOCERA Corporation and Asahi Kasei Corporation, Consultant for: Amgen Astellas BioPharma K.K., KYOCERA Corporation, Pfizer and Daiichi Sankyo Co., Ltd., Speakers bureau: Asahi Kasei Corporation, Astellas Pharma Inc, Ayumi Pharmaceutical Corporation, Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd., Mitsubishi Tanabe pharma Corporation, Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Eli Lilly, Hisamitsu Pharmaceutical Co, Inc., Pfizer, Bristol-Myers., Keiichiro Nishida: None declared, Nobuhiko Haga: None declared, Yukio Masaoka: None declared, Jun Hashimoto: None declared, Hisaaki Miyahara: None declared, Yasuo Niki: None declared, Tomoatsu Kimura: None declared, Hiromi Oda: None declared, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Koji Funahashi: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant for: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama

Objective.To evaluate the rates of retention and discontinuation of adalimumab (ADA) due to efficacy and safety in Japanese patients with rheumatoid arthritis (RA).Methods.All patients with RA (n = 476) who were treated with ADA in the Tsurumai Biologics Communication Registry were enrolled.Results.The retention rate of ADA was 46% at 5 years. When focusing on insufficient efficacy, previous biologics use and high baseline disease activity were significant risk factors for up to 1 year. Methotrexate (MTX) use was a significantly low risk factor after 1 year of treatment.Conclusion.Concomitant MTX contributes to the longterm efficacy of ADA therapy.

This study aimed to identify predictive factors for achieving low disease activity (LDA) in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT). Patients who were registered in the multicenter observational Tsurumai Biologics Communication Registry (TBCR) were enrolled in this study. Predictive factors for LDA achievement at each time point were determined by univariate and multivariate logistic regression analyses. The cutoffs of 28-point count Disease Activity Score (DAS28)-C-reactive protein (CRP) and ΔDAS28-CRP from baseline up to 24 weeks for LDA achievement at 52 weeks were explored using receiver operating characteristic (ROC) curves. Of 2771 RA patients registered until 2013, 76 with moderate or high disease activity were selected. Twenty-six percent of the patients achieved LDA. Multivariate analysis confirmed that DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks were independent factors for LDA achievement at 52 weeks [odds ratio (OR) 0.26, 95% confident interval (CI) (0.12-0.56), OR 0.25, 95% CI (0.11-0.57), respectively]. The best cutoff values of DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks for LDA at 52 weeks were 3.9 (sensitivity 0.85, specificity 0.78) and -0.97 (sensitivity 0.70, specificity 0.70), respectively. Seventy-one percent of patients who achieved both of these cutoff values at 12 weeks achieved LDA at 52 weeks. Our findings suggest that the clinical course up to 12 weeks is important for predicting long-term outcomes when switching from TNFis to ABT.

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.

Background Total management including reconstructive joint surgery and rehabilitation should be needed for further improvements of physical function for long-standing RA patients. It is very important to set treatment goal for those management. Objectives The purpose of this study is to set treatment target using Timed Up and Go test (TUG) in relation to achievement of HAQ-DI remission (HAQ-DI Methods Multicenter prospective observational cohort study was conducted among patients who underwent elective joint surgery for RA from April 2012 to March 2016 (Study registration: UMIN000012649). In this study, we collected data including age, sex, disease duration, drug therapies, and disease activity (DAS), TUG, and patient-reported outcome [HAQ-DI, EQ-5D (QOL), patient’s global assessment (PtGA) and BDI-II (depression)] at baseline and at 6 or 12 months after the surgery. Association between TUG and achievement of HAQ remission and cut-off values for HAQ remission were also determined using logistic regression analysis with adjustment of age and sex and ROC curve, respectively. Results Totally, 139 patients with elective joint surgery in lower limbs were analysed. Mean age, disease duration, HAQ-DI and TUG were 65.4 years, 17.5 years, 1.022, and 12.7 s, respectively. Performed joint surgeries were total hip arthroplasty; 10.1%, total knee arthroplasty; 33.8%, total ankle arthroplasty or ankle fixation; 10.1%, and forefoot arthroplasty; 46.0%. The surgeries can significantly improve the outcome measures, including TUG, DAS, PtGA, pain, EQ-5D and BDI-II other than HAQ-DI. In this study, 45 of 139 patients (32.4%) had HAQ remission status at baseline. 18 of 94 patients (19.1%) who had HAQ-DI >0.5 can achieve HAQ remission with the surgery. Notably, TUG at last observation was significantly associated with achievement of HAQ remission even after adjustment for age, sex, and DAS (1 s increasing of TUG. OR:0.72, 95% CI: 0.53–0.97). The adjusted-TUG at last observation of patients with achievement of HAQ remission was 9.2 s (95% CI: 5.6–12.8) (figure 1). Cut-off of TUG at observation for achievement of HAQ remission was 9.2 s based on ROC analysis (figure 2). Importantly, We confirmed significant more improving of EQ-5D, HAQ-DI and TUG in patients who achieved TUG 9.2 s at last observation than in patients who did not (figure 3). Conclusions TUG was significantly associated with PRO; HAQ-DI and EQ-5D. The cut-off values of TUG (9.2 s) should be important to achieve good QOL and physical function for patients with joint surgery in lower limbs and could be suitable target for surgical procedure. Acknowledgements This study is supported by grant from the Japanese Ministry of Health, Labour and Welfare Disclosure of Interest None declared

Objective This prospective observational cohort study aimed to set targets for lower limb joint surgery based on the Timed Up and Go test (TUG), an objective functional outcome measure, in patients with established rheumatoid arthritis (RA). Methods We validated TUG as an outcome measure of lower limb joint surgery and compared it with changes in patient-reported outcomes, including the Health Assessment Questionnaire Disability Index (HAQ-DI) and European Quality of life scale with five dimensions (EQ-5D). Changes in these outcomes were compared by performed surgery and by achievement of the minimal clinically important difference (MCID) for EQ-5D using univariate analysis of variance. Associations between TUG and HAQ remission (HAQ-DI ≤0.5) were determined using logistic regression analysis. Cut-off values of TUG at baseline and 6 months after surgery for HAQ remission were determined using receiver operating characteristic curves. Results A total of 126 patients were analyzed. Mean age, HAQ-DI, and TUG were 65.4 years, 1.036, and 12.8 seconds, respectively. After surgery, patients showed improvements in TUG as well as HAQ-DI. TUG at 6 months after surgery was significantly associated with HAQ remission (adjusted OR: 0.78; 95% CI: 0.65-0.93). TUG cut-off values at baseline and 6 months after surgery for achieving HAQ remission were 12.1 and 8.8 seconds, respectively. Significant improvements in TUG (∆TUG, 3.7 seconds) were associated with achievement of the MCID for EQ-5D (≥0.05) at 6 months after surgery. Conclusion Timed Up and Go test is a useful tool for assessing the outcome of lower limb joint surgery in RA patients. We propose that TUG ≤9 seconds could be an objective target for achieving good physical function after lower limb joint surgery.

Aim This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. Methods We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. Results A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). Conclusion TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.

Objective To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. Methods A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias. Results Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6–8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20–0.65). Additionally, propensity score–matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032). Conclusion Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.

This retrospective observational study aimed to examine the efficacy of iguratimod with and without concomitant methotrexate (MTX) and to estimate the adequate observational period for predicting low disease activity (LDA) achievement at 24 weeks in patients with rheumatoid arthritis (RA).All patients treated with iguratimod were registered in a Japanese multicenter registry. Multivariate analyses were performed to identify predictive factors for LDA achievement at 24 weeks. Receiver operating characteristic (ROC) curve analyses were performed to estimate the association of 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) at each time point with achievement of LDA at 24 weeks and determine a cut-off for DAS28-ESR.A total of 123 patients were treated with iguratimod with (n = 65) or without (n = 58) MTX. Iguratimod therapy resulted in significant clinical improvement in both groups. Multivariate analysis revealed that DAS28-ESR at each time point was an independent significant predictor of LDA achievement at 24 weeks. Cut-off values of DAS28-ESR at 12 weeks based on ROC curves were 3.2 and 3.6 in patients with and without MTX, respectively.Iguratimod was effective in RA patients in clinical practice. Our results suggest that 12 weeks may be a sufficient period to judge the medium-term efficacy of iguratimod in patients treated with and without MTX.

This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.

Objective.Our study aimed to evaluate the longterm efficacy and safety of abatacept (ABA), and to explore factors that increase its longterm efficacy in patients with rheumatoid arthritis (RA) treated in routine clinical practice.Methods.There were 231 participants with RA treated with ABA who were prospectively registered in a Japanese multicenter registry. They were followed up for at least 52 weeks.Results.Mean age of the patients was 64.3 years, mean disease duration was 12.1 years, mean 28-joint Disease Activity Score (DAS28)-C-reactive protein was 4.49, and 48.5% of patients were concomitantly treated with methotrexate (MTX). Overall retention rate of ABA was 77.1% at 52 weeks; 14.8% of patients discontinued because of inadequate response and 3.5% because of adverse events. The proportion of patients achieving DAS28-defined low disease activity (LDA) significantly increased from baseline to 52 weeks (7.3% to 43.8%, p < 0.01); 40.9% of patients who did not achieve LDA at 24 weeks had more than 1 categorical improvement in DAS28-defined disease activity at 52 weeks. Multivariate logistic regression revealed concomitant MTX use to be an independent predictor of the categorical improvement in DAS28-defined disease activity from 24 to 52 weeks (adjusted OR 3.124, p = 0.010).Conclusion.In routine clinical practice, ABA demonstrated satisfactory clinical efficacy and safety in patients with established RA for 52 weeks. The clinical efficacy of ABA increased with time even after 24 weeks, and this was strongly influenced by concomitant MTX use. Our study provides valuable real-world findings on the longterm management of RA with ABA.

In medical imaging, X-ray photographic images are commonly used, but these have low resolution and a significant amount of noise because radiation levels are minimized for patient safety. In this paper, we propose a novel measurement algorithm for X-ray images generated by our proposed super-resolution method. To validate the measurement accuracy of our proposed algorithm, we construct a model for the measurement algorithm for joint space distance using a 3D printer, and obtain X-ray images of it. Experimental results show that the distances are measured with high accuracy.

Objective: To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. Methods: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. Results: A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. Conclusions: Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability., Published online: 25 Jul 2017

Objective: This study aimed to investigate predictors of biologic discontinuation due to insufficient response as a surrogate for relapse in patients with rheumatoid arthritis (RA) who achieved clinical remission with biologic treatment. Methods: This study was performed based on data from a multicenter registry, and included 404 patients who achieved clinical remission within the first year of treatment with their first biologic. Cumulative retention rate of the first biologic was estimated using Kaplan–Meier curves, and the impact of patient characteristics on biologic discontinuation was assessed with Cox proportional hazards models. Results: During follow-up, 50 patients discontinued their first biologic due to insufficient response. Overall discontinuation rates due to insufficient response after achieving remission were 6%, 11%, and 19% at 1, 2, and 5 years, respectively. Multivariate analysis revealed that concomitant glucocorticoids at achieving remission [hazard ratio (HR): 3.80, 95% confidence interval (CI): 1.89–7.64)] and a higher level of C-reactive protein (CRP) at achieving remission (HR: 1.47 per 1 mg/dL, 95% CI: 1.09–1.99) independently predict discontinuation due to insufficient response after achieving remission. Conclusion: Patients with RA who achieved remission with concomitant glucocorticoid treatment and a higher level of CRP are at high risk of subsequent biologic discontinuation due to insufficient response., Published online: 13 Jul 2017

Super-resolution techniques have been widely used in fields such as television, aerospace imaging, and medical imaging. In medical imaging, X-rays commonly have low resolution and a significant amount of noise, because radiation levels are minimized to maintain patient safety. So, we proposed a novel super-resolution method for X-ray images, and a novel measurement algorithm for treatment of rheumatoid arthritis (RA) using X-ray images generated by our proposed super-resolution method. In this paper, we improve measurement accuracy for our proposed method. Moreover, to validate it for our proposed algorithm, we make a model for measurement algorithm about joint space distance using a 3D printer, and X-ray images are obtained to photograph it. Experimental results show that high quality super-resolution images are obtained, and the measurement distances are measured with high accuracy. Therefore, our proposed measurement algorithm is effective for RA medical examinations.

OBJECTIVE Only a few studies have assessed predictive factors for the long-term efficacy of abatacept. This study aimed to provide clinical evidence of an adequate observational period for predicting low disease activity (LDA) achievement at 52 weeks in RA patients treated with abatacept. METHODS Participants were all patients registered in a Japanese multicentre registry who were treated with abatacept and had at least 52 weeks of follow-up (n = 254). RESULTS Areas under the receiver operating characteristic curves for the 28-joint count with CRP (DAS28-CRP) at each time point for LDA achievement at 52 weeks were: 0.686 (cut-off score: 4.6) at baseline, 0.780 (3.8) at 4 weeks, 0.875 (3.3) at 12 weeks, and 0.900 (3.0) at 24 weeks. Although patients with a DAS28-CRP score < 3.0 at 24 weeks had the highest proportion of LDA achievement at 52 weeks (79.3%), the proportion for those with a score < 3.3 at 12 weeks was comparable (77.2%, P = 0.697). Proportions were significantly lower in patients with a score < 3.8 at 4 weeks or < 4.6 at baseline. Multivariate logistic regression demonstrated that a DAS28 score of < 3.3 at 12 weeks was an independent strong predictor for LDA at 52 weeks (adjusted odds ratio: 15.2, P < 0.001). CONCLUSION Twelve weeks is an adequate observational period to judge the long-term clinical efficacy of abatacept, and is about as early as the period for assessing TNF blockade therapy.

The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX.A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents.Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model.Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.

The purpose of this study was to identify the effects of concomitant use of MTX and baseline characteristics for remission in the treatment of RA with tocilizumab (TCZ) in daily clinical practice.A total of 240 RA patients who received TCZ were selected from the multicentre Tsurumai Biologics Communication Registry. Predictive baseline factors for remission [28-item DAS (DAS28)2.6] at 52 weeks were determined by logistic regression analysis. To confirm whether the associations varied by the level of baseline disease activity, we also assessed the model including the interaction term (each baseline variable × DAS28).In total, 49.3% of the study participants used MTX with TCZ. Even after controlling for the baseline DAS28, shorter disease duration (≤3 year) [odds ratio (OR) 3.58 (95% CI 1.81, 7.07)], less structural damage [Steinbroker stage ≤II, OR 2.33 (95% CI 1.32, 4.12)] and concomitant prednisolone use [OR 0.38 (95% CI 0.21, 0.68)] showed significant predictive values for remission. Concomitant MTX use failed to show a significant association with remission, whereas a significant interaction was observed among concomitant MTX use × DAS28 (P = 0.006). In patients with high baseline disease activity (DAS285.1), concomitant MTX use was associated with increased odds for remission [adjusted OR for all baseline variables 2.54 (95% CI 1.11, 5.83)], while no association was indicated between them in patients with low to moderate baseline disease activity (DAS28 ≤ 5.1).Concomitant MTX use is an important component of TCZ treatment for RA patients with high disease activity.

The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab, and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy. Patients at baseline had a mean age of 58.7 years, mean disease duration of 9.8 years, and mean clinical disease activity index (CDAI) of 22.4. There was no significant difference between the three drugs, except in rheumatoid factor positivity. Retention rates for abatacept, tocilizumab, and etanercept treatment at 52 weeks were 72.0, 89.5 and 84.6 %, respectively. The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs. Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations. Our results show that patients treated with abatacept, tocilizumab, and etanercept achieved a high response rate with no significant differences in drug retention rates and clinical efficacy. These drugs represent good therapeutic options for patients with RA who are refractory to anti-TNF monoclonal antibody therapy.

Objective We previously reported that depression and inflammation have independent effects on pain severity in patients with rheumatoid arthritis (RA). Alexithymia is a personality trait characterized by deficits in cognitive processing and regulation of emotions. A broad association between alexithymia and various health problems has been suggested, including depression, inflammation, and pain. The objective of this study was to examine the independent influence of alexithymia on pain perception and its relationship to depression and inflammation. Methods We evaluated 213 RA outpatients who completed self-administered questionnaires, including the Beck Depression Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were measured to quantify inflammation severity. Results An initial significant positive association between the TAS-20 score and pain severity (P = 0.01) lost significance after controlling for BDI-II score and CRP level using regression analysis. An interaction was observed among alexithymia, depression, and inflammation with regard to perceived pain. Among those without alexithymia, pain severity increased linearly with the CRP tertile levels regardless of the presence of depression (P < 0.001 for trend). No linear association between pain severity and CRP level was observed among those with alexithymia. Moreover, depressed patients with alexithymia (BDI-II score ≥14 and TAS-20 score ≥61) reported severe pain even at low CRP levels. Conclusion Alexithymia might have a substantial role in pain perception as well as depression in patients with RA. A biopsychosocial approach is essential to achieve better pain control.

Super-resolution techniques have been widely used in fields such as television, aerospace imaging, and medical imaging. In medical imaging, X-rays commonly have low resolution and a significant amount of noise, because radiation levels are minimized to maintain patient safety. In this paper, we propose a novel super-resolution method for X-ray images, and a novel measurement algorithm for treatment of rheumatoid arthritis (RA) using X-ray images generated by our proposed super-resolution method. Moreover, to validate measurement accuracy for our proposed algorithm, we make a model for measurement algorithm about joint space distance using a 3D printer, and X-ray images are obtained to photograph it. Experimental results show that high quality super-resolution images are obtained, and the measurement distances are measured with high accuracy. Therefore, our proposed measurement algorithm is effective for RA medical examinations.

The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks.One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels.Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks.Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.

The goal of treating rheumatoid arthritis (RA) should be remission, for which a new definition was proposed in 2011. To determine which patients can achieve the new Boolean-based definition of remission in clinical practice, we analyzed factors associated with remission in 123 patients who received tocilizumab for 52 weeks. We found that patients with short disease duration (

Objective Whether the Boolean-based American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for rheumatoid arthritis (RA) including patient-reported outcome measures (PROMs) for remission are strict for use in daily clinical practice is controversial. This study aimed to clarify the differences in the remission status defined by the criteria, including and excluding PROMs, and to identify the baseline predictors of long-term prognosis using 7-year follow-up data. Method A total of 103 RA outpatients completed the baseline and 7-year follow-up questionnaire surveys. Pain visual analogue scale (VAS) of ≤ 1/10 was used as a PROM criterion for remission. Results Only 10 patients achieved full-remission, whereas 18 met the partial-remission criteria excluding PROM at baseline. Although 70.0% of those who achieved full remission at baseline had full or partial remission status, 77.8% of those with partial remission were categorized as having no remission at 7 years. Significant baseline differences in the remission status at 7 years were observed with regard to disease duration, pain VAS, and physical function (Short Form 36 [SF-36]). Stepwise logistic regression analysis adjusted for age and sex identified disease duration and general health perception (SF-36) as independent predictors of full-remission. Conclusion Remission criteria including PROMs are stringent but important to achieve sustained remission. Early intensive treatment and efforts to improve patients’ health perceptions may result in better prognosis for RA.

We evaluated radiographic change in the cervical lesions of 47 RA patients receiving continuous infliximab therapy for at least 1 year. Infliximab treatment had been initiated between November 2003 and December 2007. Patients who were progressive and non-progressive in terms of RA cervical lesions were compared. Matrix metalloproteinase 3 (MMP3) values improved significantly only in non-progressive patients within the 1-year treatment window. Cervical lesion progression was suppressed in 19 of the 23 patients (83%) showing a good response to infliximab treatment and occurred in 16 of the 24 patients (67%) showing a moderate response. This difference was shown to be significant by the Fisher's exact test (p = 0.002). In the well-responding patients (n = 23) and moderately responding patients (n = 24), the respective changes in the cervical lesion parameters within 1 year were: atlanto-dental interval, 0.17 +/- 0.49 and 0.54 +/- 0.58 mm (p = 0.013); spinal cord, -0.17 +/- 0.49 and -0.54 +/- 0.59 mm (p = 0.025); Ranawat value, -0.09 +/- 0.29 and -0.42 +/- 0.65 mm (p = 0.032). Based on these results, we conclude that infliximab treatment can be used to suppress the progression of rheumatoid arthritis (RA) cervical lesions. It is possible that response to infliximab and MMP3 values can be used to predict the progression of these cervical lesions.

Objective.To determine the effects of concomitant methotrexate (MTX) on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with rheumatoid arthritis (RA) during longterm treatment with tumor necrosis factor (TNF) inhibitors.Methods.A total of 155 patients with RA (310 knee joints) received TNF inhibitors at our institute between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or swollen) knee joints in 68 patients were retrospectively studied over the course of a minimum of 5 years of followup. The median (interquartile range) followup period was 8.1 (7.0–9.3) years. All data were analyzed using the knee joint as the statistical unit of analysis. TKA during treatment with TNF inhibitors was used as the outcome variable in predictive analyses. The cumulative incidence of TKA was compared by concomitant or no MTX use (MTX±).Results.There were 79 subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates, the cumulative incidence of TKA for the MTX+ group was significantly lower than that for the MTX− group (24% vs 45% at 5 yrs, respectively, p = 0.035). Multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX (HR 0.44, 95% CI 0.22–0.89), Larsen grade (HR 2.93, 95% CI 1.94–4.41), and older age at baseline (HR 1.04, 95% CI 1.01–1.08) were independent predictors of TKA.Conclusion.Concomitant MTX reduces the incidence of TKA by 56% in patients with RA during longterm treatment with TNF inhibitors.

This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan.

Objective.Assessing retention rate and risk factor for drug discontinuation is important for drug evaluation. We examined a 3-year retention rate and the risk factor for discontinuation due to insufficient efficacy (IE) and adverse events (AE) in Japanese patients with rheumatoid arthritis (RA) who are receiving etanercept (ETN).Methods.Data were collected from 588 patients treated with ETN as a first biologic from the Tsurumai Biologics Communication Registry. Baseline characteristics for the incidence of both IE and AE were analyzed using the Cox proportional-hazards regression model. Patients were divided into groups based on age and concomitant methotrexate (MTX). Drug retention rates were calculated using the Kaplan-Meier method and compared among groups using the log-rank test.Results.ETN monotherapy without concomitant MTX [MTX(–)] was significantly related to a higher incidence of discontinuation due to IE [hazard ratio (HR) = 2.226, 95% CI 1.363–3.634]. Older age and MTX(–) were significantly related to a higher incidence of discontinuation due to AE [HR = 1.040, 1.746, 95% CI 1.020–1.060, 1.103–2.763, respectively]. The MTX(–)/≥ 65 years group had the lowest retention rate (p < 0.001). The discontinuation rate due to IE was lower in the MTX(+)/< 65 years group compared to < 65 years/MTX(–), ≥ 65 years/MTX(–) group (p = 0.006, p < 0.001, respectively). The discontinuation rate due to AE was highest in the MTX(–)/≥ 65 years group (p < 0.001).Conclusion.Our findings suggest that the risk of discontinuation due to IE was high in the patients who did not use concomitant MTX and that the risk of discontinuation due to AE was high in elderly patients who did not use concomitant MTX.

Background According to Treat to target strategy, we have to consider changing the treatment in 3-6 months. Clinical course of RA treatment should be important to predict further outcome and to decide the therapy management in clinical practice. Objectives We aimed to assess the efficacy of abatacept (ABT) in rheumatoid arthritis (RA) patients in switching and identify predictive factors at baseline for low disease activity (LDA) or remission using data from a multicenter registry, Tsurumai Biologics Communication Registry (TBCR). Methods From 2,771 RA patients registered until 2013, 225 patients with moderate or high disease activity received ABT were selected [switching for biologics failure; n=100 and naive; n=125]. We compared clinical course and baseline characteristics between biologics-naive and switching patients who achieved LDA. Predictive factors for LDA achievement were determined by multivariate logistic regression analysis in each group. The best cut-off of DAS28-CRP until 24 weeks for LDA achievement at 52 weeks was determined using Receiver operating characteristics (ROC) curve. Results Baseline characteristics of study population (n=225) was mean age; 64.7yeras, disease duration; 11.5 years and baseline DAS28-CRP; 4.70, concomitant MTX use; 49.3% (mean dose; 7.3 mg/week). The biologics-naive patients could achieve LDA at 52 weeks significantly more than in biologics-switching patients (56.0% vs 23.0%, p Conclusions In switching to ABT, disease activity at 12weeks and clinical response up to 12 weeks were important information for prediction of long-term outcome. Disclosure of Interest T. Kojima Grant/research support from: Takeda Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation., Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Abbvie, Bristol-Myers Squibb, Pfizer, Chugai Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation, N. Takahashi: None declared, A. Kaneko Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, Chugai Pharma, Abbott, Bristol-Myers Squibb, UCB, Janssen, and Pfizer, D. Kida: None declared, Y. Hirano Speakers bureau: AbbVie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, and Bristol-Myers Squibb, T. Fujibayashi: None declared, Y. Yabe: None declared, H. Takagi: None declared, T. Oguchi: None declared, H. Miyake: None declared, T. Kato: None declared, T. Watanabe: None declared, M. Hayashi: None declared, T. Shioura: None declared, Y. Kanayama: None declared, K. Funahashi: None declared, S. Asai: None declared, Y. Yoshioka: None declared, K. Terabe: None declared, T. Takemoto: None declared, N. Asai: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan., Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.

Background The presence of rheumatoid factor (RF) plays an important role in diagnosis for patients suspected with rheumatoid arthritis (RA) [1]. However, it remains unclear whether RF positivity is related to the effects of treatment with biologic disease-modifying antirheumatic drugs (DMARDS). Objectives The objective of the current study was to determine whether RF positivity was associated with the effects of treatment with biologic DMARDS among bio-naive RA patients. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; those with prior exposure to biologic DMARDS were excluded. The RF status was divided into negative (0–15 IU/ml) or positive (>15 IU/ml). Multivariate logistic regression analysis was used to assess the association between RF positivity and the possibility of sufficient response to biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, whether or not tumor necrosis factor inhibitor had been used, baseline use of methotrexate (MTX) and glucocorticoids, and baseline stage and class as defined by the Steinbrocker classification. Results The demographic and disease characteristics of the patients at baseline were comparable between RF-negative (n=120) and RF-positive (n=557) groups. The mean age was 57 years; 81% were women. Patients had longstanding RA (mean 9.3 years), and the baseline DAS28 was 5.1. Among the patients, 80% and 61% received MTX and glucocorticoids, respectively. A good response as per EULAR response criteria was identified in 73 (60.8%) RF-negative patients and 268 (48.1%) RF-positive patients. The crude OR for the association between RF positivity and the possibility of good response as per EULAR response criteria was 0.60 (95% CI 0.40–0.89) compared with RF negativity. After adjustment for the aforementioned covariates, RF-positivity was associated with a decreased possibility of good response to biologic DMARDS compared with RF-negativity (OR 0.64, 95% CI 0.41–0.98). Conclusions This study demonstrated that RF-positivity was independently associated with a decreased possibility of good response to biologic DMARDS in bio-naive RA patients. References P.Y. Chang, C.T. Yang, C.H. Cheng, K.H. Yu, Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor in patients with rheumatoid arthritis, Int J Rheum Dis, (2015). Disclosure of Interest None declared

Background Abatacept is a new class of biologic agent for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86. Although some clinicians feel that the rapidity of treatment response of abatacept is slower than that of tumor necrosis factor (TNF)-inhibitors, some patients can respond to abatacept treatment quite rapidly. Recently, some reports have been published regarding the positive association between sero-positivity for anti-citrullinated protein antibody (ACPA) and clinical efficacy of abatacept in RA patients (1). Objectives The aim of this study was to demonstrate the effect of double-seropositivity for ACPA and rheumatoid factor (RF) on the rapidity of treatment response of abatacept using data from a Japanese multicenter registry system for RA patients treated with biologic agents. Methods Participants were selected from the consecutive 508 RA patients treated with abatacept who were registered in the Tsurumai Biologics Communication Registry (TBCR). We excluded the patients with previous biologic agent treatment history since it has been already reported as an independent factor affecting the clinical efficacy of abatacept (2). A total of 146 biologics-naive and ACPA positive patients with baseline data of RF were included in this study. We compared the proportion of patients that achieved good EULAR response at 24 weeks between the RF negative and RF positive (>20 U/ml) group within the ACPA positive patients. We defined the ACPA positive as >13.5 U/ml of anti-CCP antibody (3 times cutoff value) to ensure that the positivity was reasonably sure. Results In the ACPA positive patients, the percent decreasing of DAS28-CRP scores in the RF positive group were significantly greater than those in the RF negative group at all time points (Figure A, e.g. -32.3 vs -12.6% at 24 weeks, p Conclusions We clearly demonstrated that the positive association of the double-seropositivity for ACPA and RF with the rapid and good clinical response for abatacept in the biologics-naive RA patients. This new clinical evidence regarding the effect of double-seropositivity is the valuable real-world data for the prediction of clinical efficacy of abatacept in daily clinical practice. References Gottenberg JE, Ravaud P, Cantagrel A, Combe B, Flipo RM, Schaeverbeke T, et al. Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the 9Orencia and Rheumatoid Arthritis9 registry. Ann Rheum Dis. 2012;71(11):1815–9. Takahashi N, Kojima T, Terabe K, Kaneko A, Kida D, Hirano Y, et al. Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients. Mod Rheumatol. 2013;23(5):904–12. Disclosure of Interest N. Takahashi Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, Takeda Pharma, Bristol-Myers Squibb, T. Kojima Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, Takeda Pharma, Bristol-Myers Squibb, K. Funahashi Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, Takeda Pharma, Bristol-Myers Squibb, N. Ishiguro Grant/research support from: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, Takeda Pharma, Bristol-Myers Squibb, Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, Takeda Pharma, Bristol-Myers Squibb

Background Cartilage loss is irreversible progress, so physicians have to find the detection of joint space narrowing as early as possible. It is stated that physical disability in rheumatoid arthritis (RA) is associated with joint space narrowing rather than erosion [1], so early detection of progressive joint damage is the most important. But in DICOM which is the international standard for medical images, 1 pixel on radiographic images is 0.10 to 0.15 mm, so the detection of the change which is lower than that is impossible.To solve this problem, we previously developed new method measuring the joint space distance with the X-rays image which performed super-resolution image processing [2]. However, we did not validate the measured value by our methods. Objectives To validate the measurement of joint space distance by using super resolution image and curve fitting methods. We also evaluated whether the focus-film distance affected the measured value. Methods We producted phantom model (PM) of joint space that expressed metacarpophalangeal joint space 1mm by using 3D printer.The super-resolution images of PM with radiographs by using total variation regularization and shock filter were prepared (Fig. 1). We measured the distance of joint space by three methods, 1) conventional measurement; distance between two points, 2) measurement by using normal vector from the top of joint surface of phalanx bone, 3) measurement using joint space area calculated by integration method. Each method processed on MATLAB®. 2), 3) methods were processed by curve fitting method which create parabolic curve by choosing some points of joint surface.We measured the distance ten times to adjust the error of measurement.We took radiographs with the focus-film distance under conditions of 90cm, 100cm, 110 cm, respectively. Results Between the two points method, normal line method and integration method, the mean (standard deviation) of measured value under focus-film distance 90 cm was 1.033 (0.018), 0.964 (0.017), 0.939 (0.009), respectively. Under focus-film distance 100 cm, it was 0.963 (0.031), 0.969 (0.032) ,0.943 (0.025), respectively. Under focus-film distance 110 cm, it was 1.019 (0.026), 0.964 (0.018), 0.943 (0.015) , respectively. There were no significant differences with measured value between three methods under each focus-film distance. There were also no significant differences with each focus-film distance (Fig. 2). Conclusions The measured value was not affected by a difference of the focus-film distance between 90cm to 110cm.We obtained the measured value, 0.937 – 0.970 by two methods, which were equal to 1mm of PM.The standard deviation was less than 0.032mm. We validated the measurement accuracy of curve fitting methods. We suggested that the possibility of early detection with joint space narrowing in rheumatoid arthritis patients by using super resolution image and curve fitting methods. References Ann Rheum Dis. 2011 May;70(5):733–739. IEEE Global Conference on Consumer Electronics (GCCE2013) 2013;: 447 - 448 Disclosure of Interest K. Funahashi: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation,Abbott, Bristol-Myers Squibb and Pfizer, N. Takahashi Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation,Abbott, Bristol-Myers Squibb and Pfizer, S. Asai: None declared, T. Takemoto: None declared, N. Asai: None declared, T. Watanabe: None declared, T. Goto: None declared, M. Shimizu: None declared, H. Kariya: None declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation,Abbott, Bristol-Myers Squibb and Pfizer

Background Concomitant glucocorticoids effectively increase remission rate in patients with early rheumatoid arthritis (RA) treated with synthetic DMARDs. 1 However, it remains unclear whether concomitant glucocorticoids have additive effects over biologic agents after achieving remission in the patients with RA. Given that drug retention reflects a good balance between effectiveness and tolerability, assessing the retention rate and reasons for discontinuation is important for drug evaluation. Objectives To compare retention rate of biologic agents for the patients who achieved clinical remission with and without concomitant glucocorticoid treatment [GC(+) and GC(−) groups, respectively], and investigate the predictors of drug discontinuation due to insufficiency in the GC(+) group. Methods A cohort study was performed using a multicentre registry. A total of 404 patients with RA achieved clinical remission defined as a DAS28-CRP Results There was good balance across all baseline characteristics after propensity score matching (Table 1). Six of the 128 patients (4.7%) in the GC(−) group discontinued the first biologic agents due to insufficiency during the follow-up period, while 31 of the 128 patients (24.2%) in the GC(+) group did so. According to Kaplan-Meier estimates, the discontinuation rate due to insufficiency for the GC(+) group was significantly higher than that for the GC(−) group (37% vs. 7%, respectively, at 5 years, P P =0.676) (Fig. 1B). Multivariate analysis using Cox proportional hazards models revealed that Steinbrocker stage (III+IV vs. I+II) (HR: 3.37, 95% CI: 1.09–10.44, P =0.035) independently predicted drug discontinuation due to insufficiency in the GC(+) group. Conclusions The patients who achieved remission with concomitant glucocorticoid treatment, especially with Joint destruction existing at achieving remission, had a high risk of subsequent discontinuation of biologic agents due to insufficiency. References Svensson B, et al. Arthritis Rheum 2005;52:3360–70. Disclosure of Interest S. Asai Speakers bureau: Eisai Pharma Corporation, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, AbbVie, Bristol-Myers Squibb, Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma, Chugai Pharma Corporation, N. Takahashi Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, AbbVie, Bristol-Myers Squibb, Janssenn Pharmaceutical Companies, UCB Japan Co, Chugai Pharma Corporation, K. Funahashi: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical,Kaken Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, AbbVie, Bristol-Myers Squibb, Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma, Chugai Pharma Corporation, Speakers bureau: Daiichi Sankyo, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical,Kaken Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, AbbVie, Bristol-Myers Squibb, Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma, Chugai Pharma Corporation

Background In general, the concomitant use of methotrexate (MTX) and biologic disease-modifying antirheumatic drugs (DMARDS) plays an important role in treatment for bio-naive patients with rheumatoid arthritis (RA). However, it remains unclear whether concomitant use of MTX is related to the effects of treatment with second biologic DMARDS in RA patients for whom first biologic DMARDS therapy have failed. Objectives The objective of the current study was to determine whether, and if so to what extent, concomitant use of MTX was associated with the effects of treatment with second biologic DMARDS, especially in the context of whether or not tumor necrosis factor inhibitor (TNFi) had been used. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; only those switching to second biologic DMARDS therapy were included. Multivariate logistic regression analysis was used to assess the association between MTX use and the possibility of sufficient response to second biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, disease duration, whether or not TNFi had been used in RA treatments with first and second biologic DMARDS, use of MTX in first biologic treatment, and use of glucocorticoids in treatment with second biologic DMARDS. We determined the statistical significance of potential subgroup effect of whether or not TNFi had been used as second biologics by testing the significance of the interaction terms added to our multivariable models. Results The demographic and disease characteristics of the patients at baseline were comparable except for the proportion of TNFi between patients not using MTX (n=49) and those treated concomitantly with MTX (n=122). The mean age was 59 years; 86% were women. Patients had longstanding RA (mean 10.6 years), and the baseline DAS28 was 5.2. Among the patients, 68% received glucocorticoids. The mean dose of MTX was 8.0 mg/week in patients using MTX. The proportion of TNFi was 26.5% in patients not using MTX and 62.3% in those using MTX, respectively. A good response as per EULAR response criteria was identified in 14 (28.6%) patients not using MTX and 58 (47.5%) patients treated concomitantly with MTX. The crude OR for the association between concomitant use of MTX and the possibility of good response as per EULAR response criteria was 2.27 (95% CI 1.11–4.63) compared with nonuse of MTX. After adjustment for the aforementioned covariates, concomitant use of MTX was associated with an increased possibility of good response to biologic DMARDS compared with nonuse of MTX (OR 2.77, 95% CI 1.04–7.36). This multivariable adjusted effect estimate was not modified by whether or not TNFi had been used (P value for interaction greater than 0.05). Conclusions This study demonstrated that concomitant use of MTX was independently associated with an increased possibility of good response to second biologic DMARDS regardless of whether or not TNFi had been used in RA treatment. Disclosure of Interest None declared

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.

We assessed the effect of total large-joint arthroplasty combined with anti-tumor necrosis factor (TNF) therapy for rheumatoid arthritis (RA). We studied 45 RA patients (age 57.91 ± 12.74 years, RA duration 13.43 ± 8.28 years) who underwent total arthroplasty (35 knees, 19 hips, 3 elbows, and 1 ankle) between August 2002 and November 2009. All patients received anti-TNF agents (infliximab, 22; etanercept, 33; adalimumab, 3) during the period of the study (that is, they were being treated with the agents when operated on and postoperatively). The disease activity score 28 (DAS28)-erythrocyte sedimentation rate (mean ± standard deviation) in all patients improved significantly from baseline (just before the operation; 4.32 ± 0.99) to 1 year after the operation (3.35 ± 0.93) in contrast with the finding that the mean DAS28-ESR values had remained unchanged from 1 year before the operation to the baseline. Changes in clinical variables in the 58 cases were investigated at baseline, and at 4, 12, and 52 weeks after the operation. The patients were divided by a median split of baseline demographics into 2 groups for further evaluation. Compared with the high-value groups, those with low C-reactive protein and matrix metalloproteinase-3 values showed better results and had lower disease activity. Overall, the DAS28-ESR in both groups had improved 1 year after the operation. In RA patients who are being treated with anti-TNF agents, large-joint arthroplasty may be beneficial, not only for the relief of pain arising from joint destruction, but also for the systemic reduction of RA activity.

Background Cartilage loss is irreversible progress, so physicians have to catch the detection of joint space narrowing as early as possible. It is stated that physical disability in rheumatoid arthritis (RA) is associated with joint space narrowing rather than erosion [1], so early detection of progressive joint damage is the most important. But in DICOM which is the international standard for medical images, 1 pixel on radiographic images is 0.15mm, so the detection of the change which is lower than that is impossible. Objectives To solve a limitation associated with the resolution, we used radiographic images reconstructed by super-resolution system by utilizing total variation filter combined a shock filter, which is a non-linear filter, to emphasize the edges in images [2]. Theoretically image resolution becomes four times (Fig. 1). We measured the distance between joint space of metacarpophalangeal (MCP) joint and confirmed the validity of the new measurement procedure of the distance between joint space by using super resolution image. Methods We prepared the super resolution-radiographic images processed by total variation filter and a shock filter and cropped the images of MCP joint. We measured the distance between joint space by three methods, 1) conventional measurement; distance between two points, 2) measurement by using normal vector from the top of joint surface of phalanx bone, 3) measurement using joint space area calculated by integration method (Fig. 2). Each method processed on MATLAB®. The 2), 3) methods were processed by curve fitting method which create parabolic curve by choosing some points of joint surface. We performed measurement five times by each method to confirm the accuracy by using super resolution image and standard DICOM image. Results We measured Lt 3rd MCP joint with 49 y.o. female, rheumatoid arthritis patient by each measurement on super resolution image and standard DICOM image. The measurement results are shown in Table 1. It was significantly different between super resolution and normal resolution by two points measurement with f-test. Although it was not significantly different on condition about resolution by the measurement using curve fitting methods with f-test, the value with super resolution image tended to be smaller than that with normal resolution. Conclusions The accuracy of measuring the joint space distance of MCP joint was improved by using super-resolution image. Curve fitting method was also supposed to be useful about the evaluation of joint space narrowing. This result suggested that it is possible to detect the change less than 0.1mm beyond the limitation of DICOM image. References Ann Rheum Dis. 2011 May;70(5):733-739. IEEE Global Conference on Consumer Electronics (GCCE2013) 2013;: 447-448. Disclosure of Interest K. Funahashi: None declared, T. Kojima Grant/research support from: Takeda Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation., Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Abbvie, Bristol-Myers Squibb, Pfizer, Chugai Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation, N. Takahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd,Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai PharmaceuticalCo. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., T. Goto: None declared, M. Shimizu: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.

Background Tocilizumab (TCZ) is effective for rheumatoid arthritis (RA) patients with inadequate responses to tumor necrosis factor (TNF) antagonists. Previous report showed that among RA patients who were switched to a second TNF antagonist, the reasons for stopping a second drug were related to the reasons for stopping the first drug 1 . However, it has not yet been established whether the type of failure that motivated the switch from TNF antagonists influences the retention of TCZ. Objectives The present study was undertaken to investigate the relationship between the retention of TCZ and the reason for discontinuation of previous TNF antagonists in RA patients. Methods This study included 191 RA patients who switched from TNF antagonists to TCZ therapy in Tsurumai Biologics Communication Registry (TBCR). The retention rates of TCZ at 2 years were calculated by the Kaplan-Meier method and compared using the log-rank test between two groups divided by the reasons for discontinuation of previous TNF antagonists (162 patients with inefficacy; LOE group, and 29 patients with adverse events; AE group). Results There were no differences between the two groups in terms of age, disease duration, TNF antagonist before switch, concomitant MTX use, or DAS28-ESR at the switch to TCZ therapy. The discontinuation rate of TCZ at 2 years in LOE group was significantly lower compared with AE group (p=0.023, log-rank test). No significant differences existed between the two groups for treatment discontinuation due to inefficacy (p=0.476). On the other hand, the discontinuation rate due to adverse events was significantly lower for LOE group compared with AE group (p=0.001). Conclusions RA patients who switched from TNF antagonists due to inefficacy to TCZ have high rates of continuation. References Hyrich KL, et al. Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum. 2007 Jan;56(1):13-20. Disclosure of Interest N. Asai: None declared, Y. Yabe: None declared, T. Kojima Grant/research support from: Takeda Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation., Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Abbvie, Bristol-Myers Squibb, Pfizer, Chugai Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation., N. Takahashi: None declared, K. Funahashi: None declared, S. Asai Speakers bureau: Eisai Pharma Corporation., T. Takemoto: None declared, K. Terabe: None declared, Y. Yoshioka: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan., Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.

Background Abatacept (ABT) is a biologic drug and has been available for rheumatoid arthritis (RA) patients since 2010 in Japan. Although we have some reports describing the short-term clinical results of ABT [1], there has been little evidence showing the long-term results of ABT. Positivity for anti-CCP peptide has been reported that it is associated with a better response to ABT at 6 months [2]. There have been few reports describing the association of rheumatoid factor with the long-term clinical results represented by drug retention rate. Objectives The aim of this study is to demonstrate whether the positivity for rheumatoid factor is associated with the short-term (52 weeks) clinical response to ABT and the long-term (4 years) drug retention rate of ABT using data from a Japanese multicenter registry system for RA patients treated with biological DMARDs. Methods Participants were consecutive 508 patients with RA who were prospectively registered in the Tsurumai Biologics Communication Registry and treated with ABT. Demographic data and the following parameters of disease activity were collected; TJC, SJC, patient global assessment, ESR, and serum CRP at baseline, 4, 12, 24, and 52 weeks. The last observation carried forward (LOCF) method was used in each analysis. Survival analysis was performed with the Kaplan-Meier method and log-rank test. We compared these clinical indices between the patients with and those without RF positivity. Results At baseline, mean age was 65.1 years, disease duration was 13.1 years, and DAS28-CRP was 4.36. Of the 508 patients, 78.8% was female, 77.5% was RF positive (>20 mg/dl), and 42.7% had prior biologics history (Bio-switch). Percent change of DAS28-CRP was significantly greater in the RF positive group from 4 weeks throughout 52 weeks (p Overall drug retention rate was 60.0% in the RF negative and 77.5% in the RF positive group at 4 years (Fig. 2a). Discontinuation rate due to insufficient efficacy (Insufficiency) was 27.2% in the RF negative and 15.3% in the RF positive group (Fig. 2b). Discontinuation rate due to adverse events was similar between the groups (Fig. 2c). Within the bio-switch patients, the RF negative group demonstrated significantly higher discontinuation rate due to secondary failure (40.8 vs 11.0%) (Fig. 3b). The hazard ratio (HR) for secondary failure, adjusted for sex, age, disease duration, concomitant MTX and PSL, and baseline DAS28-CRP, was 4.17 (95%CI 1.20-14.45) for RF negative versus RF positive. On the other hand, RF positivity did not affect the discontinuation rate in the Bio-naive patients (Fig. 3a). Conclusions We found that RF positivity was associated with better short-term response to ABT. We also found that RF positivity significantly improve the long-term incidence rate of discontinuation due to secondary failure in the bio-switch patients. It is necessary to establish the strategy for additional therapeutic intervention, such as concomitant drugs, in this patients group to improve the short- and long-term clinical results of ABT. References Takahashi, et al. Rheumatology (Oxford) 2014. in press Gottenberg JE, et al. Ann Rheum Dis 2012;1815. Disclosure of Interest N. Takahashi: None declared, T. Kojima Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., K. Funahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan

Background According to Treat to target strategy, we have to consider changing the treatment in 3-6 months. Clinical course of RA treatment should be important to predict further outcome and to decide the therapy management in clinical practice. Objectives We aimed to identify predictive factors for low disease activity (LDA) achievement and for clinical course to LDA in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT) with low dose or no methotrexate (MTX) using multicenter Tsurumai Biologics Communication Registry. Methods From 2,771 RA patients registered in the Tsurumai Biologics Communication Registry until 2013, 76 with moderate or high disease activity who received ABT in switching from TNFis were selected. Relationship between response until 24 weeks and achievement of LDA or remission at 52 weeks was explored using ROC curve. The association of previous TNFis to achievement of LDA or remission at each follow-up period (4-52w) was also determined by adjusting factors at baseline with multivariate logistic regression analyses. Results Baseline characteristics of study population (n=76) was mean age; 63.4years, disease duration; 13.2 years and baseline DAS28-CRP; 4.90, concomitant MTX use; 52.6% (mean dose; 7.8 mg/week). Previous TNFis were as follows; infliximab (IFX) 14 cases, etanercept (ETN) 41 cases, adalimumab (ADA) 21 cases. DAS28 significantly improved to 3.58 at 52 weeks; 26.3% of patients achieved LDA (Fig.1). DAS28-CRP at 4 and 12 weeks had significant association with LDA at 52 weeks (AUC; 0.74, and 0.86, respectively) while that at baseline did not based on ROC curves (Fig. 2). LDA achievement at 52 weeks was comparable among previous TNFis while there were significant differences in LDA achievement rate and DAS28-CRP at 12weeks by previous TNFis (Fig. 3). Multivariate analysis confirmed that DAS28-CRP Conclusions Clinical course until 12 weeks is important to predict long-term outcome even in switching from TNFi to ABT. The clinical course to LDA achievement could be influenced by previous TNFi. Disclosure of Interest T. Kojima Grant/research support from: Takeda Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation, Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Abbvie, Bristol-Myers Squibb, Pfizer, Chugai Pharma Corporation, Janssen Pharmaceutical, and Astellas Pharma Corporation, N. Takahashi: None declared, A. Kaneko Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, Chugai Pharma, Abbott, Bristol-Myers Squibb, UCB, Janssen, and Pfizer, D. Kida: None declared, Y. Hirano Speakers bureau: AbbVie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, and Bristol-Myers Squibb, T. Fujibayashi: None declared, Y. Yabe: None declared, H. Takagi: None declared, T. Oguchi: None declared, H. Miyake: None declared, T. Kato: None declared, T. Watanabe: None declared, M. Hayashi: None declared, T. Shioura: None declared, Y. Kanayama: None declared, K. Funahashi: None declared, S. Asai: None declared, Y. Yoshioka: None declared, K. Terabe: None declared, T. Takemoto: None declared, N. Asai: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan., Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.