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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.

To provide further insights into non-genomic action of thyroid hormone (T3), we investigated whether Src is under control of T3 in primary calvarial osteoblasts prepared from neonatal mice. Treatment of the cells with T3 rapidly decreased Src Y416 autophosphorylation, followed by the decrease of phosphorylated extracellular signal-regulated kinases, suggesting that T3 non-genomically suppresses Src activity. Furthermore, this T3 effect was rapid and persistent, and was associated with the increased expression of osteocalcin (OC). To confirm the contribution of Src to the effect of T3 on OC expression, a constitutively active Src (Y527F) was overexpressed in osteoblasts. In such cells, Y416 phosphorylation was markedly increased even in the presence of T3, and T3-dependent expression of OC was markedly attenuated. The present study demonstrates a novel, non-genomic action of T3 in primary mouse osteoblasts, by which T3 suppresses Src thereby stimulating OC expression.

We investigated possible involvement of prostaglandin (PG) E2 in regulation of AMP-activated protein kinase (AMPK). When osteoblastic MG63 cells were cultured in serum-deprived media, Thr-172 phosphorylation of AMPK alpha-subunit was markedly increased. Treatment of the cells with PGE2 significantly reduced the phosphorylation. Ser-79 phosphorylation of acetyl-CoA carboxylase, a direct target for AMPK, was also reduced by PGE2. On the other hand, PGE2 reciprocally increased Ser-485 phosphorylation of the alpha-subunit that could be associated with inhibition of AMPK activity. These effects of PGE2 were mimicked by PGE2 receptor EP2 and EP4 agonists and forskolin, but not by EP1 and EP3 agonists, and the effects were suppressed by an adenylate cyclase inhibitor SQ22536 and a protein kinase A inhibitor H89. Additionally, the PGE2 effects were duplicated in primary calvarial osteoblasts. Together, the present study demonstrates that PGE2 negatively regulates AMPK activity via activation of protein kinase A signaling pathway.

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.

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.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.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 (P0.001). 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).Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.

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.

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.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.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 (P0.001 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.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.

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.

Background It is stated that low-dose glucocorticoids (GCs) should be considered as part of the initial treatment strategy with rheumatoid arthritis (RA), but should be tapered as rapidly as clinically feasible in overarching principles with EULAR recommendations 2013 [1]. Objectives To assess treatment outcome tapering glucocorticoids (GCs) in accordance with EULAR recommendations 2013 with Tocilizumab (TCZ) treatment for 24 months by using multi-center registry for the treatment of RA with biologics in Japan (Tsurumai Biologics Communication Registry; TBCR) [2]. Methods 276 RA patients treated with TCZ for at least 24 months in Nagoya University Hospital and 12 affiliated institutes (TBCR Study Group) were enrolled in this study. We compared three groups which are TCZ treatment without GCs at the baseline (n=95), with stopping GCs by 24 months (n=78) and with persistence of GCs for 24 months (n=103). Difference in baseline characteristics was summarized in Table.1. We assessed disease activity with DAS28-ESR, retention rate of drug continuity with Kaplan-Meier method for 24 months and the proportion of achievement with low disease activity and remission on DAS28-ESR. The last observation carried forward (LOCF) method was used in each analysis. Results In GCs(-) group, GCs withdrawal group and GCs continuation group, the values of DAS28-ESR at the baseline were 5.39, 5.57, 5.77, respectively. Although each group significantly improved in DAS28-ESR, it is significantly different in the three groups at 24 months by one-way ANOVA (Fig. 1). The continuation rate of TCZ treatment associated with inadequate response (IR) and adverse events (AEs) was significant difference between GCs withdrawal group and GCs continuation group (Log-rank test: p=0.007; IR p=0.006; AEs) (Fig. 2). The two years continuation rate associated with IR is 88.0, 95.8, 82.6% in each group. The proportion of achievement with low disease activity and remission on DAS28-ESR is 65.5, 67.1, 45.1% in each group at 24 months (Fig.3). Conclusions We confirmed that the good outcome of TCZ treatment by stopping GCs with effectiveness and safety. References Ann Rheum Dis. 2014 Mar;73(3):492-509. Mod Rheumatol. 2012 Jun;22(3):339-45. Disclosure of Interest K. Funahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma, 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., S. Asai: None declared, Y. Yoshioka: None declared, T. Takemoto: None declared, K. Terabe: None declared, N. Asai: None declared, Y. Yabe: 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 Various tumour necrosis factor (TNF) inhibitors in combination with methotrexate (MTX) have been shown to be significantly superior to monotherapies of each agent in inhibiting radiographic progression of small joints in patients with rheumatoid arthritis (RA). Damage to large joints, especially weight-bearing joints such as the knee, has a larger impact on functional disability than damage to small joints. Accordingly, the evaluation of large weight-bearing joints is important when assessing the efficacy of drug therapy for RA, as is the evaluation of small joints. It is also important to evaluate the long-term inhibitory effect of drug therapy on joint damage. Given that total joint arthroplasty is a common procedure for treating damaged large joints, it can serve as a surrogate for the long-term outcome of large joint destruction in patients with RA. Objectives This study aimed to determine the effects of concomitant MTX on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with RA during long-term treatment with TNF inhibitors. Methods A total of 155 RA patients (310 knee joints) received TNF inhibitors at our institute between May 1, 2005 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 five years of follow-up. The median (IQR) follow-up period was 8.1 (7.0-9.3) years. All data were analysed 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 Subjects were predominantly female (86%), and had a median age of 54 years, disease duration of 8 years and DAS28-CRP of 5.6 at initiation of TNF inhibitors. Based on the Larsen grade of knee joints, 5 joints were categorized as grade 0, 24 as grade I, 26 as grade II, 31 as grade III, 25 as grade IV, and 0 as grade V. Of all subjects, 79 (71%) received concomitant MTX. A total of 33 knee joints underwent TKA during treatment with TNF inhibitors. According to Kaplan-Meier estimates, the incidence of TKA for the MTX (+) group was significantly lower than that for the MTX (-) group ( P =0.035) (Fig. 1). Previous studies reported that age and joint damage existing at baseline was a risk factor for the progression of large joint destruction in patients with RA treated with TNF inhibitors. Interestingly, multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX predicted TKA (hazard ratio: 0.44, 95% confidence interval: 0.22 to 0.89) independently of age and joint damage at baseline (Table 1). Conclusions Concomitant MTX effectively reduces the incidence of TKA in patients with RA during long-term treatment with TNF inhibitors, regardless of age and pre-existing joint damage. Our findings suggest that TNF inhibitors should be used preferentially in combination with MTX to inhibit the progression of large joint destruction as well as small joint destruction, and also strongly support recent EULAR recommendations to commence MTX with all bDMARDs. Disclosure of Interest S. Asai Speakers bureau: Eisai Pharma Corporation, N. Takahashi: None declared, K. Funahashi: None declared, Y. Yoshioka: None declared, T. Takemoto: None declared, K. Terabe: 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., 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

Background In 2011 ACR/EULAR Boolean-based definition of remission in RA, patient global assessment (PGA) is often the limiting factor for reaching remission 1 . The main determinants for the PGA are pain, function, and number of swollen joints 2 . Physical functions will affair clinical remission. Given the tight correlation between physical function and loss of social and economic opportunities 3 , as well as clinical remission, functional remission is also an important goal. Objectives The aim of this study is to investigate the impact of physical function on PGA, and to clarify the predicting factor of functional and clinical remission. Methods 512 RA patients at Nagoya University Hospital were enrolled in this study. Physical function was assessed using Health Assessment Questionnaire (HAQ), disease activity DAS28-CRP, and PGA 0-10 visual analog scale. Results Patients were primarily women (81.4%). Mean age was 60.3±14.0 years, disease duration 13.0±10.4 years, HAQ-DI 0.67±0.75, and DAS28-CRP 2.37±1.02. HAQ-DI was getting worse in correlation with disease activity (r=0.452), and disease duration (r=0.446). In the early stage of RA (duration PGA had a most strong correlation with the HAQ-DI in the components of the DAS28-CRP (r=0.395). Of the patients who were in functional remission (HAQ-DI ≤0.5), mean PGA was 0.51, of the patients whose HQA-DI >0.5; 4.2 (Fig. 1). 50.3% of the former fulfilled PGA 0 or 1, on the other hand, only 16.0% of the latter fulfilled PGA 0 or 1 (Fig. 2). 277 patients fulfilled swollen joint count, tenderness joint count, and CRP 1 or less.46.2% fulfilled Boolean-based remission, and 53.8% fulfilled three of four Boolean criteria except PGA. Mean HAQ-DI was the former 0.19, the latter 0.67, which showed a significant difference (Fig. 3). Cut off value was HAQ-DI=0.18 that satisfies PGA 0 or 1 by Receiver Operating Characteristic analysis of the 277 patients fulfilled swollen joint count, tenderness joint count, and CRP 1 or less (Fig. 4). Multivariate analysis revealed that disease duration independently predicted HAQ-DI≤0.18. Conclusions Physical function had an impact on PGA. Physical function was associated with disease activity, especially in the early stage. Cut off value that satisfies PGA 0 or 1 was HAQ-DI =0.18, which was stringent than the HAQ remission (≤0.5). Given that HAQ-DI was getting worse in correlation with disease duration, and disease duration independently predicted HAQ-DI≤0.18, early aggressive treatment is needed to achieve functional remission. References Studenic P, Smolen JS, Aletaha D. Near Misses of ACR/EULAR criteria for remission: effects of patient global assessment in Boolean an index-based definitions. Ann Rheum Dis 2012;71:1702-1705 Studenic P, Radnner H, Smolen JS, Aletaha D. Discrepancies between patients and physicians in their perceptions of rheumatoid disease activity. Arthritis Rheum 2012;64:2814-2823 Strand V, Khanna D. The impact of rheumatoid arthritis and treatment on patients9 lifes. Clin Exp Rheumatol 2010;28:S32-40 Disclosure of Interest T. Watanabe Speakers bureau: Janssen Pharmaceutical, 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, N. Takahashi: None declared, K. Funahashi: None declared, S. Asai Speakers bureau: Eisai Pharma Corporation, T. Takemoto: None declared, N. Asai: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical

Background Abatacept (ABT), a selective T-cell co-stimulation modulator, is a new biologic drug and has been available for rheumatoid arthritis (RA) patients since 2010 in Japan. We have previously reported that concomitant methotrexate (MTX) therapy did not significantly affect the clinical efficacy of ABT [1, 2] using data from our multicenter registry system. Objectives The aim of this study is to confirm whether our initial finding is correct by using propensity score matching analysis. Methods Participants were 419 patients with RA who were prospectively registered in the Tsurumai Biologics Communication Registry, treated with ABT, and followed up for at least 52 weeks. In this study, the probability score was estimated using a multivariate logistic regression model predicting concomitant use of MTX versus no concomitant use of MTX using the following variables: age, gender, disease duration, dose of ABT (mg/kg), concomitant use of PSL, Steinbrocker9s stage, history of previous biological DMARDs therapy, disease activity at baseline (DAS28-CRP, mHAQ score, ESR, and MMP-3). Greedy propensity score matching was implemented (1:1 matching using a caliper of 0.01). The last observation carried forward (LOCF) method was used in each analysis. Survival analysis was performed with the Kaplan-Meier method and the log-rank test. Results Unadjusted analysis consisted of 217 and 202 patients treated with and without concomitant MTX treatment, respectively. The propensity score adjusted analysis consisted of 52 patients each. Unadjusted analysis demonstrated that the mean DAS28-CRP score in the patients with MTX was significantly lower than that in the patients without MTX at 4, 12, and 52 weeks (2.83 vs 3.27, p Conclusions Unadjusted analysis using greater number of patients compared to our previous study apparently showed the augmenting effect of concomitant MTX usage for the short-term clinical efficacy of ABT. However, the analysis with careful adjustment using propensity score matching clearly revealed that the augmenting effect of concomitant MTX on the ABT efficacy was practically limited. The long-term retention rate was quite similar even in the unadjusted analysis. We suggest that we can expect the adequate clinical efficacy of ABT therapy even in the patients taking no MTX concomitantly. References Takahashi N, et al. Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients. Mod Rheumatol 2013;23:904. Takahashi, et al. Use of a 12-week observational period for predicting low disease activity at 52 weeks in RA patients treated with abatacept: a retrospective observational study based on data from a Japanese multicenter registry study. Rheumatology (Oxford) 2014. in press 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 Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86, and modulating its interaction with CD28. Although some reports demonstrated that concomitant methotrexate (MTX) had little enhancing effect on short-term clinical efficacy of ABT [1,2], there have been only few long-term studies. Objectives We studied whether background MTX treatment enhanced the ABT efficacy after 24 weeks, by using data from Japanese multicenter registry system for RA patients using biological DMARDs. Methods All RA patients who underwent ABT treatment for at least 52 weeks (n=254) in Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Registry Study Group [2]) were enrolled in this study. Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels at baseline, 24 weeks, and 52 weeks. We compared these clinical data between the patients treated without concomitant MTX (ABT-mono, n=130) and those treated with concomitant MTX (ABT-MTX, n=124, mean MTX dose of 7.4 mg/week). The last observation carried forward (LOCF) method was used in each analysis. Results In the baseline characteristic data, the ABT-mono group had higher pulmonary comorbidity rate (21.5 vs 6.5%, p=0.001) compared to the ABT-MTX group while no other clinical parameters showed significant difference including the proportion of patients with previous biological DMARDs history (47.7 vs 47.6, p=0.986) or the all disease activity indices such as DAS28 (4.48 and 4.54). As shown in Fig. 1, top panels, the ABT-MTX group demonstrated statistically significant decreasing of DAS28 from 24 to 52 weeks while no difference in the ABT-mono group. We next studied the patients that still adhered on ABT therapy in spite of their poor clinical efficacy (moderate or high disease activity, DAS28-CRP >2.7) at 24 weeks. Logistic regression analysis identified the concomitant MTX therapy and female as independent predictors of DAS28 category improvement (e.g. high to moderate disease activity) from 24 to 52 weeks (Fig. 1, bottom panel). Conclusions Concomitant MTX therapy significantly decreased the disease activity after 24 weeks, while it seemed not to have enhancing effect on short-term clinical efficacy of ABT. It is true that the ABT efficacy is still significant even in the patients without MTX usage. However, it would be beneficial to use concomitant MTX in most of RA patients without serious comorbidity for MTX usage. References Arthritis Care Res. 2013;65:718. Mod Rheumatol. 2013;23:904. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2346

Background The treatment of RA has improved significantly over the past decade with the introduction of highly effective tumor necrosis factor inhibitors (TNFi). However, these drugs have little or no effect in about 30% of treated patients. In these cases, the disease-modifying antirheumatic drugs (DMARDs) must be switched. According to the European League Against Rheumatism recommendations, patients who do not respond to initial TNFi therapy should switch to a different TNFi or use a different class of biological DMARD (abatacept, rituximab or tocilizumab) [1]. While several studies have reported on switching from TNFi to other biologics [2, 3], no consensus exists on which drug should be chosen. Objectives 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. Methods 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 in the Tsurumai Biologic Communication Registry (TBCR). Patients were divided into three groups based on the biologic they switched to: abatacept (n=25), tocilizumab (n=38) and etanercept (n=26). Changes in clinical parameters were examined at 0, 24, and 52 weeks after the switch. Disease activity was evaluated at each time point using the DAS28-CRP, as well as the CDAI, which included data from the above-mentioned disease parameters. Results 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 at 52 weeks were 72.0%, 89.5% and 84.6%, respectively (Fig. 1). The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs (Fig. 2). Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations (Table 1). Conclusions This study is the first to compare the clinical efficacy of three different classes of biological DMARDs (abatacept, tocilizumab and etanercept) after the first-line anti-TNF agent using a multicenter registry system. 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 offer good therapeutic options in patients with inadequate response to anti-TNF monoclonal antibodies. References Smolen JS, et al. Annals of the Rheumatic Diseases 2010;69:964-75. Leffers HC, et al. Annals of the Rheumatic Diseases 2011;70:1216-22. Hjardem E, et al. Annals of the Rheumatic Diseases 2007;66:1184-9. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1840

Background Rheumatoid arthritis (RA) patients who failed a first biologic agent due to any reasons have the option of switching to a second one along with the strategy of biologic agent treatment. Patients go over switching to the next one at failing their biologic agent. On the other hand, there are some patients who discontinue any biologic agent treatment due to various reasons such as tolerability concern, complications, economic issue, remission and so on. The impact of this concern has been less studied. Objectives The objective of this study was to investigate the reasons and the risk factors for discontinuation any biologic agent in RA patients. Methods In total patients (n=2179) who underwent biologic agent treatment between 2003 and 2011 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group), 1966 patients who were confirmed continuation or discontinuation of biologic agent treatment were enrolled. We analyzed the retention rate of biologic agent treatment and the reasons for discontinuation. To identify the risks for discontinuation, baseline demographics were compared between the continuing group and the disc continuing group using cox hazard regression analysis. Results In total 1966 patients, 1479 patients were administered biologics continuously, 487 patients were withdrew. Table 1 showed the demographic date in total patients. The retention rate was 72% (n=1563) at least 1 year from starting biologics treatment, 68.7% (n=866) at 3 years, 65.6% (n=360) at 5 years. In 327 patients who were confirmed the reasons of discontinuation, the reasons were adverse events in 191 patients, lack of effectiveness in 66 patients, others in 70 patients. Comparison of incidence for discontinuation using cumulative hazard function, the reason of adverse events was significantly higher than others reasons (Fig. 1). To identify o the risks of discontinuation, we used cox hazard model regression in patients who discontinued treatment due to adverse events and lack of effectiveness, the risk factors were over 70 years of age (OR 1.80 [1.31-2.46]), male (OR 1.79 [1.27-2.52]), over 3 of steinblocker class (OR 1.51 [1.12-2.04]). Non concomitant with methotrexate (OR 1.47 [1.06-2.04]) (Fig. 2). Conclusions The most common reason for discontinuation was adverse events. In a numerically greater proportion of patients who discontinued any biologic agent treatment, timing of discontinuation was within a first year from starting treatment. In addition, the risk factors for discontinuation were similar with those of adverse events. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5503

Background The 2010 EULAR Recommendations have been updated last year, abatacept (ABT) has become available as the first biologic agent for patients with RA (1). The long term efficacy and safety of ABT in patients with or without previous biologic therapy has been reported in clinical trials, but still uncertain in clinical routine practice. Objectives The aim of this study was to assess the 2-year outcomes of ABT therapy in biologic naive patients (Naive group) and patients failed to prior biologics (Switch group) in clinical routine practice. Methods All RA patients who were initiated ABT therapy from October 2010 through to October 2011 (n=152) at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communications Registry: TBCR group) were enrolled in this study. We compared disease activities using DAS28 CRP between Naive group (n=66) and Switch group (n=86). Furthermore, discontinuation due to inadequate responses (IRs) and adverse events (AEs) were evaluated. Results In the baseline characteristics data, there was no significant difference between Naive and Switch group, except for age (64.9 vs. 61.9 years old), disease duration (10.4 vs. 14.1 years) and swollen joint count (4.1 vs. 6.5). Disease activities were significantly decreased at week 12 in both groups, and further decreasing were observed continuously (Fig. 1). However, DAS28 CRP values were significantly lower in Naive group (p Conclusions This study demonstrated that the long term efficacy and safety of ABT in clinical routine practice was comparable to that in clinical trials. Interestingly, no adverse event leading to discontinuation was observed after week 24 except one patient. Safety as well as efficacy is an important consideration when initiating intensive treatment, especially in patients with serious comorbidity. Our results suggest that ABT would be beneficial for patients who have complications with careful treatment. References Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2013. Disclosure of Interest M. Hanabayashi: 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: None declared, D. Kida: None declared, K. Funahashi: None declared, S. Hirabara: None declared, S. Asai: None declared, Y. Yoshioka: 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. DOI 10.1136/annrheumdis-2014-eular.2078

Background In the last decade, treatment with tumor necrosis factor (TNF) inhibitors has significantly improved the outcome in patients with rheumatoid arthritis (RA). Recent studies have highlighted drug immunogenicity as a mechanism behind treatment failure. Concomitant immunosupressors, such as methotrexate (MTX), can reduce the production of anti-drug anitibodies (ADA) which might reduce drug efficacy and result in drug discontinuation. Objectives We investigated the effect of concomitant use of MTX on the long-term adherence of etanercept and adalimumab. Methods All eligible patients were registered in the Tsurumai Biologics Communication Registry (TBCR), an RA research consortium that consists of Nagoya University Hospital and 12 affiliated institutes. As of September 2011, 2,176 RA patients treated with biologics are registered in this registry. Seven hundred ninety four RA patients previously unexposed to biological DMARDs were treated with etanercept (n=560) or adalimumab (n=234). Drug discontinuation rates were calculated by Kaplan-Meier method using the end-point of inefficacy or adverse events. Statistical difference between two groups was tested by Log-rank test. Statistical significance was defined as p-value Results Among the etanercept group, the discontinuation rate due to inefficacy were quite similar between the patients with concomitant MTX (n=385) and those without (n=175) (16.8 vs 14.8% at 3 years and 22.2 vs 24.5% at 6 years, p=0.936, Fig. 1a). Conversely among the adalimumab group, the patients with concomitant MTX demonstrated significantly lower discontinuation rate due to inefficacy (13.5 vs 36.2% at 3 years, p=0.014, Fig. 1c). The patients without MTX demonstrated significantly higher discontinuation rate due to adverse events both in the etanercept (p=0.011, Fig. 1b) and adalimumab group (p=0.016, Fig. 1d). The reason for this difference would have included the patients9 background complications for which they could not take MTX therapy. Unfortunately, such information was not available in the registry data. Conclusions It was quite interesting that the concomitant MTX usage did not improve the discontinuation rate due to inefficacy in the patients with etanercept therapy. Production of anti-drug antibodies (ADA) reduces the biological DMARDs effect that can be attenuated by concomitant methotrexate, which reduces ADA frequency. In the case of adalimumab, some previous reports demonstrated that the long-term clinical outcome is strongly dependent on the presence or absence of anti-adalimumab antibodies. On the other hand, some report showed that anti-etanercept antibody is hardly detected. Our current data clearly support these previous data that showed less immunogenicity of etanercept. Thus, we would conclude that the drug immunogenicity should be considered especially for the patients that cannot take concomitant MTX. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1422

Background EULAR recommends that all biologics DMARDs should be used preferentially in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients. The TEMPO study and the JESMR study showed that combination therapy with Etanercept (ETN) plus MTX was significantly superior to ETN alone in inhibiting radiographic progression of the hands, wrists, and forefeet [1, 2]. However, it is still unclear whether concomitant MTX affect inhibiting progression of large joint destruction in RA patients treated with ETN. Total joint replacement is a common procedure for damaged large joint, and it is the essential marker of severe joint destruction in RA patients [3]. Objectives The aim of this study was to investigate the effect of concomitant use of MTX on the incidence of large joint replacement surgery in RA patients treated with ETN. Methods A retrospective multicenter study was performed by using Tsurumai Biologics Communication Registry (TBCR), which consisted of patients who were starting biologic treatments and included baseline characteristics. Of 652 RA patients treated with ETN, 42 patients underwent 58 total joint replacement (34 TKA, 19 THA, 3 TEA, 1 TAA and 1 TSA) during treatment with ETN. The incident rate of total joint replacement was determined by the Kaplan-Meier method. Statistical different was tested by Log-rank test. To identify risk factors for incidence of total joint replacement, impact of baseline clinical variables were analyzed by using Cox proportional hazards regression analysis. Results Patients were predominantly female (83.9%), and had a mean age of 59 years, disease duration of 10.9 years and DAS28-ESR of 5.4 at initiation of ETN. MTX was concomitantly used with 70.4% of the patients. Mean time between initiation of ETN and total joint replacement was 1.5 years. The incident rate of total joint replacement for the patients with concomitant MTX was significantly lower than that for the patients without concomitant MTX (6.7 vs 12.3% at 5years, p=0.032, Figure1). Multivariate analysis identified no concomitant MTX use and age at initiation of ETN as the independent risk factors for incidence of total joint replacement (Table 1). Radiographic data was not available in the registry data though the existing joint damage at baseline would affect the need for total joint replacement. Conclusions This study demonstrated that combination therapy with ETN plus MTX was superior to ETN alone in reducing the incidence of large joint replacement surgery. Our data support the EULAR recommendation. ETN should be used preferentially in combination with MTX to inhibit progression of large joint destruction as well as hand and foot joint destruction. References van der Heijde D. Arthritis Rheum 2006; 54: 1063-74 Hideto Kameda. J Rheumatol 2011; 38: 1585-92 Wolfe F. Arthritis Rheum 1998; 41: 1072-82 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1502

Background After demonstration of effectiveness of anti-tumor necrosis factor (TNF) agents in patients with rheumatoid arthritis (RA), their use has become common practice in treating patients not responding to classical disease modifying anti-rheumatic drugs (DMARDs). Objectives In this paper, we studied the long-term clinical outcome of infliximab, which is first biological DMARD for RA in Japan, to demonstrate the “real-world” data using our registry system. Methods All eligible patients were registered in the Tsurumai Biologics Communication Registry (TBCR), an RA research consortium that consists of Nagoya University Hospital and 12 affiliated institutes. As of September 2011, 2,176 RA patients treated with biologics are registered in this registry system. Four hundred forty seven RA patients previously unexposed to biological DMARDs were treated with infliximab (IFX). Drug retention rates were calculated by Kaplan-Meier method using endpoint of inefficacy or adverse events. Results As baseline characteristics, mean age was 56.6 years, disease duration was 14.9 years, proportion of patients with methotrexate was 99.6%, MTX dose was 7.2 mg/week, proportion of patients with prednisolone (PSL) was 76.1%, PSL dose was 5.2 mg, serum C-reactive protein was 3.8 mg/dL, and DAS28 was 5.7. IFX retention rate was 67.5% at 1 year, 31.0% at 5 years, and 22.5% at 8 years (Fig. 1a). IFX discontinuation rate due to inefficacy was 58.1% (Fig. 1b). Primary inefficacy was seen in 6.9% and secondary inefficacy was seen in 27.1% of patients. Discontinuation rate due to adverse events was 42.7% at 8 years (Fig. 1c). Most frequent adverse events resulted in IFX discontinuation was pulmonary complication (9.8%) including interstitial pneumonia (IP, 2.5%), bacterial pneumonia (4.3%), pulmonary tuberculosis (1.1%), pneumocystis pneumonia (0.7%), and organizing pneumonia (0.4%). The second most frequent was infusion reaction seen in 7.8%. The incidence of malignant neoplasm was seen in 1.8%. Conclusions We observed quite high discontinuation rate due to secondary inefficacy. This is probably dependent on the relatively low MTX dose, because of the Japanese regulation of public health insurance coverage. We are convinced of improved discontinuation rate if only with higher dose of concomitant MTX, which would reduce the production of anti-IFX antibodies resulting in secondary inefficacy and infusion reaction. It was the important data that the most frequent adverse events resulting in discontinuation was pulmonary complications. Putting all our results together, we would suggest that the most suitable patients for IFX treatment, expecting long-tern adherence, would be ones using sufficient dosage of concomitant MTX treatment and do not have baseline comorbidity of pulmonary diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1420

Background Now, predictive factors at baseline for the good outcome of treatment with biologics are very important not to waste time to treatment goal “remission”. Objectives The aims of this study are to clarify the characteristics of the patients enrolled in this observational cohort and to identify the predictive factors at baseline for achievement of the remission in treatment with tocilizumab (TCZ), in daily practice setting with background of limited dose of MTX (5.1) at week 52 were follows: concomitant MTX [OR 2.63 (1.16-6.29)] and less structural damage (Steinbrocker stage I+II)[OR 1.44 (1.55-9.69)]. Interestingly, no significant baseline factors were found in the patients with moderate/low disease activity (DAS28 ≤5.1). However, changes in disease activity and its component showed that patients with moderate/low disease activity and those who did not achieve remission showed no remarkable improvement in patient general assessment (VAS) and tender joint count ([Fig. 1B][1]), compared to patients who had high disease activity and who did not achieve remission ([Fig. 1A][1]) Thus, structural damage could be more influential towards disease activity than inflammation in patients with moderate/low disease activity and those who did not achieve remission. ![Figure 1][2] Figure 1 Conclusions Even low dose of MTX could plays critical roles on RA treatment during TCZ treatment for the patients with high disease activity. The information with background of limited dose of MTX should be important for clinical practice.We should consider structural damage more carefully when the patients with moderate/low disease activity as well as with high disease activity were treated with TCZ to be achieved remission. Disclosure of Interest 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: None declared, K. Funahashi: None declared, S. Asai: None declared, S. Hirabara: None declared, M. Hanabayashi: None declared, Y. Yoshioka: None declared, Y. Yabe: 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 DOI 10.1136/annrheumdis-2014-eular.1710 [1]: #F1 [2]: pending:yes

Background: In Japan, oral tacrolimus (TAC) was approved for the treatment of RA in 2005 and the improvement of symptoms thorough the use concomitant with disease modifying antirheumatic drugs (DMARDs), including MTX has been reported1 2. On the other hand, the efficacy and tolerance of biological agents therapy concomitant with TAC are unknown. Objectives: The objective of this study was to investigate the efficacy and tolerance of biological agents concomitant with TAC in Japanese patients with RA using retention rate analysis. Methods: Total patients (n=2860) who underwent 5 biological agents (etanercept: ETN, adalimumab: ADA, golimumab:GLM, tocilizumab: TCZ, abatacept: ABT) treatment between 2003 and 2017 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group) were enrolled3. In each biologics analysis, patients were divided into three groups: (1) concomitant only MTX (MTX group) (2) concomitant only TAC (TAC group) (3) others (others group). In TAC or MTX group, these drugs were only ones which concomitant with biologics. Kaplan-Meier analysis was used to estimate retention rate in each biologics group. To estimate the tolerance of concomitant biologics with TAC, cumulative hazard function in adverse events rate was performed in each biologics group. In both analyses, hazard ratios (HR) were assessed by Cox proportional hazards modeling adjusted for age, sex, disease duration and previously used biologics. Results: In total 2860 patients, 142 patients (5.0%) administered each biologics concomitant with TAC (ETN: n=47, ADA: n=10 GLM: n=14, TCZ: n=27, ABT: n=49). Baseline characteristics of 142 patients were shown in table 1. Average dosages of TAC at starting were ETN: 2.2±0.7mg ADA: 2.4±1.0mg GLM: 1.9±1.0mg TCZ: 1.7±0.9mg ABT: 1.9±0.9mg. With comparison of retention rate between 3 groups in each biologics under analysis of cox proportional hazard modeling, in ETN and ABT analysis, the retention rate of TAC group was higher than others group (table 2, figure 1). Comparison of incidence of adverse event between 3 group using cumulative hazard function and cox proportional hazard modeling in ETN and ABT analysis. In ETN analysis, incident rate of other group was higher than TAC group. In ABT analysis, there was no significant difference between 3 gruops (figure 2). Conclusion: We suspected that, in ETN and ABT treatment, combination therapy with TAC are subsequent options for treatment to RA patients, especially in whom MTX cannot be administration. References: [1]Kino T, et al. Antibiot. 1987 Sep 40(9): 1256-65 [2]Kondo H, et al. J Rheumatol. 2004 Feb;31(2):243-51 [3]Kojima T, et al. Mod Rheumatol. 2011 Sep 3. Disclosure of Interests: KENYA TERABE: None declared, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Atsushi Kaneko Speakers bureau: Abbvie, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Eli Lily, Mitsubishi-Tanabe, Pfizer, and UCB Japan, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Yuichiro Yabe Speakers bureau: Asahi Kasei, Janssen, and Mitsubishi Tanabe, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama

Background Tocilizumab (TCZ) is the first humanised monoclonal antibody that targets and inhibits the human interleukin-6 receptor. The ACT-RAY study proved the clinical efficacy and safety of adding TCZ to MTX versus switching from MTX to TCZ monotherapy in biologic-naive adult patients with moderate to severe active rheumatoid arthritis (RA). [1]. But the clinical long term outcome is not clear. Objectives To evaluate the continuity and effectiveness of TCZ with/without MTX by using multi-center registry for the treatment of RA with biologics in Japan (Tsurumai Biologics Communication Registry; TBCR) [2]. Methods 302 RA patients treated with TCZ for at least 24 months in Nagoya University Hospital and 12 affiliated institutes (TBCR Study Group) were enrolled in this study.155 cases treated with MTX at the baseline (MTX+ group),147 case did not take MTX at the baseline (MTX- group). Difference in baseline characteristics was summarized in [Table 1][1]. Drug retention rate of both groups was examined using Kaplan-Meier survival analysis. DAS28ESR was compared between these two groups by unpaired t- test at 0, 6, 12, 24 months. The last observation carried forward (LOCF) method was used in each analysis. Results In MTX+ group, 12 cases (7.7%) discontinued TCZ therapy because of inadequate response (IR), 12 cases (7.7%) stopped TCZ infusion because of adverse events (AEs), 8 (5.1%) cases stopped due to other reasons. In MTX- group, 13 cases (8.8%) discontinued TCZ therapy because of IR, 18 cases (12.2%) stopped TCZ infusion because of AEs, 11 (7.5%) cases stopped due to other reasons. DAS28ESR of MTX+ group at 0, 6, 12, 24 months was 5.4, 2.9, 2.7, and 2.7, respectively. That of MTX- group was 5.8, 3.3, 3.3, and 3.4, respectively. Although disease activity based on DAS28ESR was not significantly different between two groups at 0, 6 months, it is significantly different at 12, 24 months (p

Background Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86, and modulating its interaction with CD28. The AMPLE trial demonstrated that clinical efficacy of ABT was equivalent to adalimumab [1]. However, some physicians make assertions that the treatment response of ABT seems to be slower than other class biological DMARDs and we should wait longer periods before deciding whether to continue ABT. Objectives We studied the appropriate periods for deciding to continue or discontinue ABT, by using data from the Japanese multicenter registry system for RA patients using biological DMARDs. Methods All RA patients who underwent ABT treatment for at least 52 weeks (n=254) in Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Registry Study Group [2]) were enrolled in this study. Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels at baseline, 4, 12, 24, and 52 weeks. The last observation carried forward (LOCF) method was used in each analysis. We used a conventional receiver-operating-characteristic (ROC) curve to analyze DAS28 scores at each time point in order to determine the cutoff points that yielded the highest combined sensitivity and specificity with respect to distinguish patients achieved low disease activity (LDA, DAS28-CRP Results In the baseline characteristic data, mean age was 64.5 years, mean disease duration was 11.3 years, and proportion of patients with previous biological DMARDs history was 48.0% and with concomitant MTX usage was 48.8%. We analyzed DAS28 scores at baseline, 4, 12, and 24 weeks. As shown in Fig. 1 left panel, area-under-curve (AUC) was lowest in baseline DAS28 score and highest in 12 and 24 weeks. We chose the shorter time point, 12 weeks, for further study. The cutoff point of DAS28 score at 12 weeks that gave the maximal sensitivity (81%) and specificity (81%) was 3.3. Seventy seven percent of the patients with lower than 3.3 of DAS28-CRP at 12 weeks achieved LDA at 52 weeks (Fig. 1 right panel). Logistic regression analysis identified the previous biological DMARDs history and DAS28-CRP score ( Conclusions According to the difference of AUC score, 4 weeks would be too short and 12 weeks would be long enough to predict low disease activity at 52 weeks in the RA patients treated with ABT. Since we usually decide whether to continue anti-TNF agents at 12 weeks, the treatment response of ABT seemed to be equivalent to that of anti-TNF agents as shown in the AMPLE trial. We would suggest that we can decide to discontinue ABT and switch to other agents if the treatment response is insufficient at 12 weeks. References Arthritis Rheum. 2013;65:28. Mod Rheumatol. 2013;23:904. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2349

Background With the advent of methotrexate and biological disease-modifying antirheumatic drugs, clinical remission has been a realistic goal in rheumatoid arthritis (RA). In 2011 ACR/EULAR Boolean-based definition of remission in RA, patient global assessment (PGA) is often the limiting factor for reaching remission. 1 The main determinants for the PGA are pain, function, and number of swollen joints. 2 Physical function will affair clinical remission. Given the tight correlation between physical function and loss of social and economic opportunities, 3 as well as clinical remission, functional remission is also an important goal. Objectives To clarify the characteristics of Health Assessment Questionnaire (HAQ) and its items from the point of view of disease activity and disease duration of RA. Methods 512 RA patients at Nagoya University Hospital were enrolled in this study. Physical function was assessed using HAQ, disease activity DAS28-CRP, PGA 0-10 visual analog scale. Pearson correlation coefficient, chi square test, and unpaired t-test were used for static analysis. Results Patients were primarily women (81.4%). Mean age was 60.3±14.0 years, disease duration 13.0±10.4 years, HAQ-DI 0.67±0.75, and DAS28-CRP 2.37±1.02. HAQ-DI was getting worse in correlation with disease activity (r=0.452) (Fig. 1), and disease duration (r=0.446) (Fig. 2). In the early stage of RA (duration Considering the questionnaires by, #10 Hygiene, #17 Grip, and #20 Activities had stronger correlation with disease activity. #1 Dressing & Grooming, #5 Eating, and #7 Eating had stronger correlation with disease duration. PGA had a most strong correlation with the HAQ-DI in the components of the DAS28-CRP (r=0.395). Of the patients who are in functional remission (HAQ-DI Conclusions Physical function was associated with disease activity, especially in the early stage. In order to prevent the progression of dysfunction or to achieve functional remission, reducing disease activity is important. Some questionnaires correlated stronger with disease duration rather than disease activity, which suggests that reducing only disease activity is not enough. In addition, HAQ-DI is also associated with PGA. This study suggests that improving HAQ-DI by such as surgery and rehabilitation, leads to not only functional remission but also clinical remission through improving PGA. References Studenic P, Smolen JS, Aletaha D. Near Misses of ACR/EULAR criteria for remission: effects of patient global assessment in Boolean an index-based definitions. Ann Rheum Dis 2012;71:1702-1705 Studenic P, Radnner H, Smolen JS, Aletaha D. Discrepancies between patients and physicians in their perceptions of rheumatoid disease activity. Arthritis Rheum 2012;64:2814-2823 Strand V, Khanna D. The impact of rheumatoid arthritis and treatment on patients9 lifes. Clin Exp Rheumatol 2010;28:S32-40 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2079

Background Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment with Anti-TNFα agents are more clinically effective than the DMARDs that werein use previously, in particular, with their efficacy in suppressing joint destruction having been emphasized. However, most clinical studies on the efficacy of biological agents in suppressing joint destruction in the hands and feet. Therefore, we reported the efficacy of infliximab (IFX) for inhibiting the radiographic progression of RA cervical lesions at ACR2009, EULAR 2010,11 and 12. Objectives To investigatethe efficacy of IFX for inhibiting theradiographic progression of RA cervical lesions over three years. Methods We used IFX for treating 604 Japanese patients with active RA who fulfilled the ACR criteria in 1987. Treatment with IFX was initiated between November 2003 and January 2010; the final study cohort of 45 patients receivedcontinuous IFX treatment for at least 3 years. For evaluation of cervicallesions, theatlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat value weremeasured by plain lateral radiographs in the flexion position, at initiation, 1, 2 and 3year. For evaluation of hand jointlesions, simple X-radiography of both surfaces of the hands was carried out, and joint destruction was evaluated usingthe Sharp/Van der Heijde Score (SHS). Results The mean ADI changed from 3.5 ± 1.8 mm at initiation to 4.0 ± 2.0 mm after 3 years (p 0.5/y) in SHS. In the non-progressive group (n=12) and progressive group (n = 33), the respective changes in cervical lesion parameters in 3 years were as follows:ADI: 0 and 0.76 ± 0.87 mm (p Conclusions IFX treatment can be used to suppress the progression of RA cervical lesions, as well as hand and footjoints lesions. It is possible that response to IFX could be used to predict the progression of RA cervical lesions. 3 year after initiation, the cervical lesion did not progress at all for the patients that a hand joint destruction was prevented as well as the results of one and two year follow-up. Disclosure of Interest : None Declared

Background Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA). Since ABT is often used as second line biologic, it would be important to clarify the impact of the type of previous biologics on ABT efficacy. Additionally, since ABT has also been used as first line biologic in Japan, it is also important to demonstrate the clinical data in biologic naive patients compared to the patients with previous biologic treatment. Objectives We studied whether the history of and the type of previous biologic treatment had any impact on the ABT clinical efficacy in RA patients. Methods All RA patients who underwent ABT treatment for at least 24 weeks (n=111) at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group [2]) were enrolled in this study. Demographic data at baseline and the following parameters of disease activity (tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels during 24 weeks. We compared these clinical data between the patients without previous biologic history (Naive, n=49) and those with previous biologic treatment (Switch All, n=62). The patients with one previous biologic (Switch 2nd, n=33), those with more than two previous biologics (Switch 3rd-, n=29), and Naive group were compared each other. We also compared clinical data between the patients with previous or past tocilizumab treatment (Switch TCZ, n=16), those without TCZ treatment (Switch TNF, n=46), and Naive group. The last observation carried forward (LOCF) method was used in each analysis. Results In the baseline characteristics data, there was no significant difference between Naive and Switch All group, such as mean age (64.8 and 61.9), disease duration (8.7 and 11.9 years), DAS28 (4.4 and 4.6), and CRP (2.0 and 2.5 mg/dL). Although Switch All group showed significant DAS28 decreasing at week 24 compared to week 0, it was significantly higher than that in Naive group (Fig. A-1). As shown in Fig. A-2, DAS28 at week 24 was significantly decreased in both Switch 2nd and Switch 3rd- group compared to week 0, and no significant difference was seen between these two groups. As shown in Fig. A-3, Switch TCZ group did not show statistically significant DAS28 decreasing at week 24 compared to week 0, and it was significantly higher than that in Switch TNF and Naive group. Additionally, the percentage of the patients who achieved low disease activity (DAS28 Conclusions The patients with the history of biologics treatment demonstrated significant improvement in RA disease activity, although the responsiveness to abatacept seemed to be better in the biologic naive patients. However, abatacept demonstrated only inadequate efficacy in the patients with tocilizumab treatment history. Disclosure of Interest N. Takahashi: None Declared, T. Kojima Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, Bristol-Myers Squibb, K. Funahashi: None Declared, D. Kato: None Declared, H. Matsubara: None Declared, Y. Hattori: None Declared, N. Ishiguro Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, Bristol-Myers Squibb

Background In Japan, the aggressive therapy using biologics (Bio) started just 8 years ago. Now, mid, and long-term follow up data for efficacy and safety of the treatment of RA with Bio in real clinical practice should be needed. We set up the multicenter, large cohort study, or registry of RA patients treated using Bio (Tsurumai Biologics Communication Registry; TBCR). Now at 2011, 2073 patients were registered in TBCR. Objectives The aims of this study are to elucidate the trends and safety of Bio treatment for over two years in TBCR, especially in elderly patients, who have relatively high risk associated with the treatment. Methods We collected the data from the patients, who were started treatment with Bio from 2003 to 2008 and registered in TBCR.We surveyed the following information: demographic data,disease activity (DAS28-CRP)at the initiation of biologics, initial Bio, current treatment status (discontinuation of treatment with biologics and its reason).Adverse events were categorized based on ICD-10 classification. In this study, the patients were followed up until August 31, 2010 or until they withdrew from treatment with 1st Bio, whichever came first.Cumulativeincidence rate of those events was determined by Kaplan-Meier method, comparing by age (tertile values) and by starting year of treatment with Bio. Results We analyzed 894 cases. The mean follow up time was 28.5 months. Mean of age and disease duration was 56.3 years old and 11.4 years, respectively. As for changes in baseline characteristics by starting year, patients in young and middle age groups had significant improving in disease activity, and Steinblocker Stage but not those in old age. 124 adverse events were occurred in this study. Most likely events were related to respiratory system (R-AD), 53 cases (43%). About 80% of total AD as well as R-AD were occurred until 24 months. The cumulative incidence rate of R-AD was significant higher in old age group, comparing to young age group (p=0.02). The rate of R-AD in old age group was almost same as that in middle age group after 3 years (Fig 1). In old age group, the cumulative incidence rate of R-AD was improving to same level of younger groups during these 7 years (p=0.04, Fig 2) while there was no significant difference in younger groups (Fig 3 and 4). Conclusions We can treat the patients with RA more aggressively to target “remission” in younger patients, who have relatively lower risk for the treatment with Bio. However, the decision for older age patients in clinical practice is often difficult in point of safety. We clearly showed that incidence rate of most likely serious R-AD significantly decreased especially in older age patients during 7 years-experience. Safety of the Bio treatment can be improved by evidences and experiences during this decade. Further studies should be needed for long term prognosis of RA. Disclosure of Interest T. Kojima Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, K. Funahashi: None Declared, N. Takahashi: None Declared, D. Kato: None Declared, H. Matsubara: None Declared, Y. Hattori: None Declared, N. Ishiguro Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical

Background Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). reatment with biological agents are more clinically effective than the DMARDs that were in use previously, in particular, with their efficacy in suppressing joint destruction having been emphasized. We reported the efficacy of infliximab, anti-tumor necrosis factor antibodies for inhibiting the radiographic progression of RA cervical lesions at ACR2009, EULAR 2010 and 11. However there is still no studies of efficacy of against RA cervical lesions of Tocilizumab(TCZ), anti-interleukin 6 receptor antibody. Therefore, we carried out the present study, which was a prospective investigation in patients receiving TCZ, in order to elucidate the efficacy of TCZ for inhibiting the radiographic progression of RA cervical lesions. Methods We used TCZ for treating 270 Japanese patients with active RA who fulfilled the ACR criteria in 1987.Treatment with TCZ was initiated between July 2008 and December 2010; the final study cohort of 36 patients received ontinuous TCZ treatment for at least 1 year. he TCZ dose was 8 mg/kg. The later doses were administered every 4 weeks up to Week 52. For evaluation of cervical esions, the tlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat value were measured by plain lateral radiographs in the flexion position, at initiation and Week 52. For evaluation of hand joint lesions, simple X-radiography of both surfaces of the hands was carried out, and joint destruction was evaluated using the Sharp/Van der Heijde Score (SHS) at initiation and Week 52. Results The mean ADI changed from 3.3±1.7 mm at initiation to 3.6±1.9 mm after 1 year (p=0.002). The mean SAC changed from 19.0±2.7 to 18.8±2.8 mm over the same period (p=0.003). The mean Ranawat value changed from 5.1±2.4 to 14.9±2.5 mm over the same period (p=0.003). The mean TSS changed from 64.8±53.5 at initiation to 66.4±54.1 after 1 year (p Conclusions TCZ treatment can be used to suppress the progression of RA cervical lesions, as well as hand and foot oints lesions. 1 year after initiation, the cervical lesion did not progress at all for the patients that a hand joint destruction did not progress and the remission patients at Week 52. Disclosure of Interest None Declared

Background In Japan, the treatments for the patients with rheumatoid arthritis using etanercept (ETN) started since 2005. We should carefully treat especially in elderly patients, who have relatively high risk associated with the treatment. Now, mid, and long term follow up data for the efficacy and safety of the treatment of RA with ETN in clinical practice should be needed. Objectives The aims of this study are to investigate the trends and safety of ETN treatment especially in elderly patients. Methods We collected the data from the patients who started ETN treatment as first-biologics since 2005 and registered in the multicenter, large cohort of RA patients (Tsurumai Biologics Communication Registry; TBCR). We surveyed the following information: demographic data, disease activity (DAS28-CRP) at the initiation of ETN, current treatment status (discontinuation of treatment with ETN and its reason). Drug survival rate was determined by Kaplan-Meier method, comparing by age (tertile values), MTX use, and by DAS28-CRP (tertile values) at the initiation of ETN. Cumulative incidence rate of adverse events was determined in the same way. Results We analyzed 683 ETN cases of 1574 cases registered in TBCR until 2010. The mean follow up time was 26.8 months. Mean of age and disease duration was 55.9 years old and 11.0 years, respectively. The rate of concomitant MTX use was 79.6%, 69.5%, 50.0% (young age:≤51, middle age: 52-64, old age: 65≤, respectively). Drug survival rate was significantly lower in old age and no MTX use group (p Conclusions In clinical practice, some elderly patients may not use MTX because of complications. We showed that incidence rate of adverse events was high in those patients. We should treat more carefully the elderly patients who don’t use concomitant MTX. Disclosure of Interest H. Matsubara: None Declared, T. Kojima Speakers Bureau: Abbott Japan, Chugai,Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, N. Takahashi: None Declared, K. Funahashi: None Declared, D. Kato: None Declared, Y. Hattori: None Declared, N. Ishiguro Speakers Bureau: Abbott Japan, Chugai,Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical

Background Bacterial pneumonia is most common respiratory complication in rheumatoid arthritis (RA) patients treated with biologics. There are few reports about detail of pathogenic bacteria or guideline to make a decision on the treatment. Objectives To investigate the outline of bacterial pneumonia in RA patients treated with biologics focusing on pathogens and therapeutic intervention. Methods 1575 RA patients were registered in multi-center registry for the treatment of RA with biologics in Japan (Tsurumai Biologics Communication registry; TBCR) till 2011. 57 cases were interrupted or discontinued the biologics administration due to respiratory infectious complication. We reviewed medical records of those patients and assessed about the pathogens and therapeutic intervention especially in antimicrobial agents retrospectively. Results Excluded the cases of tuberculosis, non tuberculous mycobacteriosis and pneumocystis pneumonia, 31 cases (2.0%) of biologics related bacterial pneumonia (BRP) were investigated. BRP group showed significantly higher age, baseline DAS and longer disease duration (Table 1). The character of BRP was biphasic. 6cases with mild symptoms were successfully treated with oral fluoroquinolones or macrolides without detecting the pathogens in ambulatory care. But 13cases with severe symptoms that’s pathogens were isolated, all patients needed parenteral antimicrobial therapy under hospitalization. Isolated pathogens were higher pathogenic as presented in Table 2. Resistant bacterium such as BLNAR or MRSA were isolated in one case (7.7%) respectively. yogenic or atypical isolates tend to be more often from Community-acquired pneumonia (CAP) to Hospital-acquired pneumonia (HAP) as reported in previous reports, and BRP showed the profile among CAP and Healthcare-associated pneumonia (HCAP) as showed in Table 3. Conclusions The BRP profile of pathogens corresponded with that of HCAP or HAP rather than that of CAP. Classifying criteria for BRP should be established, and if the patient needs intensive care for severe symptoms, therapeutic decision should be made under consideration about resistant bacteria or atypical pathogens as recommended in HCAP or HAP guideline. Disclosure of Interest D. Kato: None Declared, T. Kojima Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Bristol-Myers Squibb, Eisai, Mitsubishi Tanabe, Pharma, Pfizer Japan, Takeda Pharmaceutical, N. Takahashi: None Declared, K. Funahashi: None Declared, H. Matsubara: None Declared, Y. Hattori: None Declared, N. Ishiguro Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Bristol-Myers Squibb, Eisai, Mitsubishi Tanabe, Pharma, Pfizer Japan, Takeda Pharmaceutical