Y. Yabe

Tokyo Kosei Nenkin Hospital, Edo, Tokyo, Japan

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Publications (37)237.8 Total impact

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    ABSTRACT: 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.
    No preview · Article · Feb 2016 · Clinical Rheumatology
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    ABSTRACT: This study aimed to identify predictive factors for achieving low disease activity (LDA) in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT). Patients who were registered in the multicenter observational Tsurumai Biologics Communication Registry (TBCR) were enrolled in this study. Predictive factors for LDA achievement at each time point were determined by univariate and multivariate logistic regression analyses. The cutoffs of 28-point count Disease Activity Score (DAS28)-C-reactive protein (CRP) and ΔDAS28-CRP from baseline up to 24 weeks for LDA achievement at 52 weeks were explored using receiver operating characteristic (ROC) curves. Of 2771 RA patients registered until 2013, 76 with moderate or high disease activity were selected. Twenty-six percent of the patients achieved LDA. Multivariate analysis confirmed that DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks were independent factors for LDA achievement at 52 weeks [odds ratio (OR) 0.26, 95 % confident interval (CI) (0.12-0.56), OR 0.25, 95 % CI (0.11-0.57), respectively]. The best cutoff values of DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks for LDA at 52 weeks were 3.9 (sensitivity 0.85, specificity 0.78) and -0.97 (sensitivity 0.70, specificity 0.70), respectively. Seventy-one percent of patients who achieved both of these cutoff values at 12 weeks achieved LDA at 52 weeks. Our findings suggest that the clinical course up to 12 weeks is important for predicting long-term outcomes when switching from TNFis to ABT.
    No preview · Article · Dec 2015 · Clinical Rheumatology
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    ABSTRACT: 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-naïve 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-naïve patients could achieve LDA at 52 weeks significantly more than in biologics-switching patients (56.0% vs 23.0%, p<0.001, Fig.1). Both naïve and switching patients who achieved LDA had no significant differences in background and improving to 12 weeks while the improving between 12-24weeks was less in bio-switching patients (Fig.2.). In biologics-switching patients, multivariate analysis revealed that baseline variables could not predict LDA achievement at 12 and 52 weeks at all, but DAS28-CRP at 12 weeks was an independent factor (OR: 0.20, p<0.001). DAS28-CRP at 0w-24w had significant association with LDA at 52 weeks in bio-naïve patients while DAS28-CRP at 0w in bio-switching patients did not (Fig.3). In bio-switching patients, the best cut-off of DAS28-CRP at 12w was 3.9 (sensitivity=0.83, specificity=0.81, positive predictive value: 0.56). In those patients with DAS28-CRP at 12w <3.9, the best cut-off of improving in DAS28-CRP from baseline to 12 weeks was 0.74 (sensitivity: 0.79, specificity: 0.60). We could predict LDA accurately (positive predictive value: 0.71) by these two indices in biologics switching patients. 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.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: 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<4.0 at 12 weeks was an independent factor (OR: 22.9) for LDA achievement at 52 weeks. Previous etanercept was independent negative factor for LDA achievement at 12w (OR: 0.15), referred to infliximab. Patients who were switched from ETN to ABT could need longer time (more than 24 weeks) for improving than those switched from IFX. Background with low dose or no MTX could cause the production of anti-drug antibody, especially, in IFX and ADA. There is a possibility that switching to ABT could have more effective in bio-switching patients with anti-drug antibody. 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.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment 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 (IFX), anti-tumor necrosis factor antibodies for suppressing the radiographic progression of RA cervical lesions at ACR2009, EULAR2010, 11, 12, 13 and 14. However there is still few studies of efficacy of against RA cervical lesions of Tocilizumab (TCZ), anti-interleukin 6 receptor antibody. Objectives To evaluate the efficacy of TCZ for suppressing the radiographic progression of RA cervical lesions comparison with IFX for 2 years. Methods We used TCZ and IFX for treating each 270 and 604 Japanese patients with active RA who fulfilled the ACR criteria in 1987 from Tsurumai Biologics Communication Registry (TBCR). The final study cohort of each 21 and 88 patients received continuous TCZ and IFX treatment for at least 2 years. The TCZ dose was 8 mg/kg. The later doses were administered every 4 weeks up. For evaluation of cervical lesions, the atlanto-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 Year 1,2. Results In the patients receiving TCZ (n=21) and IFX (n=88), the number of female were each 14 (67%) and 75 (85%) cases (p=0.062). The mean age was 58.3±10.6 and 53.9±12.9 years old (p=0.289); disease duration was 7.3±6.9 and 10.7±9.2 years (p=0.125); the number of biologics naïve patient were 4 (19%) and 85 (97%) cases (p<0.001) and the number of receiving methotrexate (MTX) was 16 (76%) and 88 (100%) cases (p<0.001). Clinical findings related to RA were as follows; CRP 4.2±3.1 and 3.1±2.8 mg/dl (p=0.073); ESR 56.0±27.0 and 49.9±29.1mm/h (p=0.367); MMP3 476±347 and 337±309ng/ml (p=0.049); DAS28 5.59±0.74 and 5.47±1.25 (p=0.642); ADI 2.8±1.8 and 3.6±1.9mm (p=0.031); SAC 19.3±2.9 and 18.1±2.7mm (p=0.060) and Ranawat value 15.0±1.7 and 14.5±2.2mm (p=0.518). The respective changes in cervical lesion parameters after 1 year were as follows: ADI: 0.19±0.51and 0.22±0.44 mm (p=0.579); SAC: −0.19±0.40 and −0.16±0.40 mm (p=0.647); and Ranawat value: −0.14±0.36 and −0.15±0.36 mm (p=0.955). The respective changes in cervical lesion parameters after 2 years were as follows: ADI: 0.29±0.56 and 0.35±0.59 mm (p=0.609); SAC: −0.24±0.44 and −0.27±0.60 mm (p=0.958); and Ranawat value: −0.24±0.44 and −0.26±0.47 mm (p=0.890). The numbers of patients who did not showed progression in ADI, SAC, Ranewat value and all three parameters were each 16 (76%) and 62 (70%) cases (p=0.789); 16 (76%) and 68 (77%) cases (p=0.910) and 16 (76%) and 66 (75%) cases (p=0.910) after 2 years. Also the number who was able to suppress progression in all three parameters were each 15 cases (71%) receiving TCZ and 58 cases (66%) receiving IFX (p=0.797). Conclusions This study suggested that TCZ treatment can be used to suppress the progression of RA cervical lesions as well as IFX treatment. Disclosure of Interest Y. Kanayama: None declared, T. Kojima Speakers bureau: Abbott Japan Co. Ltd.; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Corporation; Pfizer Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; and Bristol-Myers Squibb Co. Ltd., Y. Hirano Speakers bureau: Abbott Japan Co. Ltd.; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Corporation; Pfizer Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; and Bristol-Myers Squibb Co. Ltd., Y. Yabe: None declared, N. Takahashi Speakers bureau: Abbott Japan Co. Ltd.; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Corporation; Pfizer Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; and Bristol-Myers Squibb Co. Ltd., S. Hirabara: None declared, N. Ishiguro Speakers bureau: Abbott Japan Co. Ltd.; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Corporation; Pfizer Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; and Bristol-Myers Squibb Co. Ltd.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, was approved in 2008 for use in clinical practice in Japan. The efficacy of tocilizumab in treating rheumatoid arthritis (RA) has been demonstrated in several clinical trials as well as in clinical practice. Given the high efficacy and safety, few patients switch from tocilizumab to other drugs, and limited studies have been reported in this regard. Controversy exists as to whether tumor necrosis factor inhibitors (TNFi) or abatacept should be selected when switching from tocilizumab. Objectives The aim of this study was to compare the clinical efficacy of two classes of biologics, TNFi and abatacept, after switching from tocilizumab therapy. Methods We performed a retrospective multicenter study of 40 RA patients who underwent 52-week biologic therapy after switching from tocilizumab therapy (Tsurumai Biologic Communication Registry). Patients were divided into two groups based on the biologic they switched to: TNFi (n=18) and abatacept (n=22). Changes in clinical parameters were examined at 0, 24, and 52 weeks after the switch: tender joint count (TJC) and swollen joint count (SJC) on 28 joints, general health on a visual analog scale (GH-VAS), and serum C-reactive protein (CRP) levels. Disease activity was evaluated at each time point using the 28-joint disease activity score with CRP (DAS28-CRP), as well as the clinical disease activity index (CDAI), which included data from the above-mentioned disease parameters. Results Patients at baseline had a mean age of 60.3 years, mean disease duration of 12.1 years, and mean DAS28-CRP of 5.1. There was no significant difference between the two classes of drugs at baseline, except in disease durations and oral steroid use (%). Retention rates for TNFi and abatacept treatment at 52 weeks were 78.6% and 80.1%, respectively (Figure 1). Discontinuation due to all unfavorable causes did not significantly differ between the two in hazard ratio-based evaluations (Table 1). DAS28-CRP levels were lower with TNFi compared to abatacept at 24 weeks (TNFi, 3.52; abatacept, 4.12, p=0.033), but no difference was found at 52 weeks (TNFi, 3.55; abatacept, 3.94, p=0.135) (Figure 2). Percentages of subsequent low disease activity of CDAI for TNFi and abatacept were 46.2%, and 22.2%, respectively. Conclusions This study is the first to compare the clinical efficacy of two different classes of biologics (TNFi and abatacept) after switching from tocilizumab using a multicenter registry system. Our results show that TNFi and abatacept are both effective, with no significant differences. When switching from tocilizumab, the characteristics of each drug should be considered to make an appropriate choice for each patient. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: 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 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.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.
    No preview · Article · May 2015 · Rheumatology International
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    ABSTRACT: This study aimed 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%) patients received concomitant MTX at a median (IQR) dose of 8 (6-8) mg/week. A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P<0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio: 0.36, 95% confidence interval: 0.20 to 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. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    No preview · Article · Apr 2015
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    ABSTRACT: Our study aimed to evaluate the longterm efficacy and safety of abatacept (ABA), and to explore factors that increase its longterm efficacy in patients with rheumatoid arthritis (RA) treated in routine clinical practice. There were 231 participants with RA treated with ABA who were prospectively registered in a Japanese multicenter registry. They were followed up for at least 52 weeks. Mean age of the patients was 64.3 years, mean disease duration was 12.1 years, mean 28-joint Disease Activity Score (DAS28)-C-reactive protein was 4.49, and 48.5% of patients were concomitantly treated with methotrexate (MTX). Overall retention rate of ABA was 77.1% at 52 weeks; 14.8% of patients discontinued because of inadequate response and 3.5% because of adverse events. The proportion of patients achieving DAS28-defined low disease activity (LDA) significantly increased from baseline to 52 weeks (7.3% to 43.8%, p < 0.01); 40.9% of patients who did not achieve LDA at 24 weeks had more than 1 categorical improvement in DAS28-defined disease activity at 52 weeks. Multivariate logistic regression revealed concomitant MTX use to be an independent predictor of the categorical improvement in DAS28-defined disease activity from 24 to 52 weeks (adjusted OR 3.124, p = 0.010). In routine clinical practice, ABA demonstrated satisfactory clinical efficacy and safety in patients with established RA for 52 weeks. The clinical efficacy of ABA increased with time even after 24 weeks, and this was strongly influenced by concomitant MTX use. Our study provides valuable real-world findings on the longterm management of RA with ABA.
    No preview · Article · Apr 2015 · The Journal of Rheumatology
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    ABSTRACT: Objectives: Tacrolimus (TAC) and abatacept (ABT) inhibit T-cells via different mechanisms and, in combination, may be effective against rheumatoid arthritis. However, they may also disrupt normal immune functions. We compared the efficacy and safety of ABT administered to patients in combination with TAC, methotrexate (MTX), or other drugs. Methods: This was a retrospective multicenter study conducted to compare the efficacy and safety of ABT in 211 patients: the drug was administered together with TAC (ABT+ TAC group; 22 patients), MTX (ABT+ MTX group; 102 patients), or patients treated without concomitant MTX or TAC (ABT mono group; 87 patients). The disease activity, treatment continuation rate, and reason for discontinuation of treatment were investigated. Results: The retention rate at Week 24 was similar in the three groups. There were no cases of discontinuation related to the appearance of adverse events in the ABT+ TAC group. At Week 24, according to the European League Against Rheumatism response criteria, the "good" response rates were 33.3%, 13.4%, and 13.4% in the ABT+ TAC, ABT+ MTX, and ABT mono groups, respectively. Statistically significant decreases in various disease activity scores/indices were observed in all the groups as early as Week 4. Conclusions: Although the sample size was small, the results of this retrospective study suggest that the ABT+ TAC combination therapy has at least comparable safety and efficacy to those of the ABT+ MTX combination, and that it can thus be a useful option for patients who cannot take MTX.
    No preview · Article · Mar 2015 · Modern Rheumatology
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    ABSTRACT: Objective: Only a few studies have assessed predictive factors for the long-term efficacy of abatacept. This study aimed to provide clinical evidence of an adequate observational period for predicting low disease activity (LDA) achievement at 52 weeks in RA patients treated with abatacept. Methods: Participants were all patients registered in a Japanese multicentre registry who were treated with abatacept and had at least 52 weeks of follow-up (n = 254). Results: Areas under the receiver operating characteristic curves for the 28-joint count with CRP (DAS28-CRP) at each time point for LDA achievement at 52 weeks were: 0.686 (cut-off score: 4.6) at baseline, 0.780 (3.8) at 4 weeks, 0.875 (3.3) at 12 weeks, and 0.900 (3.0) at 24 weeks. Although patients with a DAS28-CRP score < 3.0 at 24 weeks had the highest proportion of LDA achievement at 52 weeks (79.3%), the proportion for those with a score < 3.3 at 12 weeks was comparable (77.2%, P = 0.697). Proportions were significantly lower in patients with a score < 3.8 at 4 weeks or < 4.6 at baseline. Multivariate logistic regression demonstrated that a DAS28 score of < 3.3 at 12 weeks was an independent strong predictor for LDA at 52 weeks (adjusted odds ratio: 15.2, P < 0.001). Conclusion: Twelve weeks is an adequate observational period to judge the long-term clinical efficacy of abatacept, and is about as early as the period for assessing TNF blockade therapy.
    No preview · Article · Oct 2014 · Rheumatology (Oxford, England)
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    ABSTRACT: Objectives. The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX. Methods. A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents. Results. Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model. Conclusions. Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.
    No preview · Article · Sep 2014
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    ABSTRACT: Objectives: The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX. Methods: A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents. Results: Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model. Conclusions: Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.
    No preview · Article · Sep 2014 · Modern Rheumatology
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    ABSTRACT: Objective: The purpose of this study was to identify the effects of concomitant use of MTX and baseline characteristics for remission in the treatment of RA with tocilizumab (TCZ) in daily clinical practice. Methods: A total of 240 RA patients who received TCZ were selected from the multicentre Tsurumai Biologics Communication Registry. Predictive baseline factors for remission [28-item DAS (DAS28) < 2.6] at 52 weeks were determined by logistic regression analysis. To confirm whether the associations varied by the level of baseline disease activity, we also assessed the model including the interaction term (each baseline variable × DAS28). Results: In total, 49.3% of the study participants used MTX with TCZ. Even after controlling for the baseline DAS28, shorter disease duration (≤3 year) [odds ratio (OR) 3.58 (95% CI 1.81, 7.07)], less structural damage [Steinbroker stage ≤II, OR 2.33 (95% CI 1.32, 4.12)] and concomitant prednisolone use [OR 0.38 (95% CI 0.21, 0.68)] showed significant predictive values for remission. Concomitant MTX use failed to show a significant association with remission, whereas a significant interaction was observed among concomitant MTX use × DAS28 (P = 0.006). In patients with high baseline disease activity (DAS28 > 5.1), concomitant MTX use was associated with increased odds for remission [adjusted OR for all baseline variables 2.54 (95% CI 1.11, 5.83)], while no association was indicated between them in patients with low to moderate baseline disease activity (DAS28 ≤ 5.1). Conclusion: Concomitant MTX use is an important component of TCZ treatment for RA patients with high disease activity.
    No preview · Article · Aug 2014 · Rheumatology (Oxford, England)
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    ABSTRACT: 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.
    No preview · Article · Jul 2014 · The Journal of Rheumatology
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    ABSTRACT: The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab, and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy. Patients at baseline had a mean age of 58.7 years, mean disease duration of 9.8 years, and mean clinical disease activity index (CDAI) of 22.4. There was no significant difference between the three drugs, except in rheumatoid factor positivity. Retention rates for abatacept, tocilizumab, and etanercept treatment at 52 weeks were 72.0, 89.5 and 84.6 %, respectively. The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs. Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations. Our results show that patients treated with abatacept, tocilizumab, and etanercept achieved a high response rate with no significant differences in drug retention rates and clinical efficacy. These drugs represent good therapeutic options for patients with RA who are refractory to anti-TNF monoclonal antibody therapy.
    Full-text · Article · Jun 2014 · Clinical Rheumatology
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    ABSTRACT: Background Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment with biological agents are clinically effective in particular, with their efficacy in suppressing joint destruction having been emphasized. However there is still no studies of efficacy of against RA cervical lesions of Tocilizumab (TCZ), anti-interleukin 6 receptor antibody. Objectives To evaluate the efficacy of TCZ for suppressing 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. The final study cohort of 52 patients received continuous TCZ treatment for at least 1 year. For evaluation of cervical lesions, ADI, SAC and the Ranawat value were measured by plain lateral radiographs, at initiation and Week 52. Results The group of patients included 11 males and 41 females. The mean age was 53.4±12.9 years old; disease duration was 10.8±9.7 years; and the number of receiving methotrexate (MTX) was 37 (71%). Clinical findings related to RA were as follows; CRP, 3.7±2.6mg/dL; ESR, 56.1±27.0mm/h; DAS28 5.72±1.07; and CDAI, 24.7±12.7; ADI, 3.4±1.9mm; SAC, 18.9±2.7mm; Ranawat value, 14.9±2.7mm and TSS, 67.3±56.8. The numbers of patients who did not showed progression in ADI, SAC, Ranewat value and all three parameters were 37 (73%), 37 (73%), 39 (76%) and 36 (69%). In the naive (n=9) and switch patients (n=43), the respective changes in cervical lesion parameters in 1 year were as follows: ADI: 0.22±0.44 and 0.30±0.51 mm (p=0.707); SAC: −0.33±0.50 and −0.26±0.44 mm (p=0.637); and Ranawat value: −0.22±0.44 and −0.23±0.43 mm (p=0.947). In the patients of combination MTX (n=37) and non-combination MTX (n=15), the respective changes in cervical lesion parameters in 1 year were as follows: ADI: 0.32±0.53 and 0.20±0.41 mm (p=0.455); SAC: −0.24±0.44 and −0.33±0.49 mm (p=0.511); and Ranawat value: −0.22±0.42 and −0.27±0.46 mm (p=0.698). In the DAS remission (n=32) and non-remission patients (n=20), the respective changes in cervical lesion parameters in 1 year were as follows: ADI: 0.13±0.34 and 0.55±0.61 mm (p=0.003); SAC: −0.13±0.34 and −0.50±0.51 mm (p=0.003); and Ranawat value: −0.19±0.40 and −0.30±0.47 mm (p=0.354). On the other hand in the CDAI remission (n=14) and non-remission patients (n=38), the respective changes in cervical lesion parameters in 1 year were as follows: ADI: 0 and 0.40±0.55 mm (p=0.009); SAC: 0 and −0.37±0.49 mm (p=0.009); and Ranawat value: 0 and −0.32±0.47 mm (p=0.018). In the non-progressive (ΔTSS≤0, n=18) and progressive patients (ΔTSS >0, n=34), the respective changes in cervical lesion parameters in 1 year were as follows: ADI: 0 and 0.44±0.56 mm (p=0.002); SAC: 0 and −0.41±0.50 mm (p=0.002); and Ranawat value: 0 and −0.35±0.49 mm (p=0.004). Conclusions TCZ treatment can be used to suppress the progression of RA cervical lesions regardless of naïve or switch and with or without MTX. 1 year after initiation, the cervical lesion did not progress at all for the patients that a hand joint destruction did not progress and who achieved remission of the CDAI criteria at Week 52. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3741
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Ankylosing spondylitis (AS) is a systemic inflammatory disease that affects the physical capacity of patients globally. Exercises are recommended to the management of patients with AS, although the benefits of specific exercise programs are not yet well defined. Objectives To evaluate the effectiveness of a progressive muscle strengthening program using a Swiss ball in improving functional capacity, muscle strength, disease activity, mobility and quality of life of patients with AS. Methods Sixty patients were randomized to intervention group (IG) or to control group (CG), with 30 patients in each group. Eight exercises were done by GI with free weights on a Swiss ball, 2 times per week for 16 weeks. Loads were reassessed and increased every 4 weeks. The GC continued drug therapy without any exercise, on a waiting list. The evaluations were performed by a blinded evaluator immediately before randomization and at 4, 8, 12 and 16 weeks after initiation of the study. Functional capacity were evaluated using the BASFI (Bath Ankylosing Spondylitis Functional The Index), HAQ-S (Health Assessment Questionnaire for Spondyloarthropathies), the 6-minute walk test and the Time Up and Go test. Muscle strength was assessed by the 1-repetition maximum (1 RM) test. Disease activity was measured by BASDAI (The Bath Ankylosing Spondylitis Disease Activity Index) and by dosage of ESR and C-reactive protein. The BASMI (The Bath Ankylosing Spondylitis Metrologyl Index) was used to assess spinal mobility and the SF-36 questionnaire to assess quality of life. Patients were also evaluated by Likert scale for satisfaction. In addition, the amount of analgesic and non-steroidal anti-inflammatory used was controlled. Results The groups were homogeneous at baseline for clinical and demographic characteristics. There was a statistically significant difference between the two groups in the improvement of strength in IG compared to the CG for the muscles used in the exercises: abdominal (p = 0.003), rowing exercises (p = 0.02), squat (p = 0.01), triceps (p = 0.021) and reverse fly (p = 0.02). The IG also improved the 6-minute walk test (p = 0.005) at week 16 compared with the CG. We also found a statistically significant difference between groups in the Likert scale at all times (p <0.001) with IG showing greater treatment satisfaction. We found no differences between groups in other variables and there was no worsening of disease activity in IG. Conclusions The progressive muscle strengthening using a Swiss ball is effective in improving muscle strength and walking performance in patients with AS. The exercise program has shown good tolerance assessed by patient satisfaction without deleterious effects on disease activity. The trial was registered in clinicaltrials.gov (NCT01351311). References References Disclosure of Interest None Declared
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: 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 (<8mg/week). Methods This study included 240 RA patients who received TCZ in the multicenter study group (Tsurumai Biologics Communication Registry; TBCR, 2176 cases treated with biologics were registered until 2011). We explored the differences in baseline characteristics by concomitant use of MTX and by achievement of remission. We also determined the predictive baseline factors for DAS28-ESR remission at week 52 using multivariate logistic regression analysis. Cases in which TCZ therapy was discontinued before 52 weeks were not excluded but rather categorized as “non-responder” for treatment (non-responder imputation). Results Baseline characteristics: mean (SD); Age 57.9 (13.2) ys, Disease duration 10.2 (8.3) ys, DAS28-ESR 5.6 (1.3), concomitant PSL 67.5%, concomitant MTX 48.8%, mean dose of 7.6 mg/week (In Japan, dose of MTX is limited up to 8mg/week until 2011), previous use of biologics 67.9%. Remission rate (DAS28-ESR) at 52 weeks was 42.9%. We found that DAS28-ESR was significantly lower in patients with concomitant MTX. In the high disease activity group, patients who achieved remission had significantly higher rates of concomitant MTX, less progressive Steinbrocker stages, but not the proportion of patients with previous use of biologics while, in patients with the moderate/low disease activity group (DAS28-ESR ≤5.1), we found no significant differences in baseline characteristics. The multivariable logistic regression analysis showed predictive factors for remission in patients with high disease activity (DAS28 >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), compared to patients who had high disease activity and who did not achieve remission (Fig. 1A) 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. 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
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases