Y. Yabe

AB0377 Differences in Baseline Predictive Factors for Remission at 52 Weeks by Concomitant MTX Use during Tocilizumab Treatment Using Propensity Score Matched Groups

Background In the treatment of rheumatoid arthritis, concomitant use of methotrexate (MTX) should be a critical factor for decision of treatment now. Tocilizumab, IL-6 receptor antibody has been reported to have good efficacy even without concomitant MTX in clinical trials and observational study. However, there is an important clinical question that concomitant MTX use could have any impacts on predictive factors of achievement of good clinical goal. Objectives To explore the differences in predictive factor for achievement of remission by concomitant MTX use during TCZ treatment. In observational study, it is important to match background of the patients for comparison. We used propensity score matching, which is useful statistical tool for comparison in clinical practice. Methods This study included 240 RA patients who received TCZ (concomitant MTX use: MTX(+) 117: no use: MTX(−) 123) in the multicenter observational cohort (Tsurumai Biologics Communication Registry; TBCR, 2827cases treated with biologics were registered until 2014). We prepared matched groups by concomitant MTX use using propensity score (matched factors, age, sex, previous biologics use, glucocorticoid use, Steinbrocker stage and class, disease duration, DAS28 at baseline). We determined the baseline predictive factors for remission (DAS28) at week 52 by the matched groups using multivariate logistic regression analysis. Especially, association of DAS28 at baseline to achievement of remission was compared using area under the curve (AUC) of ROC curve. Results Sixty-nine patients were matched between groups. Baseline characteristics were shown in Table 1. Rate of remission was 55.2% in MTX(+) group and 44.8% in MTX(−) group (p=0.39). Independent predictive factors at baseline for remission were disease duration [OR:0.90, 95%CI (0.83–0.97)] in MTX(+) group while DAS [OR:0.49, 95%CI (0.29–0.83)] in MTX(−) group based on multivariate analysis. We also showed significant difference in association of DAS at baseline to remission between groups using AUC of ROC curve (AUC 0.59 vs 0.73, Fig. 1). Interestingly, after matching baseline characteristics, achievement of remission in MTX(−) group depended on disease activity at baseline while that in MTX(+) group did not. The cut-off value of DAS28 at baseline for achievement of remission was 4.87 (sensitivity 0.61, specificity 0.84) in MTX(−) group. Conclusions There is significant difference in baseline predictive factors for good clinical results by concomitant MTX use during TCZ treatment. The results should be taken into consideration to predict clinical response in clinical practice. Disclosure of Interest T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, AbbVie, Bristol-Myers Squibb, and Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma and Chugai Pharma., S. Asai: None declared, 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 Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., Y. Yabe: None declared, Y. Hirano Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, and Bristol-Myers Squibb., Y. Kanayama: None declared, A. Kaneko Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, Chugai Pharma, Abbott, Bristol-Myers Squibb, UCB, Janssen, and Pfizer, T. Takemoto: None declared, N. Asai: None declared, T. Watanabe: None declared, K. Funahashi: None declared, M. Hayashi: 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, AbbVie, 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, AbbVie, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan

FRI0254 Efficacy of tocilizumab for suppressing radiographic progression of cervical lesions in patients with rheumatoid arthritis comparison with methotrexate treatment; two years of follow-up ∼a multicenter registry study ∼

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 IFX comparison with methotrexate (MTX). Objectives To evaluate the efficacy of IFX for suppressing the radiographic progression of RA cervical lesions comparison with MTX for 2 years. Methods We used MTX or MTX+IFX for treating Japanese patients with active RA who fulfilled the ACR criteria in 1987. The final study cohort of each 40 and 88 patients received continuous MTX and IFX treatment for at least 2 years. MTX was used in all patients receiving IFX. 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 MTX (n=40) and IFX (n=88), the number of female were each 33 (83%) and 75 (85%) cases (p=0.794). The mean age was 62.5 ± 10.7 and 53.9 ± 12.9 years old (p<0.001); disease duration was 9.3 ± 10.0 and 10.7 ± 9.2 years (p=0.127) and the mean dose of MTX was 7.3 ± 2.4 and 7.8 ± 2.1 mg/w (p=0.414). Clinical findings related to RA were as follows; CRP 1.3± 2.0 and 3.1± 2.8 mg/dl (p<0.001); ESR 28.1 ± 21.1 and 49.9 ± 29.1mm/h (p<0.001); MMP3 170 ± 303 and 337 ± 309ng/ml (p<0.001); DAS28 4.07 ± 1.42 and 5.47 ± 1.25 (p<0.001); ADI 2.6 ± 1.6 and 3.6 ± 1.9mm (p=0.001); SAC 20.2 ± 2.7 and 18.1 ± 2.7mm (p<0.001) and Ranawat value 16.0 ± 1.5 and 14.5 ± 2.2mm (p<0.001). The respective changes in cervical lesion parameters after 1 year were as follows: ADI: 0.25 ± 0.44 and 0.22 ± 0.44 mm (p=0.591); SAC: −0.18 ± 0.39 and −0.16 ± 0.40 mm (p=0.716); and Ranawat value: −0.13 ± 0.34 and −0.15 ± 0.36 mm (p=0.733). The respective changes in cervical lesion parameters after 2 years were as follows: ADI: 0.53 ± 0.72 and 0.35 ± 0.59 mm (p=0.193); SAC: −0.48 ± 0.64 and −0.27 ± 0.60 mm (p=0.038); and Ranawat value: −0.35 ± 0.58 and −0.26 ± 0.47 mm (p=0.486) (Fig. 1). The numbers of patients who did not showed progression in ADI, SAC and Ranawat value were each 24 (60%) and 62 (70%) cases (p=0.310); 24 (60%) and 67 (76%) cases (p=0.058) and 28 (70%) and 66 (75%) cases (p=0.666) after 2 years. Also the number who was able to suppress progression in all three parameters were each 24 cases (60%) receiving MTX and 58 cases (66%) receiving IFX (p=0.555) after 2 years (Fig. 2). Conclusions This study suggested that IFX treatment can be used to suppress the progression of RA cervical lesions more than MTX treatment. Disclosure of Interest Y. Kanayama: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, AbbVie,Bristol-Myers Squibb, and Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma and Chugai Pharma., Y. Hirano Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, and Bristol-Myers Squibb., 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 Pharmaceutical Co. Ltd,Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., Y. Yabe: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, TaishoToyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, AbbVie, 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, AbbVie, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.

AB0480 Clinical Efficacy of TNF Inhibitors and Abatacept in Japanese Rheumatoid Arthritis Patients Switching from Tocilizumab

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 Nishimoto N, et al. Ann Rheum Dis. 2009;68(10):1580-4. Kojima T, et al. Mod Rheumatol. 2012;22(3):370-5. Yamanaka H, et al. Mod Rheumatol. 2011;21(2):122-33. Disclosure of Interest None declared

AB0466 The Outcome of Tocilizumab Treatment with Achievement of Glucocorticoids Withdrawal Against Rheumatoid Arthritis for 24 Months from TBC Registry

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.

AB0487 Efficacy of Tocilizumab for Suppressing Radiographic Progression of Cervical Lesions in Patients with Rheumatoid Arthritis Comparison with Infliximab; Two Years of Follow-Up – a Multicenter Registry Study

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.

AB0485 Predictive Factors for Achievement of Low Disease Activity or Remission at 52 Weeks in Switching from TNF Inhibitors to Abatacept with Background of low Dose or no Methotrexate: A Multicenter Observational Cohort Study in 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<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.

FRI0332 Considering the Maintenance Treatment with TOCILIZUMAB for Rheumatoid Arthritis, We HAD Better Treat in Combination with Mtx. the Report of 2Years Multi-Center Clinical Practice

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-naïve 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. 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<0.01) (Fig. 1). The continuation of both groups was not significantly different by the Kaplan-Meier method ((Log-rank test; p=0.70) (Fig. 2). The proportion of low disease activity and remission based on DAS28ESR was 65.0% in MTX+ group and 41.3% in MTX- group at 24 months (Fig. 3). Conclusions Although the continuity of TCZ therapy is not significantly different with/without MTX, the clinical response of TCZ therapy is significantly different with/without MTX in 2 years results. Considering the maintenance treatment with TCZ for RA, we had better treat TCZ in combination with MTX. References Ann Rheum Dis. 2013 Jan;72(1):43-50. Mod Rheumatol. 2012 Jun;22(3):339-45. 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: None declared, M. Hanabayashi: None declared, S. Hirabara: None declared, S. Asai: 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.3231

SAT0251 Three Biological DMARDS of Different Classes Exhibit Equivalent Efficacy in Rheumatoid Arthritis Patients with Inadequate Response to Anti-TNF Monoclonal Antibodies

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

SAT0063 Importance of Concomitant Methotrexate with TOCILIZUMAB and Assessment of Structual Damage for Achieving Better Clinical Outcomes for Rheumatoid Arthritis Patients with High Disease Activity: an Observational Cohort Study

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. 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

THU0129 The Effectiveness of Biologic Agents Concomitant with Tacrolimus in Rheumatoid Arthritis

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=1541) who underwent 4 biological agents (etanercept: ETN, adalimumab: ADA, tocilizumab: TCZ, abatacept: ABT) treatment between 2003 and 2011 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) monotherary (mono group). In TAC or MTX group, these drugs were only ones which concomitant with biologics. Patients who underwent biologics combined with other DMARDs were excluded. 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 was performed in each biologics group. Results In total 1541 patients, 91 patients (5.9%) administered each biologics concomitant with TAC (ETN: n=38, 101.0 patient-years (PY) ADA: n=13, 12.8 PY TCZ: n=24, 40.8 PY ABT: n=17, 16.2 PY). Average dosages of TAC at starting were ETN: 2.1±0.7mg ADA: 1.5±1.0mg TCZ: 2.2±0.9mg ABT: 2.4±0.9mg. With comparison of retention rate in each biologics concomitant with TAC, ADA was significantly lower rate than other 3 biologics (Fig. 1). Each biologics agents number was ETN (MTX: n=641, 1473.0 PY mono: n=194, 469.1PY), ADA (MTX: n=641, 1473.0 PY mono: n=34, 35.2PY), TCZ (MTX: n=181, 247.5 PY mono: n=85, 120.0PY), ABT (MTX: n=85, 89.6 PY mono: n=38, 35.1PY). In only ETN analysis, the retention rate of TAC group was higher than mono group (Fig. 2). In ADA, that of MTX group was higher than TAC and mono group. There was no difference of comparison that of other 2 biologics analysis. Comparison of incidence of adverse event between TAC and mono group using cumulative hazard function in each biologics analysis, in only ETN analysis incident rate of mono group was higher than TAC group and there was no difference in other 3 biologics analysis (Fig. 3). Conclusions We suspected that combination therapy ETN and TAC are subsequent options for treatment to RA patient, especially in whom MTX cannot be administration. References Kino T, et al. Antibiot. 1987 Sep 40(9): 1256-65 Kondo H, et al. J Rheumatol. 2004 Feb;31(2):243-51 Kojima T, et al. Mod Rheumatol. 2011 Sep 3. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3634