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Background There is no report investigating predictive factors for MRI erosion change in treatment of rheumatoid arthritis (RA) with abatacept (ABT), because very little data are available on the efficacy of ABT assessed by MRI. Objectives The aim of this study is to examine the efficacy of ABT in patients with RA assessed by MRI and identify factors associated with change of bone erosion score. Methods Thirty-five RA patients were included in this prospective study. MRI of bilateral hands and conventional radiographs (CR) of bilateral hands and feet were performed at baseline and month 12 of treatment with intravenous ABT. MRI images were scored for synovitis, osteitis and bone erosion according to the Rheumatoid Arthritis MRI Scoring System. CR images were assessed according to the van der Heijde modified total Sharp score. Results Thirty-one patients completed this study. Mean Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline were 23.4±12.0 and 1.1±0.6 respectively. At the group level, mean MRI synovitis and osteitis scores showed statistically significant reductions through 12 months of treatment with ABT (from 17.1±7.0 to 11.4±6.2 (p Conclusions This study demonstrated ABT has a strong inhibitory effect on joint damage reducing synovitis and osteitis and not progressing bone erosion in RA patients. Over 10% patients showed repair of bone erosion assessed by MRI, which resulted in functional remission. SDAI response rate at month 1 could be a predictive factor for repair of bone erosion. Disclosure of Interest Y. Kukida Grant/research support from: Bristol-Myers Squibb, A. Kasahara: None declared, T. Seno: None declared, T. Inoue: None declared, N. Kamio: None declared, R. Sagawa: None declared, T. Kida: None declared, A. Nakabayashi: None declared, H. Nagahara: None declared, A. Yamamoto: None declared, S. Morita: None declared, H. Ito: None declared, M. Kohno: None declared, Y. Kawahito Grant/research support from: Bristol-Myers Squibb

Background Tocilizumab, anti-IL-6 receptor monoclonal antibody, is widely used for patients with rheumatoid arthritis. IL-6 is essential for production of C-reactive protein (CRP). Tocilizumab fully inhibit the production of CRP. Therefore, we have difficulty in objective assessment of infection and disease activity because the level of CRP is suppressed under tocilizumab therapy. The development of new biomarker alternative to CRP is needed for daily practice. Objectives To discover new biomarkers alternative to CRP under tocilizumab therapy for rheumatoid arthritis. Methods We registered patients with rheumatoid arthritis treated with tocilizumab. We collected serum samples from those patients at baseline, 4 weeks after the first tocilizumab administration when patient9s CRP level is almost normal, and 1 year later. And we measured CRP, ESR and clinical disease activity index (CDAI) score.Serum peptidomic analysis was conducted by newly-established one-step direct transfer technology (BLOTCHIP-MS analysis), a rapid quantitative technology for peptidomic analysis. All sample measurements were repeated four times. Statistical analyses of MS spectral data were conducted using ClinProTools version 2.2 (Bruker Daltonics). Results We registered 14 patients and their background is shown in Table 1. The levels of CRP were 1.16±0.99 mg/dl at baseline, 0.02±0.01 mg/dl at 4 weeks and 0.01±0.01mg/dl at 1 year, respectively. Their CDAI score were 22±9.2 at baseline, 15±8.9 at 4 weeks and 3±2.6 at 1 year, respectively. CRP titer decreased to almost normal level at 4 weeks regardless whether CDAI score did not fully decrease. We detect 6 biomarkers, named as PRSJ01 to PRSJ06, by the peptidomic analysis (Table 2). The AUC of diagnostic value of these markers is from 0.742 to 0.858. For example, the level of PRSJ06 significantly decreased 4 weeks (Wilcoxon singed-rank test, p=0.02) and 1 year (Wilcoxon singed-rank test, p=0.003) after first tocilizumab administration (Figure 1). and it was inversely-correlated with CDAI score. Conclusions We detect new disease activity biomarkers alternative to CRP under tocilizumab therapy for rheumatoid arthritis. It is useful for exact evaluation of disease activity and infection during tocilizumab therapy. Disclosure of Interest None declared

Background Multitarget therapy for lupus nephritis which was reported by Bao et al. 1 is hopeful treatment option for refractory systemic lupus erythematosus (SLE). However, there are few studies about multitarget therapy with combination of prednisolone (PSL), purine synthesis inhibitor and calcineurin inhibitor for SLE. Objectives The aim of this study is to evaluate efficacy and safety of multitarget therapy with combination of PSL, mizoribine (MZR) and tacrolimus (TAC) as induction or add-on therapy for refractory SLE with or without lupus nephritis. Methods We retrospectively studied 26 SLE patients treated with multitarget therapy in our department from April 2009 to December 2013. The mean age was 44.5 years old and 23 patients were female. They were divided into two groups; (A) 10 patients who were initially treated with this therapy as induction, and (B) 16 patients who were additionally treated with this therapy due to minor flares or difficulty in reducing PSL dose. We evaluated efficacy and safety of this combination strategy as (A) induction therapy and (B) add-on therapy respectively. Results (A) Five of 10 patients had lupus nephritis (2 were class IV and 3 were class IV+V). Three of 10 stopped this therapy due to severe adverse events within 12 months. Other 2 patients stopped this therapy due to preparation for pregnancy. Among nephritis patients, complete renal response rate at 6 months was 75%. The mean SLE disease activity index (SLEDAI) was reduced from 25 at baseline to 7.5 at 6 months. In all non-nephritis patients, their symptoms or blood examination data were improved. The mean SLEDAI was reduced from 14.4 at baseline to 2.4 at 6 months. (B) Five of 16 patients had lupus nephritis. One patient stopped this therapy due to preparation for pregnancy. The mean PSL dose was reduced from 14.8mg/day at baseline to 9.2mg/day at 12 months. The mean SLEDAI was reduced from 6.5 at baseline to 2.7 at 12 months. In all 26 patients, adverse events were 28 cases in the observation period. Most of these were mild infections. Three severe adverse events were observed. These were hypertrophic cardiomyopathy due to interaction of TAC and clarithromycin, nocardial soft tissue abscess and cryptococcal meningitis. All three patients who experienced severe adverse events were over 65 years old. Conclusions The combination use of PSL, MZR and TAC is effective as induction therapy and as add-on therapy for refractory SLE regardless of having lupus nephritis. However, elderly patients tend to suffer from sever adverse events. References Bao H et al: Successful treatment of class V+IV lupus nephritis with multitarget therapy, J Am Soc Nephrol 19; 2001-2010, 2008 Disclosure of Interest Y. Kukida Grant/research support: Astellas Pharma Inc. Asahi Kasei Pharma Corp., T. Kida: None declared, T. Inoue: None declared, Y. Isoda: None declared, T. Sagawa: None declared, R. Ishigaki: None declared, A. Kasahara: None declared, A. Nakabayashi: None declared, K. Fujioka: None declared, H. Nagahara: None declared, W. Fujii: None declared, K. Murakami: None declared, T. Seno: None declared, A. Yamamoto Grant/research support: Astellas Pharma Inc. Asahi Kasei Pharma Corp., M. Kohno Grant/research support: Astellas Pharma Inc. Asahi Kasei Pharma Corp., Y. Kawahito Grant/research support: Astellas Pharma Inc. Asahi Kasei Pharma Corp. DOI 10.1136/annrheumdis-2014-eular.3186

Background It is well known that synovial fluid pH is decreased in rheumatoid arthritis (RA) patients (1), but the meaning and mechanism remain unclear. Objectives We investigate the correlation between synovial fluid pH and the disease activity of RA. We reveal the mechanism by which synovial fluid pH is regulated and explore the novel therapeutic strategy of RA by applying this mechanism. Methods We measured the values of pH and the concentration of L-lactate in synovial fluid of RA patients. Next, we investigated the expression of ion transporters regulating intracellular and extracellular pH in RA synovial fibroblasts (RASFs) obtained from the inflamed joints using quantitative RT-PCR and Western Blotting. Finally, we suppressed the ion transporter expression by small interfering RNA (siRNA) against the ion transporter increased in RASFs, and analyzed their viability and proliferative capacity of RASFs. Results Synovial fluid pH was decreased as the disease activity score (DAS)-28 CRP increased in RA patients (graph A, n=17, r = -0.81, p