Hisashi Yamanaka

Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Objectives: A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA). Methods: The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly. Results: Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. “Infections” or “respiratory disorders” were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab. Conclusion: This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.

Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients—REACTION 52-week study

Objectives. To evaluate the effectiveness and safety of tocilizumab in RA patients in clinical practice. Methods. We observed 232 consecutive RA patients who began tocilizumab in three rheumatology centres in Japan for 52 weeks. Clinical, radiographic and functional status and safety were evaluated. Results. Mean age of the 232 patients was 59.1 years, mean duration of disease was 12.4 years and average DAS using the 28-joint count (DAS-28) was 5.6. Although 62.8% of the patients had been treated previously with anti-TNF biologics, clinical remission at Week 52 was achieved in 43.7%, radiographic non-progression in 62.8% and functional remission in 26.4%. Retention rate at Week 52 was 71.1%, and the same for those with or without previous anti-TNF treatment. Adverse drug reactions leading to tocilizumab discontinuation were observed in 15.5% of patients, the most frequent adverse drug reaction being pneumonia in eight cases. On multivariate logistic regression analysis, DAS-28, HAQ-disability index (HAQ-DI), concomitant MTX and concomitant glucocorticoids (GCs) were predictive variables for clinical remission at Week 52 of tocilizumab treatment. In particular, HAQ-DI was found to be a predictive variable for remission of all three types—clinical, radiographic and functional—at Week 52 of tocilizumab treatment. Conclusions. In daily clinical practice, tocilizumab exhibited excellent effectiveness in established RA patients, some of whom had failed to respond to previous anti-TNF treatment. Although further detailed safety findings are required, this study provides valuable real-world findings on the management of RA with tocilizumab.

OP0040 Adding Tocilizumab or Switching to Tocilizumab Monotherapy in RA Patients with Inadequate Response to Methotrexate: 24-Week Results from a Randomized Controlled Study (Surprise Study)

Background The efficacy and safety of tocilizumab (TCZ) is established for the treatment of rheumatoid arthritis (RA). However, when TCZ is used to treat RA patients with an inadequate response to methotrexate (MTX), it is not confirmed whether it is better to continue MTX or not. Objectives To compare the efficacy and safety of TCZ monotherapy (SWITCH) and TCZ in combination with methotrexate (ADD-ON) in Japanese RA patients with inadequate response to MTX. Methods The SURPRISE study was a multicentre, prospective, randomized, open-label study. Inclusion criteria were as follows: RA diagnosed by 1987 ACR classification criteria; DAS28-ESR ≥ 3.2; disease duration ≤ 10 years; MTX ≥ 6 mg/week for at least 8 weeks. Patients were randomized to switch to TCZ or to add on TCZ. The primary endpoint was the non-inferiority of combination therapy compared to monotherapy as assessed by the DAS28 remission rate of each group at 24 weeks with a non-inferiority margin of 10% in the per protocol set (PPS). Patients who received ≥1 dose of TCZ were assessed for safety in the full analysis set (FAS). The LOCF method was used to address the missing data on efficacy. Results 233 patients were randomized: 115 to SWITCH and 118 to ADD-ON. At baseline in FAS, mean DAS28 was 5.2±0.1 and 5.1±0.1, disease duration was 4.0±0.3 and 3.8±0.3 years, MTX was 8.4±0.2 and 8.6±0.2, and HAQ-DI was 1.0±0.1 and 1.1±0.1 in the SWITCH and ADD-ON groups, respectively. DAS28 remission at 24 weeks was 59.4% in SWITCH and 71.6% in ADD-ON in PPS (n=106 in SWITCH; n=109 in ADD-ON). The delta between groups in DAS28 remission rate was 12.1 (95% CI; -1.3 – 25.2) supporting the non-inferiority of ADD-ON to SWITCH. Moreover, ADD-ON was superior to SWITCH in terms of DAS28 remission (71.3% vs 57.7%, P=0.0372) in FAS. The rates of ACR20, 50, and 70 response in each group were 66.7%, 53.2%, and 36.0% in SWITCH and 64.3%, 48.7%, and 27.8% in ADD-ON. CDAI, SDAI, and ACR/EULAR remission rates were 27.0%, 30.6%, and 20.7% in SWITCH and 36.5%, 40.0% and 20.0% in ADD-ON. The differences between groups in ACR response rate, CDAI remission, and SDAI remission were not significant. HAQ-DI and EQ-5D were similar in both groups. Incidences of serious adverse events were 9.9% in SWITCH versus 8.7% in ADD-ON; among these were 7 incidences of serious infection (3 pneumonia, 4 other infections). Conclusions In Japanese RA patients with inadequate response to MTX, combination therapy was superior to monotherapy in efficacy as assessed using DAS28 criteria. However, results by other criteria were comparable between groups. In early stage RA, TCZ showed high response, and each of the strategies was useful. Acknowledgements All member of SURPRISE study group. Disclosure of Interest T. Takeuchi Grant/research support from: Abott, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Asahi Kasei, Paid instructor for: Abott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda, Y. Kaneko: None Declared, T. Atsumi Grant/research support from: Kyowa Hakko Kirin, Mitsubishi Tanabe, Chugai, Novartis, Teijin, MSD, Astellas, Sanofi, Takeda, Novo Nordisk, Otsuka, Boehringer Ingelheim, Paid instructor for: Mitsubishi Tanabe, Takeda, Chugai, Pfizer, Y. Tanaka Grant/research support from: Bristol-Myers, MSD, Chugai, Mitsubishi Tanabe, Astellas, Abbott, Eisai, Janssen, Speakers bureau: Mitsubishi Tanabe, Abbott, Eisai, Chugai, Janssen, Santen, Pfizer, Astellas, Daiichi Sankyo, GlaxoSmithKline, Astra Zeneca, Otsuka, Actelion, Eli Lilly, Nippon Kayaku, UCB Japan, Quintiles Transnational, Ono, M. Inoh: None Declared, H. Kobayashi: None Declared, K. Amano Grant/research support from: Chugai, Mitsubishi Tanabe, Astellas, Eisai, Abott, M. Miyata: None Declared, Y. Murakawa Grant/research support from: Teijin, Astellas, Bristol-Myers, Mitsubishi Tanabe, Chugai, Actelion, Takeda, Pfizer, Taisho Toyama, Eisai, Paid instructor for: Santen, Chugai, Kissei, Astellas, Mitsubishi Tanabe, Actelion, Daiichi Sankyo, Takeda, T. Fujii Grant/research support from: Chugai, A. Kawakami Grant/research support from: Chugai, Mitsubishi Tanabe, Pfizer, Takeda, Abott, Eisai, Bristol-Myers, Janssen, Astellas, Santen, Taisho Toyama, Asahi Kasei, Paid instructor for: Chugai, Mitsubishi Tanabe, Pfizer, Takeda, Abott, Eisai, Bristol-Myers, Janssen, Astellas, Santen, Taisho Toyama, Asahi Kasei, H. Yamanaka Grant/research support from: Abbott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, UCB, Paid instructor for: Abbott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, UCB, K. Yamamoto Grant/research support from: ImmunoFuture, Inc, N. Miyasaka Grant/research support from: Abbott, Astellas, Banyu, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Takeda, Teijin, T. Mimori Grant/research support from: Asahi Kasei, Astellas, Bristol-Myers, Chugai, Eisai, Merck, Mitsubishi Tanabe, Pfizer, Santen, Takeda, Speakers bureau: Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe, Pfizer, Santen, Takeda

Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia(®) as Biological Intensive Treatment for RA (ORBIT) study.

Abstract Objective. To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice. Methods. We performed a retrospective study of 137 RA patients who were treated with abatacept for 24 weeks between October 2010 and June 2011 at four rheumatology centers in Japan. Outcomes were compared between biologic-naïve and biologic-experienced patients. Disease activity was assessed using the Simplified Disease Activity Index (SDAI) and the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). Results. The retention rate of abatacept at 24 weeks was 79.6%. SDAI (from 24.6 ± 12.5 to 12.9 ± 11.6) and DAS28-ESR (from 5.2 ± 1.4 to 3.9 ± 1.4) decreased significantly from baseline to Week 24 (both P < 0.001). Remission/low disease activity were achieved in 2.2%/11.2% (SDAI) and in 5.3%/2.3% (DAS28-ESR). The change in SDAI and the remission/low disease activity rates at Week 24 was greater in biologic-naïve patients than in biologic-experienced patients. Structural remission (van der Heijde-modified total Sharp score ≤ 0.5) was achieved by 63.4% of patients. Conclusions. The present results confirm that abatacept is effective in routine clinical practice and support its use as the first-line biologic agent in patients.

Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals: Post Hoc Analysis of Japanese Patients (MELODY Study)

IntroductionThere is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose–response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24xa0weeks in RA patients.MethodsThis analysis used data of the ADA all-case survey in Japan (nxa0=xa07740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0–<4, 4–<6, 6–<8, 8–<xa010, and ≥10xa0mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose.ResultsIn biologic-naïve patients (nxa0=xa01996/3097), LDA/remission rates increased with MTX up to 6–<8xa0mg/week and then plateaued at higher doses (LDA, pxa0=xa00.0440; remission, pxa0=xa00.0422). In biologic-exposed patients (nxa0=xa01101/3097), LDA/remission rates increased with MTX dose (LDA, pxa0=xa00.0009; remission pxa0=xa00.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (pxa0<xa00.05) with increased MTX doses.ConclusionThe appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8xa0mg/week of MTX would be enough for biologic-naïve patients.Trial RegistrationClinicalTrials.gov identifier, NCT01076959.FundingAbbVie and Eisai Co., Ltd.

FRI0177 52-week results of clinical, radiographic and pharmacokinetic assessments: Golimumab, a human anti-TNF monoclonal antibody, administered subcutaneously every four weeks in patients with active rheumatoid arthritis despite methotrexate therapy

Objectives To assess the efficacy and safety of golimumab (GLM) in Japanese patients (pts) with active RA despite MTX therapy. Methods GO-FORTH is a multicenter, randomized, double-blind, placebo (PBO)-controlled study in pts with active RA despite MTX. Pts were randomized to SC PBO, GLM50 mg, or GLM100 mg q4 wks. All pts received MTX 6-8 mg orally/wk. Pts with <20% improvement in SJC/TJC entered early escape (EE) at wk16 in a blinded manner so that PBO→GLM50 mg and GLM50 mg→100 mg. Pts receiving GLM100 mg continued the same dose. Pts who did not enter EE continued initial therapy until wk 24. After wk24, pts who entered EE maintained the wk24 regimen. Pts randomized to PBO who did not enter EE crossed over (CO) to GLM50 mg at wk24. Primary endpoint was the proportion of pts achieving ACR20 at wk14. Secondary variables included ACR20, ACR50, ACR70, DAS28 and HAQ, and changes from BL to wks 24/52 in total vdH-modified Sharp (vdH-S) score. For vdH-S score, treatment grp comparisons at wks 24/52 were based on randomized grps regardless of EE/CO status. Results 261 pts received treatment (88 PBO, 86 GLM50mg, 87 GLM100mg). Both GLM doses were significantly better than PBO in improving signs and symptoms/physical function through wk14 (PBO-controlled period). After wk24, all pts received either GLM50mg or 100mg, and wk 14 efficacy was sustained thorough wk52. At wk52, both of GLM50mg and 100mg yielded significantly less radiographic damage than PBO and pts who received 100mg continued to exhibit less progression through wk52. Significantly more pts treated with GLM 100mg vs PBO had no progression (change in TSS≤0) at wk52. Subgroup analysis (baseline;BL CRP levels ≥1.5 mg/dL vs <1.5 mg/dL) of TSS change from BL was performed in accordance with the report by Emery et al, 2011. Median change in TSS from BL to wk24 was 0.0 in any grp for the pts with BL CRP <1.5 mg/dL. However, for pts with BL CRP ≥1.5 mg/dL, pts in GLM 100mg grp showed less radiographic progression at wk24 than those in pts with PBO and GLM 50mg. The incidence of adverse events (AEs) through wk52 was 89.1% in all GLM-treated pts. Among all AEs, the system organ class with the highest incidence by treatment grp (except for pts who CO GLM50 mg→100 mg) was “Infections and Infestations.” Through wk52, serious AEs occurred in 1.1%, 9.3% and 6.9% of PBO, GLM50mg only and GLM100mg only treated pts, respectively. There were no deaths and no tuberculosis. Conclusions Treatment with GLM50 mg and 100 mg+MTX significantly improved signs/symptoms and inhibited progression of structural damage vs. PBO+MTX. The GLM+MTX safety profile was similar to other anti-TNF agents. Disclosure of Interest None Declared

THU0092 The advantage of early intervention by tocilizumab for rheumatoid arthritis - full analysis of all-case postmarketing surveillance in 7,901 patients in japan

Background Tocilizumab (TCZ), a humanized anti-human interleukin-6 receptor monoclonal antibody, has been approved worldwide for rheumatoid arthritis (RA), and an all-case postmarketing surveillance (PMS) program was conducted in Japan. Objectives The aim of this surveillance is to investigate the safety and effectiveness of TCZ for the treatment of rheumatoid arthritis (RA) in the daily clinical setting. Methods This full analysis report includes 7,901 patients who received TCZ at a dose of 8 mg/kg every 4 weeks, and were observed for 28 weeks. Results Baseline characteristics included: mean age 58.7 years old (≥70 years in 20.7%); mean disease duration 10.4 years (≥10 years in 37.6%); previous TNF inhibitor use in 62.6%, concomitant methotrexate (MTX) use in 55.8% and concomitant glucocorticoid use in 74.0%. The mean DAS28-ESR improved from 5.5 at baseline to 2.9 at week 28 (LOCF method) with TCZ treatment; 47.6% of patients achieved DAS28 remission (DAS28-ESR <2.6), and 15.1% of patients achieved Boolean remission. The DAS28 remission rate and Boolean remission rate were significantly higher in patients whose disease duration was <2 years than in patients whose disease duration was ≥10 years (p<0.0001, χ2 test). Same results were obtained irrespective of the previous use of TNF inhibitor (p<0.0001 for both remission criteria in both TNF inhibitor-naïve and TNF inhibitor-used patients). However, TNF inhibitor-naïve patients showed significantly better response than the TNF inhibitor-used patients (p<0.0001, χ2 test). The incidence rates of all adverse events and serious adverse events (AEs and SAEs) were 43.9% and 9.6%, respectively. The incidence rate of SAEs was significantly lower in patients whose disease duration was <2 years (p<0.0001, χ2 test, vs. ≥10 years). Infections were the most frequent AE (11.1%) and SAE (3.8%). The incidence rates of infections and serious infections were significantly lower in the patients whose disease duration was <2 years (p<0.0001, χ2 test, vs.≥10 years). Similar results were observed when comparing the incidence of serious respiratory infections, which are the most common site-specific infection and serious infection, by disease duration. DAS28 remission (%) Boolean remission (%) Total/by disease duration (years) Total <2 2≤ <10 10≤ Total <2 2≤ <10 10≤ Total patients 47.6 56.1* 50.1 42.4 15.1 22.3* 16.4 10.7 TNF inhibitor naïve 52.5 60.4* 60.7 49.8 21.1† 28.7* 22.6 15.2 TNF inhibitor used 43.2 51.2* 45.7 38.1 11.9 15.7* 13.9 8.2 *P<0.0001, between <2 years and 10≤ years by χ2test, †P<0.0001, between TNF inhibitor naïve and TNF inhibitor used by χ2test. Conclusions Theseresults demonstratedthat treatment with TCZ was effective and well-tolerated in Japanese RA patients in the daily clinical setting, and also suggested that TCZ can be used more effectively and safely in anti-TNF naïve RA patients with shorterdisease duration than in patients with established disease. Disclosure of Interest H. Yamanaka Grant/Research support from: Abbott, Bristol-Myers Squibb, Chugai, Janssen, Eisai, Mitsubishi-Tanabe, Otsuka, Takeda, Pfizer, Consultant for: Abbott, Bristol-Myers Squibb, Chugai, Hoffmann-La Roche, Janssen, Eisai, Mitsubishi-Tanabe, Otsuka, Takeda, Pfizer, M. Harigai Grant/Research support from: Abbott Japan Co. Ltd., Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Consultant for: Abbott Japan Co. Ltd., Chugai Pharmaceutical Company, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corp, S. Inokuma: None Declared, N. Ishiguro Grant/Research support from: Abbott Japan Co. Ltd., Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Speakers Bureau: Chugai, Eisai, Astellas, Mitsubishi-Tanabe, Takeda, J. Ryu: None Declared, S. Takei: None Declared, T. Takeuchi Consultant for: Abbott Immunology Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Chugai, Astellas, Mitsubishi-Tanabe, Pfizer, Takeda, Y. Tanaka Consultant for: Abbott Immunology Pharmaceuticals, Chugai, Eisai, Astellas, Mitsubishi-Tanabe, Takeda, Y. Sano Employee of: Chugai, T. Koike Consultant for: Abbott Immunology Pharmaceuticals, Bristol-Myers Squibb,Astellas, Otsuka, Speakers Bureau: Abbott Immunology Pharmaceuticals, Chugai, Eisai, Mitsubishi-Tanabe, Takeda, Pfizer

Four cases of HLA-A*26(+)/B*51(−) intestinal Behçet’s disease without abdominal symptoms

Abstract Behçet’s disease (BD) is a systemic inflammatory disorder and involvement of the bowel leads to a poor prognosis due to perforation of intestinal ulcers and penetration of ulceration into surrounding organs. We describe the clinical features of 4 Japanese BD patients (1 male) with intestinal lesions detected by colonoscopy, and the 4 patients had no abdominal complaints at their first admission to our hospital from 2003 to 2005. Case 1 was a 74-year-old woman, Case 2 was a 25-year-old woman, Case 3 was a 32-year-old woman, and Case 4 was a 32-year-old man. The characteristics of BD which they all had in common were recurrent oral aphthous ulcers, erythema nodosum, acneiform eruption, genital ulcers, polyarthritis and gastrointestinal lesions without abdominal complaints. None of these patients were positive for HLA-B*51, but all of them had HLA-A*26. Our findings suggest that screening colonoscopy is important for diagnosing intestinal BD in order to achieve a good prognosis.

FRI0210 Real-world hawk study: long-term safety and effectiveness of adalimumab with higher-dose methotrexate in japanese patients with early rheumatoid arthritis

Background TNF inhibitors are first-line biologic therapy used in combination with MTX for treatment of RA. However, in Japan, limited real-world data exist on this combination with relatively higher doses of MTX (>8 to ≤16 mg/week). Objectives The HAWK study was designed to assess real-world, long-term safety and effectiveness of the TNF inhibitor ADA with MTX (≥12 mg/week) in Japan. Week 52 results are presented. Methods This multicenter, prospective, observational study, enrolled biologic-naïve, early (≤2 years) RA patients with DAS28-CRP>3.2 despite MTX therapy for ≥3 months. Eligible patients received ADA + MTX (≥12 mg/week at beginning of ADA) for 104 weeks. Primary endpoint was DAS28-CRP <2.6 at week 52. Secondary endpoints included CDAI, SDAI, HAQ-DI and inhibition of structural joint damage using the mTSS. ADRs and dosage of ADA and MTX were recorded. Results As of April 15, 2016, 346 patients were enrolled (safety set 301; effectiveness set 293). Effectiveness set comprised 73% women; mean (±SD) age, 54.3 (13.9) years; duration of RA, 12.1 (6.2) months; MTX dosage, 13.4 (1.8) mg/week; DAS28-CRP, 4.5 (0.9); and mTSS, 7.7 (10.0) at baseline. At week 52, DAS28-CRP <2.6 and low disease activity (<3.2) were achieved in 77% and 92% patients, respectively. Remission rates in CDAI (≤2.8), SDAI (≤3.3), and HAQ-DI (≤0.5) were 49%, 51%, and 82%, respectively. Although average MTX dosage was decreased (≤2 mg/week), unchanged, and increased (≥2 mg/week) from baseline in 19.6%, 78.9%, and 1.4% patients over 52 weeks, respectively, there was no significant difference in disease activity improvement across these MTX dosage groups at week 52 (p=0.350). Structural remission rate at week 52 was 86% (ΔmTSS ≤0.5) (Figure). A total 110 ADRs occurred in 80 (26.6%) patients, 23 were serious in 21 (7.0%) patients (Table). All (N=301) Serious (N=301) ADR u2003Total 80 26.6% 21 7.0% ADRs by SOC u2003Infections and infestations 29 9.6% 9 3.0% u2003Investigations 16 5.3% 1 0.3% u2003Respiratory, thoracic and mediastinal disorders 13 4.3% 3 1.0% u2003Hepatobiliary disorders 9 3.0% 0 ADRs of particular interest u2003Tuberculosis 0 0 u2003Pneumocystis jirovecii pneumonia 4 1.3% 4 1.3% u2003Pneumonia bacterial* 6 2.0% 4 1.3% u2003Herpes zoster 4 1.3% 0 u2003Malignancy (1) 4 1.3% 4 1.3% u2003Interstitial lung disease 2 0.7% 2 0.7% u2003Sepsis 0 0 u2003Pancytopenia 0 0 u2003Reactivation of hepatitis B 0 0 *Pneumonia, Pneumonia bacterial, Pneumonia pneumococcal, Pneumonia legionella, Pneumonia streptococcal. (1) Colon cancer, diffuse large B-cell lymphoma, ovarian cancer metastatic, lung neoplasm malignant. Conclusions Results show that ADA with MTX (≥12 mg/week at the beginning) displayed a consistent safety profile and was effective with a DAS28-CRP remission rate of 77% in routine clinical practice. The ADR rate of 26% was similar to a previous, short-term (28 weeks) postmarketing surveillance report (1). References Koike et al. Mod Rheumatol 2014; 24:390–8. Acknowledgements This study (NCT01736189) was funded by AbbVie GK and Eisai Co., Ltd. AbbVie participated in the collection, analysis, and interpretation of the data, and in the drafting, review, and approval of the abstract. AbbVie GK and Eisai Co., Ltd. provided funding to EPS Corporation for data analysis and to Cactus Communications for editorial assistance. Disclosure of Interest Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, Consultant for: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, GlaxoSmithKline, T. Mimori Grant/research support from: Acterion, Ayumi, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi Tanabe, Speakers bureau: Chugai, Mitsubishi Tanabe, H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer, UCB. Nippon Kayaku, YL biologics, Bayer, Bristol-Meyers, Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer, UCB, Nippon Kayaku, YL biologics, Bayer, Bristol-Meyers, R. Nakajima Employee of: AbbVie GK, K. Morita Employee of: AbbVie GK, J. Kimura Employee of: AbbVie GK, T. Takeuchi Grant/research support from: AbbVie, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Asahi Kasei Medical, Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda

AB0668 A Pilot Study of the Eicosapentaenoic Acid/Arachidonic Acid (EPA/AA) Ratio Level of Japanese Patients with Behçet's Disease

Background Kürkçüoğlu (1) reported for the first time for the efficacy of eicosapentaenoic acid (EPA) to the patients of Behçets disease (BD). In Japan, the anti-inflammatory efficacy of EPA to the patients with BD was reported (2, 3). Recently, low level of EPA/AA ratio protecting the events of coronary artery disease was reported in Japan (4, 5). The level of EPA/AA ratio in the patients with BD was not elucidated in the daily clinical practice. Objectives To investigated the relationships between states of BD and the level of EPA/AA ratio of the patients with BD in daily medical practice. Methods We analyzed the levels of EPA/AA ratio in 25 patients with BD. The examinations of fatty acid fractions were performed in a daily general blood survey. We keep the regulation of medical insurance for the whole nation. The disease activity was shown with the score of patients global assessment VAS (PtGA), in this study. Our hypothesis was that the level of EPA/AA ratio is decreased in the vascular-BD patients as for an anti-inflammation and anti-vasculitis. Results We analyzed 25 patients with BD who visited our clinic in resent 2 years from 2012 to 2013. The characteristics of 25 patients with BD were as shown below: oral lesions were shown in all 25 patients with BD, skin lesions in 24, genital ulcers in 19, ocular lesions in 10, arthritis in 19, intestinal lesions in 11, neural lesions in 3 and vascular lesions in 5. The total 3 times were analyzed in this study, thus the characteristics of our total patients were below: oral lesion 75, skin lesions 71, genital ulcer 61, ocular lesions 26, arthritis 59, intestinal lesions 40, neural lesions 9 and vascular 19, and the average of EPA/AA ratio was 0.41 (SD =0.30). We participated this 75 into 3 categories: 19 were over the normal EPA/AA ratio (0.11 – 0.5), 54 were within the normal ratio and 2 were under the normal ratio. Also the mean EPA/AA ratio (SD) were 0.84 (0.29), 0.27 (0.097) and 0.077 (0.0011), respectively. Our hypostasis was confirmed, and the 2 patients of under the standard value of EPA/AA/ratio were same one patients who was an intestinal-BD patient and had sever digestive symptoms at the time. The decrease in-take was the cause of the decreasing EPA/AA ratio. Conclusions The level of EPA/AA ratio was not related the activities in the Japanese vascular-BD patients. References Kürkçüoğlu, N. and Tandoğdu, R: Brit J Dermatol. 121: 667-8, 1989. Annual report of the Behçets Disease Research Committee of Japan. 185-7, 1992. Annual report of the Behçets Disease Research Committee of Japan. 160-2, 1993. Yokoyama M, et al. Lancet 2007: 369. 1090-8. Ninomiya T, et al. Atherosclerosis. 2013; 231. 261-7. Disclosure of Interest None declared