Ryoko Sakai

Tokyo Medical and Dental University, Edo, Tokyo, Japan

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Publications (17)81.1 Total impact

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    ABSTRACT: Objective: To reveal any association between rheumatoid arthritis (RA) and cardiovascular comorbidities using a Japanese health insurance database. Method: This population-based cross-sectional study was conducted using health insurance data provided by the Japan Medical Data Center Co., Ltd. We identified 2762 RA subjects having RA diagnostic codes (ICD10 codes; M05, M060, M062-63, M068-069) with at least two physician visits more than two months apart between June 2011 and May 2012 (RA group, n = 2762). We selected age- (±5 years), sex-, and study period-matched non-RA subjects (non-RA group, n = 27,620). We compared the prevalence of cardiovascular and related comorbidities (ischemic heart diseases [IHD], cerebral infarction, hypertension [HT], dyslipidemia [DL], and diabetes mellitus [DM]) between these groups and investigated the association between RA and cardiovascular comorbidities using a conditional logistic regression analysis. Results: The prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group. Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 2.0 [1.5-2.5] and 3.1 [2.2-4.2] respectively, after adjusting for HT, DL, and DM. Conclusions: This study revealed for the first time in the Japanese population that RA was significantly associated with cardiovascular comorbidities.
    No preview · Article · Dec 2015 · Modern Rheumatology
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    ABSTRACT: The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice. This prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry. We assessed types and incidence rates (IRs) of serious adverse events (SAEs) and serious infections (SIs) during the first year of treatment. Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis. Patients in the TCZ group had longer disease duration (P <0.001), higher disease activity (P = 0.019) and more frequently used concomitant corticosteroids (P <0.001) than those in the TNFI group. The crude IR (/100 PY) of SIs [TCZ 10.68 vs. TNFI 3.03; IR ratio (95% confidence interval [CI]), 3.53 (1.52 to 8.18)], but not SAEs [21.36 vs. 14.72; 1.45 (0.94 to 2.25)], was significantly higher in the TCZ group compared with the TNFI group. However, after adjusting for covariates using the Cox regression hazard analysis, treatment with TCZ was not associated with higher risk for SAEs [hazard ratio (HR) 1.28, 95% CI 0.75 to 2.19] or SIs (HR 2.23, 95% CI 0.93 to 5.37). The adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs, indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice.
    Full-text · Article · Dec 2015 · Arthritis research & therapy
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    Preview · Article · Sep 2015 · The Journal of Rheumatology
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    ABSTRACT: Background In the treat-to-target strategy (T2T)1, simplified disease activity index (SDAI) has been proposed as one of measures to define remission2. Predictive ability of SDAI remission for functional and structural outcomes was shown by data from clinical trials, but has not been proven in a T2T implementing cohort. Objectives To examine if achieving SDAI remission is a predictor of good functional and structural outcomes in a T2T implementing cohort. Methods The T2T Epidemiological Study is a multi-centre, prospective cohort study, in which RA patients with moderate to high disease activity were enrolled and treated with T2T for 72 weeks. The disease activity was assessed every 12 weeks and the treatment was adjusted accordingly. Primary outcomes were HAQ and ΔmTSS at week 72. Multivariate logistic regression analysis was used to examine association between SDAI remission at week 24 and the two primary outcomes. Missing data were imputed using the multiple imputation method. Statistical significance levels were adjusted for multiple comparison using False Discovery Rate and BH methods. Results Of total 318 enrolled patients, 244 patients followed up for 72 weeks were analysed. Patient characteristics were as follows: female, 77%; mean age, 61; mean disease duration, 57 months. At week 24, 33% achieved SDAI remission. At week 72, 50% achieved SDAI remission, 61% achieved HAQ remission (≤0.5) and 73% showed ΔmTSS<smallest detectable change (SDC). Factors [odds ratio (95%CI)] significantly associated with HAQ remission at week 72 were Steinbrocker's stage I [2.35 (1.23-4.46), p=0.009], baseline HAQ [0.30 (0.19-0.47), p=2.4x10-7], absence of history of joint replacement related to RA [9.90 (1.57-62.5), p=0.015] and SDAI remission at week 24 [3.24 (1.57-6.71), p=0.0015]. Factors associated with ΔmTSS<SDC were Steinbrocker's stage I [2.82 (1.40-5.65), p=0.0037], serum MMP-3 level at week 24 [0.998 (0.996-1.000), p=0.035] and SDAI remission at week 24 [3.21 (1.46-7.02), p=0.0036]. Conclusions SDAI remission at week 24 is a significant predictor of good functional and structural outcomes at week 72 in the T2T implementing cohort. References Acknowledgements We all thank all health care professionals and patients who participated in this study. Disclosure of Interest F. Hirano: None declared, W. Yokoyama: None declared, H. Yamazaki Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., Sekisui Medical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and UCB Japan, K. Amano Grant/research support from: Astellas, Chugai, Pfizer, Tanabe-Mitsubishi, Consultant for: Zenyaku Kogyo, Paid instructor for: Chugai, Pfizer, Santen, Tanabe-Mitsubishi, Speakers bureau: AbbVie, Actellion, Astellas, Bristol-Myers-Squibb, Chugai, Diichi-Sankyo, Eisai, Pfizer, Tanabe-Mitsubishi, Y. Kaneko Consultant for: Abbvie, Paid instructor for: Eisai Pharmaceutical, Chugai Pharmaceutical, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen, UCB, A. Kawakami Grant/research support from: Abbvie GK, Eisai Co., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Janssen Pharmaceutical K. K., Takeda Pharmaceutical Company, Astellas Pharma Inc., Santen Pharmaceutical Co., Bristol-Myers Squibb, ONO Pharmaceutical Co., Chugai Pharmaceutical Co., Taisho Toyama Pharmaceutical Co., Speakers bureau: Abbvie GK, Eisai Co., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Janssen Pharmaceutical K. K., Takeda Pharmaceutical Company, Astellas Pharma Inc., Santen Pharmaceutical Co., Bristol-Myers Squibb, ONO Pharmaceutical Co., Chugai Pharmaceutical Co., Taisho Toyama Pharmaceutical Co., T. Matsui: None declared, R. Sakai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., Sekisui Medical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and UCB Japan, R. Koike: None declared, N. Miyasaka Grant/research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Dainihon-Sumitomo Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd, Consultant for: Abbott Japan Co., Ltd., Bristol Myers Squibb, Janssen Pharmaceutical KK, and Otsuka Pharmaceutical Co. Ltd., M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, Consultant for: Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical KK, Teijin Pharma Ltd.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients receiving immunosuppressive treatment for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. During the observation period, 32 patients died (4.2%) and 66 patients were lost to followup (8.6%). Patients with PI (n = 61, 8%) had a significantly worse accumulated survival rate than patients without (p < 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age ≥ 65 years (HR 3.87, 95% CI 2.22-6.74), ≥ 20 pack-years of smoking (2.63, 1.37-5.04), higher serum creatinine level (1.21, 1.05-1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35-5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95% CI 1.36-17.01 per 1.0 mg/dl increase; 2.57, 1.28-5.16 if ≥ 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.
    No preview · Article · Feb 2015 · The Journal of Rheumatology
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    ABSTRACT: Objective: Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP. Methods: A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model. Results: A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42 patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates. Conclusion: Careful consideration of the benefit-risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.
    No preview · Article · Dec 2014 · Modern Rheumatology
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    ABSTRACT: To investigate changes in the risk for serious infections (SIs) over time in Japanese rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors (TNFIs). This prospective cohort study included Japanese RA patients who began treatment with a TNFI from 2005 to 2007 (2005 group, n = 716, 634.2 patient years [PY]) and from 2008 to 2011 (2008 group, n = 352, 270.1 PY) at the time or after their enrollment in the registry of Japanese RA patients on biologics for long-term safety (REAL) database. Patients were observed for 12 months or until discontinuation of their initial TNFI in the REAL database. Drug discontinuation reasons and retention rates were analyzed. Incidence rates of serious adverse events (SAEs) were calculated with 95 % confidence intervals (CIs). The Cox proportional hazard model was applied to estimate the risk for SIs. The retention rate in the 2008 group was significantly lower than the 2005 group (p
    Preview · Article · Dec 2014 · Rheumatology International
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    ABSTRACT: Background The high prevalence or risk of comorbidities in patients with rheumatoid arthritis (RA) has been reported1,2. It is essential for rheumatologists to manage comorbidities appropriately since they influence on prognosis of RA patients3. However, there are no reports investigating the prevalence of comorbidities such as cardiovascular diseases in RA patients using large population-based data in Asia. Objectives To compare the prevalence of comorbidities between RA cases and non-RA cases and reveal the association between RA and comorbidities using Japanese health insurance database. Methods This cross-sectional, population-based study was conducted using reimbursement data provided by the Japan Medical Data Center Co., Ltd. We defined individuals as RA cases if they had at least two physician visits more than two months apart with RA diagnostic codes4 (ICD10 codes; M05, M060, M062, M063, M068, and M069) between June 2011 and May 2012 (RA group, n=2,762). The month that a patient had one of the RA diagnostic codes for the first time was defined as the index month. Among individuals who did not meet above criteria, we selected age- (±5 years), gender-, and observation term-matched non-RA cases at 1:10 ratio (RA cases: non-RA cases) (non-RA group, n=27,620). Patients who had the following ICD 10 codes (ischemic heart diseases (IHD) [I20-22, I25], cerebral infarction [I63], osteoporosis [M80-81]) and were prescribed for the comorbidities at least one time within 6 months before or after the index month were deemed as having comorbidities. We compared the prevalence of comorbidities between the two groups by chi-square test and investigated the association between RA and comorbidities using logistic regression analysis. Results The mean age of this population was 50.4 for the RA group and 50.0 for the non-RA group, and 74.1% were female in the both groups. In the RA group, 9.4% of cases were prescribed biological DMARD, 29.1% methotrexate (MTX), 22.8% synthetic DMARDs other than MTX, and 31.6% oral corticosteroids in the index month. Prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group (RA vs. non-RA, IHD [5.0% vs. 1.4%], cerebral infarction [2.5% vs. 0.6%], osteoporosis [19.9% vs. 1.2%]). Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 1.8 [1.5-2.3] and 2.0 [1.5-2.7], respectively, after adjusting for hypertension, hyperlipidemia, diabetes mellitus, and use of celecoxib, and for osteoporosis 9.4 [7.8-11.3] after adjusting for use of oral corticosteroids ≥5mg/day). Conclusions This study revealed that RA was significantly associated with investigated comorbidities using health insurance database for the first time in Asia. References Acknowledgements This work was supported by the research grant from the Ministry of Health, Labour, and Welfare, Japan. Disclosure of Interest R. Sakai Employee of: Tokyo Medical and Dental University (TMDU) receives unrestricted research grants from Abbvie Japan Co. Ltd., Astellas Pharma Inc., Bristol Meyears Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., and UCB Japan for Department of Pharmacovigilance with which TMDU pays salary for RS., F. Hirano: None declared, M. Kihara: None declared, W. Yokoyama: None declared, H. Yamazaki Employee of: Tokyo Medical and Dental University (TMDU) receives unrestricted research grants from Abbvie Japan Co. Ltd., Astellas Pharma Inc., Bristol Meyears Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., and UCB Japan for Department of Pharmacovigilance with which TMDU pays salary for HY., R. Koike: None declared, N. Miyasaka Grant/research support: NM has received research grants from Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Dainihon-Sumitomo Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd and received Consulting fee or honorarium from Abbott Japan Co., Ltd., Bristol Myers Squibb, Janssen Pharmaceutical KK, and Otsuka Pharmaceutical Co. Ltd., M. Harigai Grant/research support: MH has also received research grants from Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd and Sekisui Medical Co., Ltd., Employee of: Tokyo Medical and Dental University (TMDU) receives unrestricted research grants from Abbvie Japan Co. Ltd., Astellas Pharma Inc., Bristol Meyears Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., and UCB Japan for Department of Pharmacovigilance with which TMDU pays salary for MH. DOI 10.1136/annrheumdis-2014-eular.1296
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Pulmonary comorbidity (PC) is a clinically important complication in patients with rheumatoid arthritis (RA) because PC has been recognized as one of the prognostic factors for RA1-3 and often prevents patients from receiving aggressive treatments for RA. Furthermore, Japanese may be more susceptible to development of PC than other ethnic groups4. However, a difference in risk factors for serious infections (SIs) between patients with and without PC has not been thoroughly studied yet. Objectives To compare risk factors for SIs between patients with and without PC using the Registry of Japanese RA patients for Long-term safety (REAL) database. Methods This study included Japanese RA patients who started biologics or nonbiological DMARDs at the enrollment in the REAL database. Case report forms were filed by attending physicians every 6 months up to 5 years for each patient in the REAL. Observation period of this study started at the enrollment in the REAL and was censored after 2 years. We analyzed types and incidence rates of SIs. Analysis included 360 patients with PC [PC group, 589 patient-years] and 1,384 patients without PC (non-PC group, 2,325 patient-years). PC included interstitial pneumonia (193), obstructive pulmonary diseases (30), bronchiectasis (20),and other pulmonary diseases. To identify risk factors and hazard ratio (HR) for SIs in each group, Cox proportional-hazard regression analysis was applied. Results At baseline, patients were older (p<0.001) and percentage of male was higher (p<0.001) in the PC group. The PC group had higher DAS28 (3/CRP) (p<0.001) and poorer physical function (p<0.001), and received lower dosage of methotrexate (p<0.001). Percentage of patients receiving prednisolone (PSL) more than 7.5mg/day (p=0.001) and that of patients who had diabetes mellitus (DM) (p<0.001) were also higher in the PC group. There were 65 SIs (40 for pulmonary, 11 for skin and subcutaneous tissue, 14 other infections) in the PC group, and 89 SIs (42 for pulmonary, 21 for skin and subcutaneous tissue, 26 other infections) in the non-PC group. The crude incidence rate ratios comparing the PC group with the non-PC group were 2.8 (2.1-4.0) for all SIs and 3.7 (2.4-5.8) for pulmonary infections. Multivariate analyses revealed that age by decade (HR [95% CI], 1.8 [1.4-2.3]), presence of DM (1.9 [1.0-3.4]) and use of PSL ≥7.5mg/day (2.1 [1.2-3.7]) were significant risk factors for SIs in the PC group, while age by decade (1.5 [1.1-2.0]), Steinbrocker’s stage (III or IV) (1.9 [1.0-3.4]), and DAS28 (3/CRP) (1.4 [1.1-1.7]) in the non-PC group. HR of higher dosage of PSL in the PC group and those of biologics in both groups were not significant. Conclusions Different risk factors were associated with SIs between RA patients with and without PC. Disclosure of Interest R. Sakai: None Declared, M. Tanaka: None Declared, T. Nanki: None Declared, H. Yamazaki: None Declared, K. Watanabe: None Declared, R. Koike: None Declared, N. Miyasaka Grant/Research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., MSD K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eizai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant for: Janssen Pharmaceutical K.K., Bristol Myers Squibb K.K., Otsuka Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Abbott Japan Co., Ltd., M. Harigai Grant/Research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Santen Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc., Consultant for: Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Santen Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc.
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background The introduction of tumor necrosis factor inhibitors (TNFI) has dramatically improved treatments for rheumatoid arthritis (RA) during the last decade. To identify optimal use of TNFI in clinical practice, various clinical trials and all-cases postmarketing surveillance programs have been implemented in Japan1-4. However, change of benefit-risk balance of treatment with TNFI has not been investigated. Objectives To investigate changes of safety and effectiveness of treatment with TNFI over time. Methods This study included Japanese RA patients who started TNFI from 2005 to 2007 (2005 group, n=716, 634.2patient-years [PY]) and from 2008 to 2011 (2008 group, n=353, 270.6PY) as the first biologic therapy after their enrollment in the REAL database. Types and incidence rates of serious adverse events (SAE) during the first year of TNFI treatment were analyzed. Incidence rates (IR) were calculated with 95% confidence intervals (CI). To estimate the risk for serious infections (SI), the Cox proportional hazard model was applied. Changes in DAS28 (3/CRP) from baseline to year 1 (⊿DAS28) were compared between the two groups using Student’s t test to evaluate the effectiveness of TNFI. Results At baseline, compared to the 2005 group, the 2008 group had shorter disease duration (p<0.001) and lower disease activity (p<0.001), and was treated with higher dosages of methotrexate (p<0.001) and lower dosage of oral corticosteroids (p<0.001). The rate of previous use of three or more non-biological DMARDs was lower in the 2008 group (p=0.001). The crude IR ratios comparing the 2008 group with the 2005 group for SAE and SI were 0.93 (95% CI 0.65-1.34) and 0.50 (0.24-1.03), respectively. The Cox proportional hazards analysis revealed that the 2008 group had significantly lower risk for SI than the 2005 group (HR: 0.45 [95% CI, 0.21-0.97]) after adjusting for baseline characteristics. Although mean DAS28 (3/CRP) at baseline and year 1 in the 2005 group was significantly higher than the 2008 group (p=0.001), no significant differences in ⊿DAS28 were observed between the two groups (p=0.770). Conclusions The risk for SI in RA patients receiving TNFI significantly decreased after adjusting for baseline data without changes in the effectiveness. This observation could be explained, at least in part, by enlightenment of safety profile of TNFI and evidence-based risk management during treatment with TNFI. References Acknowledgements The affiliates that contributed to this work were: Hokkaido University, Juntendo University, Kagawa University, Keio University, Kobe University, Kyoto University, Nagasaki University, National Hospital Organization Nagasaki Medical Center, Ome Municipal General Hospital, Sagamihara National Hospital, Saitama Medical Center, Sasebo Chuo Hospital, The University of Tokyo, Tokyo Kyosai Hospital, Tokyo Medical University Hospital, Tokyo Metropolitan Bokutoh Hospital, Tokyo Metropolitan Geriatric Hospital, Tokyo Women’s Medical University, University of Occupational and Environmental Health, University of Tsukuba, Yokohama City Minato Red Cross Hospital, and Yokohama City University, (in alphabetical order). We sincerely thank all the rheumatologists and others caring for RA patients enrolled in the REAL registry. Disclosure of Interest R. Sakai: None Declared, S.-K. Cho: None Declared, M. Tanaka: None Declared, T. Nanki Grant/research support from: Eisai.Co., Ltd., H. Yamazaki: None Declared, K. Watanabe: None Declared, R. Koike: None Declared, N. Miyasaka Grant/research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., MSD K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., and Teijin Pharma Ltd., M. Harigai Grant/research support from: Abbot Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., LLtd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Santen Phrmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc., Speakers bureau: Abbot Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., LLtd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Santen Phrmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc.
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Objective: To compare the incidence and risk factors of serious adverse events (SAEs) in rheumatoid arthritis (RA) patients treated with etanercept (ETN) or adalimumab (ADA) between Korean and Japanese registries. Methods: We recruited 416 RA patients [505.2 patient-years (PYs)] who started ETN or ADA from Korean registry and 537 RA patients (762.0 PY) from Japanese registry. The patient background, incidence rate (IR) of SAE in 2 years, and risk factors for SAEs were compared. Results: Korean patients were younger and used more nonbiologic DMARDs, higher doses of methotrexate, and lower doses of prednisolone (PSL). The IR of SAEs (/100 PY) was higher in the Japanese registry compared to the Korean [13.65 vs. 6.73]. In both registries, infection was the most frequently reported SAE. The only significant risk factor for SAEs in Korean registry was age by decade [1.45]. In Japanese registry, age by decade [1.54], previous use of nonbiologic DMARDs ≥ 4 [1.93], and concomitant use of oral PSL ≥ 5 mg/day [2.20] were identified as risk factors for SAEs. Conclusions: The IR of SAE in Japan, especially infection, was higher than that of Korea, which was attributed to the difference of demographic and clinical characteristics of RA patients and treatment profiles.
    No preview · Article · Dec 2013 · Modern Rheumatology
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    ABSTRACT: Objectives: To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab. Methods: We conducted a multicenter, retrospective, case-control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected. Results: For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died. Conclusions: PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.
    Full-text · Article · Dec 2012 · Modern Rheumatology
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    ABSTRACT: Objective To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). Method This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan–Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. Results The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. Conclusions Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.
    No preview · Article · Apr 2012 · Annals of the rheumatic diseases
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    ABSTRACT: To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database. We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.1 PY) at the time of enrollment in the REAL. We assessed the occurrence of SIs within a 3-year observation period, including the period after switching to other TNF antagonists, and all SIs, unlimited to the first one in each patient as reported in other studies, to evaluate the real safety of TNF antagonists in daily practice. The incidence rate of SIs per 100 PY was 5.54 (95% confidence interval [95% CI] 4.44-6.84) in the anti-TNF group and 2.72 (95% CI 1.87-3.83) in the unexposed group. Poisson regression analysis revealed that the relative risk (RR) of continuous use of TNF antagonists for SIs after adjusting for baseline and time-dependent covariates was significantly elevated both overall (1.97, 95% CI 1.25-3.19) and for the first year (2.40, 95% CI 1.20-5.03), but not for the second and third years combined (1.38, 95% CI 0.80-2.43). The adjusted RR for SIs of etanercept compared to infliximab was not significantly elevated. Continuous anti-TNF therapy was significantly associated with increased risks for developing SIs during, but not after, the first year.
    Full-text · Article · Mar 2012
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    ABSTRACT: Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. Methods We conducted a multicenter, case–control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.
    No preview · Article · Feb 2012 · Modern Rheumatology
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    ABSTRACT: To compare tumor necrosis factor-α (TNF-α) inhibitors to nonbiological disease-modifying antirheumatic drugs (DMARD) for the risk of serious infection in Japanese patients with rheumatoid arthritis (RA). Serious infections occurring within the first year of the observation period were examined using the records for patients recruited to the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety (REAL), a hospital-based prospective cohort of patients with RA. The analysis included 1144 patients, 646 of whom were treated with either infliximab or etanercept [exposed group: 592.4 patient-years (PY)]. The remaining 498 patients received nonbiological DMARD with no biologics (unexposed group: 454.7 PY). In the unexposed group, the incidence rate for all serious adverse events (SAE) was 9.02/100 PY and for serious infections, 2.64/100 PY. In the exposed group, SAE occurred in 16.04/100 PY and serious infections in 6.42/100 PY. The crude incidence rate ratio comparing serious infections in the exposed group with the unexposed group was 2.43 (95% CI 1.27-4.65), a significant increase. A multivariate analysis revealed that the use of TNF inhibitors is a significant independent risk factor for serious infection (relative risk 2.37, 95% CI 1.11-5.05, p = 0.026). Our study has provided the first epidemiological data on Japanese patients with RA for the safety of TNF inhibitors compared to nonbiological DMARD for up to 1 year of treatment. Anti-TNF therapy was associated with a significantly increased risk for serious infections, compared to treatment with nonbiological DMARD.
    No preview · Article · Apr 2011 · The Journal of Rheumatology

  • No preview · Article · Feb 2011 · Modern Rheumatology