Hideki Origasa

Toyama University, Тояма, Toyama, Japan

Are you Hideki Origasa?

Claim your profile

Publications (143)615.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents.Methods and Results:The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8±9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value. Conclusions: The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan.
    No preview · Article · Feb 2016 · Circulation Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To evaluate the safety and effectiveness of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) in real-world clinical settings in Japan. Methods: Paediatric patients with sJIA initiating TCZ between April 2008 and February 2012 and those previously enrolled in clinical trials who initiated TCZ before April 2008 were enrolled in a Japanese registry surveillance programme. Safety and effectiveness parameters were collected for 52 weeks. Results: Of 417 patients enrolled, mean age was 11.2 years and 48.0% were female. TCZ exposure was 407.0 patient-years (PYs). Baseline corticosteroid use was higher than in clinical trials. Rates of total adverse events (AEs) and serious AEs (SAEs) were 224.3/100 PYs and 54.5/100 PYs, respectively, with SAEs higher than previously reported. The most frequent AEs and SAEs were infections and infestations (69.8/100 PYs and 18.2/100 PYs, respectively). 74 serious infections occurred in 55 patients (18.2/100 PYs); higher than previously reported. 26 macrophage activation syndrome events were reported in 24 patients (6.4/100 PYs). Fever and rash symptoms improved from baseline to week 52 (54.6% to 5.6% and 43.0% to 5.6%, respectively). At 4 weeks, 8 weeks and 52 weeks, 90.5%, 96.2% and 99.0% of patients achieved normal C reactive protein levels (<0.3 mg/dL), respectively. Conclusions: These first real-world data demonstrated that TCZ was well tolerated, with acceptable safety and effectiveness in patients with sJIA. Higher incidences of SAEs and serious infections may be due to differences, such as corticosteroid use and concomitant diseases, between patient populations enrolled in previously reported clinical trials and this study.
    Preview · Article · Dec 2015 · Annals of the rheumatic diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Prior ischemic stroke or transient ischemic attack (TIA) is a high risk for thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). To clarify rates of thromboembolic and hemorrhagic events, and target intensities of warfarin for secondary prevention, a subanalysis was performed using data from the J-RHYTHM Registry. Methods: Of 7937 outpatients with atrial fibrillation, 7406 with NVAF (men 70.8%, 69.8 ± 10.0 years) were followed for 2 years or until an event occurred. Event rates and effect of warfarin were compared between patients with (secondary prevention) and without (primary prevention) prior stroke/TIA. Results: Prevalence of male sex, diabetes mellitus, and mean age were higher in the secondary prevention group, showing a higher CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, and history of stroke or TIA) score than the primary prevention group (3.5 ± 1.0 versus 1.4 ± 1.0, P < .001). In the secondary prevention group, 93.4% of patients received warfarin and their time in therapeutic range was 62.8%. During follow-up, thromboembolism occurred more frequently in the secondary than in the primary prevention group (2.8% versus 1.5%, P = .004), especially in patients without warfarin. Major hemorrhage also occurred more frequently in the secondary prevention group (3.0% versus 1.7%, P = .006). Compared with patients not taking warfarin, combined rates of both events were lower at an international normalized ratio (INR) of 1.6-2.59 in patients taking warfarin in the secondary as well as in the primary prevention groups. Conclusions: Both thromboembolism and major hemorrhage occurred more frequently in NVAF patients with prior ischemic stroke/TIA. Target INR should be 1.6-2.59 for secondary as well as primary prevention of thromboembolism in Japanese NVAF patients.
    Preview · Article · Dec 2015 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Buerger disease is a rare disease of unknown etiology and cannot be treated by bypass surgery or percutaneous re-endovascularization. Although the need for effective limb ischemia prevention strategies is increasingly being recognized, effective preventative strategies are insufficient. The aim of this study using a new pulsed ultrasound device, SX-1001, is to determine whether treatment using SX-1001 can mitigate rest pain and improve blood supply to ischemic legs in patients with Buerger disease. This study is a multicenter, double-blinded, parallel randomized clinical trial testing the efficacy and safety of SX-1001. Treatment using SX-1001 is expected to result in reduction of the visual analog scale score for pain in Buerger disease patients who have Fontaine stage III. A total of 44 patients from 20 hospitals in Japan will be enrolled. The primary endpoint of the trial is a change in rest pain intensity on the visual analog scale score from baseline to 24 weeks. This trial will be the first to show the safety and efficacy of low-intensity pulsed ultrasound using SX-1001 for clinical symptoms in patients with Buerger disease. Low-intensity pulsed ultrasound may be a new therapy for limb ischemia. Ethical approval has been obtained from each of the participating institutes. Study findings will be disseminated through peer-reviewed journals and at scientific conferences.This study is registered at UMIN Clinical Trial Registry (UMIN000014757).
    Full-text · Article · Nov 2015 · International Heart Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Evidence increasingly points to the importance of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease (ESRD). Beraprost sodium (BPS) is an orally active prostacyclin (PGI2) analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition. Methods: This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120 μg/day or 240 μg/day) in Japanese patients with CKD. TRK-100STP was administered to a total of 112 patients. The primary efficacy endpoint was the difference in the slope of the regression line of reciprocal of serum creatinine (1/SCr) over time, obtained by the least-squares method. Results: Regarding the primary endpoint, statistical superiority of TRK-100STP 240 μg over placebo was not confirmed and so a recommended dose was not determined. Compared to placebo, however, the slope of regression line of 1/SCr, elevation of SCr and serum cystatin C during the treatment period revealed greater improvement at 120 μg, at both doses, and at 240 μg, respectively. In terms of safety, both TRK-100STP treatment groups were well tolerated. Conclusions: Although the study failed to meet the primary endpoint, results indicate that TRK-100STP may potentially prevent the decline in renal function of CKD patients independent of blood pressure or urinary protein levels. Trial registration: NCT02480751 . June 21, 2015.
    Preview · Article · Oct 2015 · BMC Nephrology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200mg every 2 weeks (Q2W) groups starting with LD (400mg Weeks 0/2/4) (LD group; J-RAPID: n=82, HIKARI: n=116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n=61, HIKARI: n=99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared to the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% vs. 4.9%; HIKARI: 17.2% vs. 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 vs. 315.7 J-RAPID, 282.6 vs. 321.3 HIKARI [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.
    Full-text · Article · Oct 2015 · Modern Rheumatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To clarify the effects of warfarin therapy in very old patients with non-valvular atrial fibrillation (NVAF), a post-hoc analysis was performed using the data of the J-RHYTHM Registry.Methods and Results:A consecutive series of AF outpatients was enrolled from 158 institutions. Of 7,937 patients, 7,406 with NVAF (men, 70.8%; 69.8±10.0 years) were followed for 2 years or until an event occurred. Patients were divided into 3 age groups (<70, 70-84, and ≥85 years) and 5 subgroups according to international normalized ratio (INR; <1.6, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Prevalence of female sex, permanent AF, hypertension, coronary artery disease, heart failure, and history of ischemic stroke/transient ischemic attack was higher in the older groups. In the oldest group, 79.7% of patients received warfarin and their time in therapeutic range, using the Japanese target INR of 1.6-2.6, was 67.1%. Rate of thromboembolic events was lower in the age groups <70 and 70-84 years (P=0.027 and P<0.001, respectively) for patients receiving warfarin compared with those who were not. In the oldest group, the rate of thromboembolism plus major hemorrhage was lower at INR 1.6-2.59. Warfarin could have beneficial effects even in very old NVAF patients if INR is kept between 1.6 and 2.59.
    Preview · Article · Sep 2015 · Circulation Journal

  • No preview · Article · Aug 2015 · International journal of cardiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined. This study examined stroke preventive effect of statin on 1578 patients who were assigned to pravastatin group (10 mg/day) or to control group. After 4.9 years of follow-up, although occurrence of total stroke and TIA was not different by the use of pravastatin, occurrence of atherothrombotic infarction was suppressed in the pravastatin group, raising a hypothesis that statins may reduce occurrence of stroke due to larger artery atherosclerosis.
    Full-text · Article · Aug 2015 · EBioMedicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. (NCT01451203). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Jul 2015 · Annals of the rheumatic diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There was no consistent recognition of the association between high or low body mass index (BMI) and health related quality of life (HRQL). The aim of this research was to study the association between BMI and HRQL in Chinese adults, and to further explore the stability of that association in the subgroup analysis stratified by status of chronic conditions. A total of 21,218 adults aged 18 and older were classified as underweight, normal weight, overweight, class I obese, and class II obese based on their BMI. HRQL was measured by the SF-36 Health Survey. The independent impact of each BMI category on HRQL was examined through standard least squares regression by comparing the difference of SF-36 scores and the minimum clinically important differences (MCID), which was defined as 3 points. Compared to the normal weight, the class I obese was significantly associated with better HRQL scores in the mental component summary (MCS) (75.1 vs. 73.4, P<0.001). The underweight had the lowest score in both the physical components summary (PCS) (75.4 vs. 77.5, P<0.001) and mental components summary (MCS) (71.8 vs. 73.4, P<0.001). For the MCID, the HRQL score was reduced by more than 3 points in the physical functioning for the class II obese (D=-3.43) and the general health for the underweight (D=-3.71). Stratified analyses showed a similar result in the health subjects and chronic conditions, and it was significant in the chronic conditions. The class I obese showed the best HRQL, especially in the mental domain. The worst HRQL was found in the underweight. The class II obese reduced HRQL in the physical functioning only. "Obesity paradox" was more obvious in the participants with chronic conditions.
    Preview · Article · Jun 2015 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, direct-acting oral anticoagulants (DOACs) have been introduced, with increasing use in patients with non-valvular atrial fibrillation (NVAF). However, warfarin continues to be widely used and the benefits and risks of warfarin in NVAF patients warrant closer inspection. Thromboembolism, major hemorrhage, and total and cardiovascular mortalities were analyzed in 7,406 NVAF patients in the J-RHYTHM Registry from January to July 2009, prior to DOAC introduction. Propensity score matching analysis was performed to reduce the differences in clinical characteristics between non-anticoagulant (n=1002) and warfarin (n=6404) cohorts to reassess warfarin outcomes over 2years. The incidence of thromboembolism was significantly greater in the non-anticoagulant cohort (3.0%) than in the warfarin cohort (1.5%, P<0.001) with less frequent major hemorrhage in the non-anticoagulant cohort (0.8%) than in the warfarin cohort (2.1%, P=0.009). Using propensity score matching, new subsets (n=896 each) were obtained, with matching of the clinical characteristics between warfarin and non-anticoagulant subsets. The warfarin subset had lower risk factors compared with the total warfarin cohort. The incidence of thromboembolism was higher in the non-anticoagulant subset (2.9%) than in the warfarin subset (0.7%, P<0.001). However, major hemorrhage was not significantly different between the two subsets. Although warfarin was associated with a significantly higher incidence of hemorrhage in the unmatched cohorts, propensity score matching revealed that warfarin reduced thromboembolism without a significant increase in hemorrhage in the matched subsets with lower risks. Propensity score matching reduced selection bias and provided rational comparisons although it had indwelling limitations. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jun 2015 · Thrombosis Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives To evaluate the long-term safety of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Japan. Methods In this long-term extension of the single-arm, observational postmarketing surveillance of TCZ, patients who received at least 1 dose of intravenous TCZ (8 mg/kg) between April 2008 and August 2010 were observed for 3 years. Patient characteristics and the incidences of mortality, serious infection, malignancy, GI perforation and serious cardiac dysfunction were evaluated. Data were summarized as the proportion (95% CI) of patients experiencing each event or as incidence rates presented as the number of patients per 100 patient-years (PY). Results In total, 5573 patients were enrolled, with a total observation of 15,106 PY. The mean and median treatment duration was 2.1and 2.9 years, respectively. The overall mortality rate during the observation period was 2.58% (144/5573 patients). The most common cause of death was infection (28.47%). The standardized mortality ratio (SMR) in comparison with the general Japanese population was 1.27 (95% CI, 1.08–1.50), which is comparable to the SMR reported in a large observational cohort of Japanese patients with RA (all-patient mortality between 1.46 [95% CI, 1.32–1.60] and 1.90 [95% CI, 1.75–2.07]).1 The incidence rate of malignancy during the observation period was 2.24% (0.83/100 PY), and the standardized incidence ratio (SIR) was 0.79 (95% CI, 0.66–0.95), which was stable over time. Only malignant lymphoma had a significantly higher incidence compared to the general Japanese population, with a SIR of 3.13 (95% CI, 1.82–5.39) which is comparable to that of all RA patients compared with the general population (SIR, 6.07; 95% CI, 3.71–9.37).2 There was no increase in rate of any AEs with prolonged observation, while incidence of fatal events, serious infection, GI perforation and serious cardiac dysfunction decreased over time (Table 1). Conclusions The safety profile of TCZ was consistent over time with respect to mortality, serious infections, malignancy, gastrointestinal perforation, and serious cardiac dysfunction. These data confirm the long-term safety of TCZ use in patients with RA in a real-world clinical setting in Japan. References Disclosure of Interest K. Yamamoto Grant/research support from: AbbVie, Astellas, BMS, Daiichi-Sankyo, Mitsubishi-Tanabe, Pfizer, Sanofi, Santen, Takeda and Teijin, Consultant for: AbbVie, Astellas, BMS, Boehringer Ingelheim, Chugai, Eisai, Ono, Pfizer, Santen, Taisho Toyama and UCB, Speakers bureau: AbbVie, Asahi Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Santen, Taisho Toyama, Takeda, Teijin and UCB., H. Goto Consultant for: Chugai, K. Hirao Grant/research support from: BIOTRONIK, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Japan Lifeline and MSD, Consultant for: BIOTRONIK, Boehringer-Ingelheim and Chugai, Speakers bureau: Bayer, BIOTRONIK, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Japan Lifeline and MSD, A. Nakajima Consultant for: AbbVie, Astellas, Chugai, Mitsubishi-Tanabe, Ono, Pfizer Santen and Takeda, H. Origasa Consultant for: Chugai, Astellas and UCB, A. Nakasone Employee of: Chugai, N. Takagi Employee of: Chugai, K. Totsuka Consultant for: Bayer, Chugai, Eiken Chemical, Kyorin and Toyama Chemical
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The C-OPERA study (NCT01451203) demonstrated better clinical outcomes of certolizumab pegol (CZP)+MTX compared to placebo (PBO)+MTX in Japanese MTX-naïve early RA patients (pts) with poor prognostic factors.1 Objectives To identify factors associated with better outcomes of CZP+MTX compared to PBO+MTX at 1 year using subgroup analyses by baseline (BL) factors. Methods Pts with ≤12 months persistent RA fulfilling 2010 ACR/EULAR classification criteria2 were enrolled in C-OPERA, a multicenter, double-blind, randomized study. Pts were MTX-naïve, with moderate disease activity (DAS28[ESR]≥3.2), positive ACPA (≥3xULN), and either RF positive or had bone erosion on radiographs of hands/feet. Pts were randomized 1:1 to CZP+MTX or PBO+MTX. CZP 400mg was administered at Weeks (Wks) 0, 2, and 4, followed by CZP 200mg Q2W to Wk52. Unless precluded by tolerability, MTX was started at 8mg/wk and escalated to 16mg/wk over 8 wks. We report association of BL parameters and mean MTX dose with radiographic progression (change from BL [CFB] in modified total Sharp score [mTSS]) and clinical remission (DAS28<2.6) at Wk52. Results In PBO+MTX arm, higher BL DAS28, CRP, mTSS, HAQ-DI and serum MMP-3 were associated with greater radiographic progression at Wk52, whereas CZP+MTX still inhibited progression of structural damage in these pts despite higher risk of progression.3 No positive trend of MTX dose with inhibitory effect on CFB in mTSS was observed overall. In the PBO+MTX arm, higher BL DAS28 and CRP were associated with lower DAS28 remission rate at Wk52, suggesting BL factors associated with either radiographic progression or disease activity may differ. Lower dose MTX group (8–≤12mg/wk) showed lower DAS28 remission rate compared to high dose group (>12–16mg/wk) (30.5% vs 42.9%). DAS28 remission rate was higher in CZP+MTX compared to PBO+MTX, particularly in pts with high BL parameters. Conclusions CZP+MTX showed better clinical outcomes compared to PBO+MTX, particularly in pts with higher risk of progression identified by BL factors. Therefore, this subgroup of MTX-naïve early RA pts may need combination treatment with CZP+MTX to inhibit progression of structural damage. References Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest T. Atsumi Speakers bureau: Astellas, Bristol-Myers, Chugai and Mitsubishi-Tanabe, K. Yamamoto Grant/research support from: UCB Pharma, Pfizer, Abbott, Santen, Mitsubishi-Tanabe and Eisai, Consultant for: UCB Pharma, Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe and Eisai, T. Takeuchi Grant/research support from: Abott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda and Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe and Asahi Kasei, Speakers bureau: UCB Pharma, Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, H. Yamanaka Grant/research support from: UCB Pharma, Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, Consultant for: UCB Pharma, Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, N. Ishiguro Grant/research support from: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken and Pfizer, Speakers bureau: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Taisho-Toyama and Otsuka, Y. Tanaka Grant/research support from: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie, Daiichi-Sankyo, Consultant for: UCB Pharma, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, Speakers bureau: UCB Pharma, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, K. Eguchi Consultant for: UCB Pharma, A. Watanabe Grant/research support from: Daiichi-Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical and Meiji Seika, Speakers bureau: SD, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe, Pfizer, H. Origasa Consultant for: UCB Pharma and Astellas, T. Shoji Employee of: UCB Pharma, O. Togo Employee of: UCB Pharma, T. Okada Employee of: Astellas, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv., N. Miyasaka Grant/research support from: Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai and Astellas, T. Koike Consultant for: Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin, UCB Pharma, Speakers bureau: UCB Pharma, Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin and Daiichi-Sankyo
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the longterm safety of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Japan. In this longterm extension of a single-arm, observational postmarketing surveillance study, a total of 5573 patients who initiated intravenous TCZ between April 2008 and July 2009 were observed for 3 years, regardless of its continuation, for incidence of fatal events, serious infections, malignancy, gastrointestinal perforations, and serious cardiac dysfunction. Of the 5573 patients who were enrolled, 4527 patients (81.23%) completed 3 years of followup. There were no increases in the proportions of patients with fatal events, serious infection, malignancy, GI perforation, or serious cardiac dysfunction over 3 years. The all-cause mortality rate during followup was 2.58% (0.95/100 patient-yrs), and the standardized mortality ratio was 1.27 (95% CI, 1.08 to 1.50). Patients who were older with longer disease duration and respiratory comorbidities were more likely to discontinue TCZ treatment following serious infection during the first year. Among patients who completed 3 years of TCZ treatment, serious infection developed at a constant rate during the 3-year treatment period. The proportion of malignancy during followup was 2.24% (0.83/100 patient-yrs), and the standardized incidence ratio was 0.79 (95% CI, 0.66 to 0.95). The safety profile of TCZ was consistent over time regarding mortality, serious infections, malignancy, gastrointestinal perforation, and serious cardiac dysfunction. These data confirm the longterm safety of TCZ use in patients with RA in a real-world clinical setting.
    No preview · Article · Jun 2015 · The Journal of Rheumatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Because the current Japanese guideline recommends CHADS2score-based risk stratification in nonvalvular atrial fibrillation (NVAF) patients and does not list female sex as a risk for thromboembolic events, we designed the present study to compare the CHA2DS2-VASc and CHA2DS2-VA scores in the J-RHYTHM Registry.Methods and Results:We prospectively assessed the incidence of thromboembolic events for 2 years in 997 NVAF patients without warfarin treatment (age 68±12 years, 294 females). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for thromboembolic events was evaluated by c-statistic difference and net reclassification improvement (NRI). Thromboembolic events occurred in 7/294 females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72 for female to male, 95% confidence interval (CI) 0.28-1.62, P=0.44). No sex difference was found in patient groups stratified by CHA2DS2-VASc and CHA2DS2-VA scores. There were significant c-statistic difference (0.029, Z=2.3, P=0.02) and NRI (0.11, 95% CI 0.01-0.20, P=0.02), with the CHA2DS2-VA score being superior to the CHA2DS2-VASc score. In patients with CHA2DS2-VASc scores 0 and 1 (n=374), there were markedly significant c-statistic difference (0.053, Z=6.6, P<0.0001) and NRI (0.11, 95% CI 0.07-0.14, P<0.0001), again supporting superiority of CHA2DS2-VA to CHA2DS2-VASc score. In Japanese NVAF patients, the CHA2DS2-VA score, a risk scoring system excluding female sex from CHA2DS2-VASc, may be more useful in risk stratification for thromboembolic events than CHA2DS2-VASc score, especially in identifying truly low-risk patients.
    Preview · Article · May 2015 · Circulation Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Monotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com; ClinicalTrials.gov identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy. The CSPS.com is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8-180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year. The primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events. The CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol. © 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.
    Full-text · Article · Dec 2014 · International Journal of Stroke
  • [Show abstract] [Hide abstract]
    ABSTRACT: Object: A modified World Federation of Neurosurgical Societies scale (m-WFNS scale) for aneurysmal subarachnoid hemorrhage (SAH) recently has been proposed, in which patients with Glasgow Coma Scale (GCS) scores of 14 are assigned to grade II and those with GCS scores of 13 are assigned to grade III regardless of the presence of neurologic deficits. The study objective was to evaluate outcome predictability of the m-WFNS scale in a large cohort. Methods: This was a multicenter prospective observational study conducted in Japan. A total of 1656 patients with SAH were registered during the 2.5-year study period, and the outcome predictability, using the Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) scores at discharge and at 90 days after onset, was evaluated by comparing the m-WFNS with the original WFNS scale. We focused on whether significant differences in these scores were present between the neighboring grades. Results: In the m-WFNS scale, significant difference between any neighboring grades was observed both in the mean GOS and mRS scores at 90 days except between grades III/IV. However, differences were not significant between grades II/III and between grades III/IV in the original WFNS scale. Conclusions: SAH-induced brain injury may be substantially severer in patients with GCS 13 than those with GCS 14, which may explain why grade III patients faired significantly worse than grade II patients by the modified WFNS scale. Although further validation is necessary, the m-WFNS scale has a potential of providing neurosurgeons with simpler and more reliable prognostication of patients with SAH.
    No preview · Article · Dec 2014 · World Neurosurgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial. Methods/design: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand. A total of 750 patients (n = 250 per group) with primary glomerular disease or nephrosclerosis were planned to be enrolled. Patients were randomized into one of three treatment groups in a double-bind, placebo-controlled manner: TRK-100STP 60 μg b.i.d.; TRK-100STP 120 μg b.i.d.; or placebo. The treatment period is planned to last 2 to 4 years. The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD (dialysis induction, renal transplantation, or increase in SCr to ≥ 6.0 mg/dL). Discussion: This trial targeting CKD patients is designed to (a) demonstrate the superiority of TRK-100STP over placebo using renal composite endpoints, (b) determine the recommended clinical dose, and (c) assess the safety of TRK-100STP in this population and setting. Trial registration: ClinicalTrials.gov Identifier: NCT01090037.
    Full-text · Article · Sep 2014 · BMC Nephrology

  • No preview · Article · Sep 2014 · Cerebrovascular Diseases

Publication Stats

3k Citations
615.64 Total Impact Points

Institutions

  • 2007-2015
    • Toyama University
      Тояма, Toyama, Japan
    • University of Toyama
      • • Department of Internal Medicine 3
      • • Graduate School of Medicine and Pharmaceutical Science for Education
      • • Department of Internal Medicine 1
      • • Department of Neurosurgery
      Тояма, Toyama, Japan
    • Sakakibara Heart Institute
      Фучу, Tōkyō, Japan
  • 2010
    • Hiroshima University
      • Department of Cardiovascular Physiology and Medicine
      Hiroshima-shi, Hiroshima-ken, Japan
  • 2002-2006
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan
  • 2005
    • Kanazawa University
      • Department of Internal Medicine
      Kanazawa, Ishikawa, Japan
  • 2004
    • Kyoto University
      • Department of Cardiovascular Medicine
      Kyoto, Kyoto-fu, Japan
  • 2003
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan