Hideki Origasa

University of Toyama, Тояма, Toyama, Japan

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Publications (124)558.75 Total impact

  • International journal of cardiology 08/2015; 201. DOI:10.1016/j.ijcard.2015.08.059 · 6.18 Impact Factor
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    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.
    Annals of the rheumatic diseases 07/2015; DOI:10.1136/annrheumdis-2015-207511 · 10.38 Impact Factor
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    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.
    Thrombosis Research 06/2015; DOI:10.1016/j.thromres.2015.06.009 · 2.43 Impact Factor
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    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.
    The Journal of Rheumatology 06/2015; DOI:10.3899/jrheum.141210 · 3.17 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):716.2-717. DOI:10.1136/annrheumdis-2015-eular.1501 · 10.38 Impact Factor
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    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.
    Circulation Journal 05/2015; DOI:10.1253/circj.CJ-15-0095 · 3.69 Impact Factor
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    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.
    International Journal of Stroke 12/2014; 10(2). DOI:10.1111/ijs.12420 · 4.03 Impact Factor
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    ABSTRACT: Abstract OBJECTIVE: A modified World Federation of Neurosurgical Societies scale (m-WFNS scale) for aneurysmal subarachnoid hemorrhage (SAH) has recently 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 is a multi-center prospective observational study conducted in Japan. A total of 1656 SAH patients 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 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 SAH patients.
    World Neurosurgery 12/2014; 83(5). DOI:10.1016/j.wneu.2014.12.032 · 2.42 Impact Factor
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    ABSTRACT: 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 120 mug b.i.d.; TRK-100STP 60 mug 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).
    BMC Nephrology 09/2014; 15(1):153. DOI:10.1186/1471-2369-15-153 · 1.52 Impact Factor
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    ABSTRACT: Background:It is disputed whether the risk of cardiogenic embolism varies with type of atrial fibrillation (AF). Although several studies have found that the risk of cardiogenic embolism was similar among paroxysmal and persistent/permanent AF, a few studies have found that patients with paroxysmal AF had a lower rate of stroke and systemic embolism than those with persistent/permanent AF. In the present study, post-hoc analysis of the J-RHYTHM Registry was done to compare the risk of thromboembolic events among 3 types of non-valvular AF (NVAF).Methods and Results:A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, warfarin was used for 78.6%, 90.0%, and 91.8% of patients with paroxysmal, persistent, and permanent AF, respectively. There were 126 thromboembolic events during the follow-up period. The crude event rate was 2-fold higher among the patients with permanent NVAF (2.29%) than among those with paroxysmal (1.16%) or persistent (1.20%) NVAF (P=0.001). After adjusting for warfarin use and CHA2DS2-VASc score components, however, the hazard ratio for thromboembolism did not differ between paroxysmal (reference) and permanent NVAF (1.007; 95% confidence interval: 0.955-1.061).Conclusions:The crude rate of thromboembolic events was higher in permanent NVAF than in paroxysmal NVAF, but after adjusting for warfarin use and CHA2DS2-VASc score components, paroxysmal and permanent NVAF patients had similar risk of thromboembolism.
    Circulation Journal 08/2014; 78(10). DOI:10.1253/circj.CJ-14-0507 · 3.69 Impact Factor
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    ABSTRACT: Background To maximize protection against stroke with minimal bleeding, warfarin therapy in nonvalvular atrial fibrillation (NVAF) requires tight control within a narrow therapeutic range, which might depend on racial variations. Methods The J-RHYTHM Registry followed 6404 NVAF patients treated with warfarin for 2 years. Using international normalized ratios (INRs) at or closest to the embolic and intracranial hemorrhagic (ICH) events, we determined odds ratios for ischemic stroke/systemic embolism (SE) and ICH according to any given INR with a reference INR range including 2.0. Results Ischemic stroke and SE occurred in 97 of the patients and ICH occurred in 49. The estimated INR-risk relationships showed characteristics of Japanese NVAF patients. Compared to INR-risk relationships reported for Westerners, those observed in Japanese patients were virtually identical for ischemic stroke/SE and shifted leftward by approximately 0.5 INR for ICH. Conclusion This is the largest Japanese study providing fundamental data necessary to establish optimal anticoagulation intensities. Japanese NVAF patients may require narrower therapeutic ranges than Westerners.
    Journal of Cardiology 08/2014; 65(3). DOI:10.1016/j.jjcc.2014.07.013 · 2.57 Impact Factor
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    ABSTRACT: Background Certolizumab pegol (CZP) has demonstrated rapid and sustained improvements in disease activity in Japanese patients (pts) with active rheumatoid arthritis (RA), both with methotrexate (J-RAPID; NCT00791999) and with or without DMARDs other than methotrexate (HIKARI; NCT00791921) in placebo-controlled double-blind (DB) randomized trials.1,2 Although previous analysis suggested that the loading dose (LD) of CZP (400mg at Weeks (Wks) 0, 2 and 4) improves the clinical response of CZP for the first 24 wks3, the impact of the initial LD on the long-term outcomes remains unknown. Objectives To compare the safety, efficacy and immunogenicity 1 year (yr) after initiation of CZP with and without the LD. Methods Data from the Japanese clinical trials1,2 and the respective open-label extensions (OLEs) (J-RAPID OLE: NCT00851318; HIKARI OLE: NCT00850343)4,5 were used for this analysis. Pts randomized to receive CZP 200mg every 2 wks (Q2W) with the LD were defined as LD groups (J-RAPID: n=82; HIKARI: n=116), whereas pts randomized to receive placebo in the DB trials who entered the respective OLEs and initiated CZP 200mg Q2W without LD were defined as No-LD groups (J-RAPID: n=61; HIKARI: n=99). The ACR response rates, achievement of DAS28 LDA, safety assessments, plasma CZP levels and rates of anti-CZP antibodies (Abs) were analyzed up to 1yr after initiating CZP. DB baseline for the LD groups and at OLE entry for the No-LD groups were used as the baselines. Results The ACR20/50/70 responses of the LD vs No-LD groups in J-RAPID were 74.4%/62.2%/32.9% vs 76.8%/60.7%/26.8%, and in HIKARI were 69.0%/50.9%/31.9% vs 62.1%/43.2%/23.2%, respectively, at 1yr (Figure). The LD groups had higher proportion of pts in DAS28 LDA (J-RAPID: 48.8% vs 42.6%; HIKARI: 42.2% vs 26.3%). Frequency of anti-CZP Abs was lower in the LD groups than in the No-LD groups (J-RAPID: n=2/82 [2.4%] vs n=4/61 [6.6%]; HIKARI: n=30/116 [25.9%] vs n=32/99 [32.3%]). Pts who developed anti-CZP Abs had lower plasma CZP levels and lower clinical responses than Ab-negative pts. Safety profiles were similar between the groups. Conclusions While this post-hoc analysis has limitations including the comparison of DB vs OLE data, the results suggest that the benefits potentially due to the initial loading dose are sustained until at least 1yr without additional risk of adverse events. References Acknowledgements The authors acknowledge Costello Medical Consulting for editorial assistance which was funded by UCB Pharma. Disclosure of Interest : T. Takeuchi Grant/research support: Abbott Japan, Astellas Pharma, Bristol–Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Pfizer Japan, Sanofi–Aventis, Santen, Takeda, Teijin Pharma, Abbvie, Asahikasei, Taisho-Toyama, Consultant for: Astra Zeneca, Eli Lilly Japan, Novartis, Mitsubishi Tanabe, Asahi Kasei Medical, Abbvie, Daiichi Sankyo, Speakers bureau: Abbott Japan, Bristol–Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer Japan, Takeda, Astellas Pharma, Diaichi Sankyo, K. Yamamoto Grant/research support: UCB Pharma, Pfizer, Abbott, Santen, Mitsubishi-Tanabe, Eisai, Consultant for: UCB Pharma, Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe, Eisai, H. Yamanaka Grant/research support: AbbVie, Asahikasei Pharma, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin Pharma, Speakers bureau: AbbVie, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Pfizer, Takeda, Teijin Pharma, N. Ishiguro Grant/research support: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken and Pfizer, Daiichi Sankyo, Speakers bureau: Daiichi Sankyo, Takeda, Hisamitsu, Otsuka, Taisho-Toyama, Kaken, Eisai, Janssen, Bristol-Myers Squibb, Abbott Japan, Chugai, Mitsubishi Tanabe, UCB Japan, Astellas Pharma, Pfizer Japan, Y. Tanaka Grant/research support: Bristol-Myers Squibb, Mitsubishi-Tanabe, Abbvie, MSD, Chugai, Astellas, Daiichi-Sankyo, Consultant for: Mitsubishi-Tanabe, Eisai, Chugai, Abbott Japan, Astellas, Daiichi-Sankyo, Abbvie, Janssen, Pfizer, Takeda, Astra-Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi-Kasei, Speakers bureau: Mitsubishi-Tanabe, Eisai, Chugai, Abbott Japan, Astellas, Daiichi-Sankyo, Abbvie, Janssen, Pfizer, Takeda, Astra-Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi-Kasei, K. Eguchi Consultant for: UCB Pharma, A. Watanabe Grant/research support: Daiichi-Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical and Meiji Seika, Speakers bureau: MSD, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe, Pfizer, H. Origasa Consultant for: UCB Pharma and Astellas, M. Kobayashi Employee of: UCB Pharma, T. Shoji Employee of: UCB Pharma, O. Togo Employee of: UCB Pharma, N. Miyasaka Grant/research support: Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai and Astellas, T. Koike Speakers bureau: UCB Pharma, Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin Pharma, Daiichi-Sankyo DOI 10.1136/annrheumdis-2014-eular.1447
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):247-247. DOI:10.1136/annrheumdis-2014-eular.1447 · 10.38 Impact Factor
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    ABSTRACT: Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer (Kiklin(®) Capsules) is a non-absorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study was a multicenter, double-blind, randomized, placebo-controlled study to confirm the superiority of bixalomer to placebo for a 4-week treatment period in patients with chronic kidney disease on hemodialysis with hyperphosphatemia. Sevelamer hydrochloride (HCl), a similar non-absorbable polymer, was used as an active comparator for open-label as a reference without statistical comparison for efficacy and safety. The primary endpoint was the change in serum phosphorus level from baseline. The safety profile was also investigated. The number of subjects was 32 in the placebo group and 31 in each bixalomer group (1.5, 3.0 and 4.5 g/day), respectively. The baseline serum phosphorus level was 7.95 to 8.25 mg/dL. Bixalomer showed a significant decrease in serum phosphorus level at all doses compared with placebo, and the adjusted mean change in serum phosphorus level from the baseline to the end of treatment (at Week 4 or at the time of discontinuation) was +0.24 mg/dL in the placebo group, -0.75 mg/dL in the 1.5 g/day group, -1.32 mg/dL in the 3.0 g/day group, and -1.80 mg/dL in the 4.5 g/day group, showing a dose-dependent decrease in serum phosphorus level. The mean change in serum phosphorus level was -2.32 mg/dL in the sevelamer HCl group under the mean dose of 4.8 g/day. Major adverse events included constipation, hard feces, vomiting, etc.; however, none of the adverse events were serious or severe. Consequently, the superiority of bixalomer to placebo and its dose-dependency for treating hyperphosphatemia were confirmed (Clinical trial registration: NCT00505037).
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 06/2014; 18 Suppl 2:24-32. DOI:10.1111/1744-9987.12202 · 1.53 Impact Factor
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    ABSTRACT: Objectives. A post-hoc analysis was performed to determine the relationship between the timing and magnitude of DAS28(ESR) response and long term outcomes in Japanese patients after 1 year of CZP treatment. Methods. Our analysis included 82 J-RAPID trial patients treated with CZP 200 mg and methotrexate, and 116 HIKARI trial patients treated with CZP 200 mg alone or with disease-modifying agents other than methotrexate. Remission rates and changes in mTSS at year 1 were compared to the DAS28(ESR) response at week 12 of CZP treatment. Results. After 1 year of treatment, remission was achieved in 41.3% of the J-RAPID and 34.9% of the HIKARI patients with a week 12 DAS28(ESR) response of ≥ 1.2. In comparison, patients with a DAS28(ESR) response of < 1.2 at week 12 only had a < 7% probability of achieving remission and displayed higher change in mTSS after 1-year treatment. Conclusions. The likelihood of remission and extent of radiographic progression after 1 year was associated with the week 12 DAS28(ESR) response. The DAS28(ESR) response at 12 weeks could be beneficial for identifying patients that are unlikely to respond to prolonged CZP treatment.
    Modern Rheumatology 05/2014; 25(1):1-10. DOI:10.3109/14397595.2014.904475 · 2.21 Impact Factor
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    ABSTRACT: Background: Recent European guidelines recommended the CHA2DS2-VASc score for thromboembolic and the HAS-BLED score for bleeding risk stratifications. We validated these scores in 7,384 Japanese patients with nonvalvular atrial fibrillation (NVAF) enrolled in the J-RHYTHM Registry. Methods and Results: Of the study cohort, 6,387 patients taking warfarin and the other 997 not taking warfarin were prospectively examined for 2 years. Thromboembolic and major bleeding risks were stratified by modified CHA2DS2-VASc (mCHA2DS2-VASc) and HAS-BLED (mHAS-BLED) scores, respectively. Of the patients with mCHA2DS2-VASc score 0, 1, and ≥2, thromboembolism occurred in 2/141 (0.7%/year), 4/233 (0.9%/year), and 24/623 (1.9%/year), respectively, in the non-warfarin group, and in 1/346 (0.1%/year, P=0.19 vs. non-warfarin), 4/912 (0.2%/year, P=0.05), and 92/5,129 (0.9%/year, P=0.0005), respectively, in the warfarin group. When female sex was excluded from the score, thromboembolism occurred in 2/180 patients (0.6%/year), 5/245 (1.0%/year), and 23/572 (1.6%/year), respectively, in the non-warfarin group, and in 1/422 (0.1%/year, P=0.20 vs. non-warfarin), 5/1,096 (0.2%/year, P=0.02), and 91/4,869 (0.9%/year, P=0.0005), respectively, in the warfarin group. Patients with mHAS-BLED scores ≥3 were at high risk for major bleeding irrespective of warfarin treatment (1.3 and 2.6%/year in the non-warfarin and warfarin groups, respectively). Conclusions: In Japanese NVAF patients, the mCHA2DS2-VASc score is useful for identifying patients at truly low risk of thromboembolism. Female sex may be excluded as a risk from the score. mHAS-BLED score ≥3 is useful for identifying patients at high risk of major bleeding.
    Circulation Journal 04/2014; 78(7). DOI:10.1253/circj.CJ-14-0144 · 3.69 Impact Factor
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    ABSTRACT: Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients. This was a multicenter, randomized open-label, non-inferiority study. The primary endpoint was serum phosphate on completion of treatment. Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level. Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day. Treatment was continued for 12 weeks. Fifty-five patients were randomized to each treatment group. After 12 weeks, the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group, with a difference of 0.31 mg/dL and 95% confidence interval (CI) of [−0.13 to 0.76]. The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was <1.0 mg/dL, which was the non-inferiority margin in this study. Thus, non-inferiority of bixalomer to sevelamer was confirmed. The incidence of adverse events was lower in the bixalomer group, and bixalomer did not promote acidosis. Bixalomer achieved a similar reduction of serum phosphate to sevelamer, while causing fewer adverse reactions. Consequently, the usefulness of bixalomer for treating hyperphosphatemia was confirmed.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2014; 18(2). DOI:10.1111/1744-9987.12068 · 1.53 Impact Factor
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    ABSTRACT: Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.
    Modern Rheumatology 03/2014; 24(5). DOI:10.3109/14397595.2014.881709 · 2.21 Impact Factor
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    ABSTRACT: Background This study examined the efficacy of certolizumab pegol (CZP) + MTX in Japanese patients (pts) with active RA and an inadequate response to MTX.1 Objectives To assess the impact of CZP on physical function, pain and HRQoL in patients with concomitant MTX. Methods In this 24-week (Wk), Phase II/III, multicenter, double-blind, randomised, placebo (PBO)-controlled, study, Japanese pts with active RA and an inadequate response to MTX were randomized (1:1:1:1) to CZP 100, 200, or 400mg +MTX, or PBO +MTX every 2 Wks. CZP pts received induction dosing with 200mg (100mg group) or 400mg (200 and 400mg groups) at Wks 0, 2, and 4. Pts who did not achieve an ACR20 response at Wks 12 and 14 were withdrawn from the study at Wk 16 and were eligible to enter an OLE study, as were pts completing the study. Primary efficacy end point was ACR20 response at Wk 12. Physical function was assessed with HAQ-DI and pain with VAS at each visit, and HRQoL with SF36 at Wks 12 and 24. ACR responses were assessed using NRI, and HAQ-DI, pain (VAS) and SF36 using LOCF. Results A total of 316 pts were randomized. Demographic and baseline (BL) characteristics were similar between treatment groups: average values for RA disease duration ranged from 5.6 to 6.0 years, DAS28(ESR) from 6.19 to 6.46, HAQ-DI from 1.12 to 1.19, and MTX dose from 7.4 to 7.6mg/Wk across groups. ACR20 response at Wk 12 in CZP 100, 200, 400mg and PBO groups was 62.5%, 76.8%, 77.6%, and 28.6%, respectively (p<0.001 each CZP group vs PBO). As early as Wk 1, HAQ-DI was significantly improved in the CZP group vs PBO. HAQ-DI change from BL at Wk 1 was -0.24, -0.28, and -0.22 in the CZP groups vs -0.01 in the PBO group (p<0.001 each CZP group vs PBO), and at Wk 24 was -0.43, -0.55, and -0.57 in the CZP groups vs -0.18 in the PBO group (p<0.01 each CZP group vs PBO). Pain (VAS) was also significantly improved; change from BL at Wk 1 was -17.3, -16.6 and -14.8 in CZP groups vs -3.9 in PBO group (p<0.001 each CZP group vs PBO), and at Wk 24 was -26.9, -27.9 and -31.9 in CZP groups vs -10.6 in PBO group (p<0.001 each CZP group vs PBO). CZP 200mg and 400mg showed significantly greater improvements in the SF36 physical and mental components vs PBO at Wks 12 and 24. Changes in physical and mental components summary scores from BL at Wk 24 were 8.87, 10.17 and 11.36 in 100mg, 200mg and 400mg CZP groups vs 4.27 in PBO group (P<0.01 each CZP group vs PBO), and 3.19, 5.58 and 5.84 in CZP groups vs 1.24 in PBO group (P<0.01 for 200mg and 400mg CZP group vs PBO). Conclusions Treatment with CZP + MTX resulted in a rapid and sustained reduction in RA signs and symptoms, and improved physical function, pain and HRQoL in Japanese RA patients with an inadequate response to MTX. Disclosure of Interest H. Yamanaka Grant/Research support from: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, K. Yamamoto Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, T. Takeuchi Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, N. Ishiguro Consultant for: Otsuka Pharmaceutical Co., Ltd, Y. Tanaka Consultant for: Otsuka Pharmaceutical Co., Ltd, K. Eguchi Consultant for: Otsuka Pharmaceutical Co., Ltd, A. Watanabe Consultant for: Otsuka Pharmaceutical Co., Ltd, H. Origasa Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, T. Shoji Employee of: Otsuka Pharmaceutical Co., Ltd, Y. Sakamaki Employee of: UCB Pharma, N. Miyasaka Consultant for: Otsuka Pharmaceutical Co., Ltd, T. Koike Consultant for: Otsuka Pharmaceutical Co., Ltd
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):664-664. DOI:10.1136/annrheumdis-2012-eular.468 · 10.38 Impact Factor
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    ABSTRACT: Background Physical function, pain and health-related quality of life (HRQoL) are important outcomes in RA. The HIKARI study examined the efficacy and safety of certolizumab pegol (CZP) in Japanese patients (pts) with active RA in whom methotrexate (MTX) could not be administered.1 Objectives To assess the impact of CZP on physical function, pain and HRQoL in the HIKARI study. Methods In this 24-week (Wk), Phase III, double-blind, randomized, placebo-controlled study, pts were randomized to CZP 200 mg (following induction dosing of 400 mg at Wks 0, 2, and 4) or placebo (PBO) every 2 Wks. Concomitant DMARDs other than MTX were permitted. Pts not achieving ACR20 at Wks 12 and 14 withdrew at Wk 16 and were eligible to enter an open-label extension, as were pts completing the study. Primary efficacy endpoint was ACR20 at Wk 12. Physical function was assessed with HAQ-DI and pain with VAS at each visit. HRQoL was evaluated with SF36 at Wks 12 and 24. ACR responses were assessed using NRI, and HAQ-DI, pain (VAS) and SF36 using LOCF. Results A total of 230 pts were randomized. Demographic and baseline characteristics were similar between CZP and PBO groups: mean RA disease duration was 5.4 and 5.8 years, mean HAQ-DI 1.05 and 1.21, and mean DAS28(ESR) 6.09 and 6.30, respectively. ACR20 response rates at Wk 12 in CZP and PBO groups were 67.2% and 14.9% (p<0.001) and at Wk 24 were 63.8% and 11.4% (p<0.001); ACR50 and ACR70 response rates were also significantly higher in the CZP group than in the PBO group at Wk 12 (ACR50: 37.9% vs 6.1%; ACR70:19.0% vs 0%) and Wk 24 (ACR50: 46.6% vs 6.1%; ACR70: 25.9% vs 0.9%). As early as Wk 1 HAQ-DI was improved in the CZP group compared to PBO; HAQ-DI change from baseline at Wk 1 was -0.30 in CZP group vs -0.01 in PBO group (p<0.001). At Wk 24 HAQ-DI change from baseline was -0.48 in CZP group vs 0.12 in PBO group (p<0.001). Pain (VAS) was also significantly improved; change from baseline at Wk 1 was -18.9 in CZP group vs -2.2 in PBO group, and at Wk 24 was -27.5 in CZP group vs -1.2 in PBO group (p<0.001 at both timepoints). CZP showed significantly greater improvements in both the physical and the mental components of the SF36 than PBO at Wks 12 and 24. Changes in physical and mental component summary scores from baseline at Wk 24 were 9.27 in CZP group vs -1.46 in PBO group (p<0.001), and 5.24 in CZP group vs -0.94 in PBO group (p<0.001). Conclusions Treatment with CZP resulted in a rapid and sustained reduction in RA signs and symptoms, and improved physical function and HRQoL in Japanese RA patients who could not be treated with MTX. Disclosure of Interest H. Yamanaka Grant/Research support from: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, K. Yamamoto Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, T. Takeuchi Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, N. Ishiguro Consultant for: Otsuka Pharmaceutical Co., Ltd, Y. Tanaka Consultant for: Otsuka Pharmaceutical Co., Ltd, K. Eguchi Consultant for: Otsuka Pharmaceutical Co., Ltd, A. Watanabe Consultant for: Otsuka Pharmaceutical Co., Ltd, H. Origasa Consultant for: Otsuka Pharmaceutical Co., Ltd, UCB Pharma, K. Iwai Employee of: Otsuka Pharmaceutical Co., Ltd, Y. Sakamaki Employee of: UCB Pharma, N. Miyasaka Consultant for: Otsuka Pharmaceutical Co., Ltd, T. Koike Consultant for: Otsuka Pharmaceutical Co., Ltd
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):i-664. DOI:10.1136/annrheumdis-2012-eular.469 · 10.38 Impact Factor
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    ABSTRACT: Background Early response to certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, has been shown to predict long-term probability of low disease activity and inhibition of progression of structural joint damage in patients (pts) with active rheumatoid arthritis (RA) from the RAPID 1 trial.1 Objectives To examine whether clinical response to CZP at Week (Wk)12 predicts long-term clinical remission and inhibition of progression of structural damage in Japanese pts with active RA. To explore the impact of concomitant DMARDs and baseline (BL) disease status. Methods 198 pts (J-RAPID [NCT00791999]2 82 pts; HIKARI [NCT00791921]3 116 pts) treated with CZP 200 mg every 2 wks were sub-grouped by concomitant medications and BL CRP (>1.8 vs ≤1.8 mg/L), DAS28 (>6.11 vs ≤6.11), and disease duration (>5 yrs vs ≤5 yrs). Remission rates and radiographic changes at Wk52 were compared to DAS28 responses obtained at Wk12. Pts in J-RAPID received concomitant MTX. Pts in HIKARI received DMARDs other than MTX or no concomitant DMARDs (“monotherapy”). Missing DAS28 data was imputed by last observation carried forward. Linear extrapolation was used to estimate the missing mTSS data at Wk52. Results In pts with a DAS28 change ≥1.2 at Wk12 (Responders, R), DAS28 remission was achieved at Wk52 in 41.3% of J-RAPID and 34.9% of HIKARI pts (Table). In comparison, pts with a DAS28 response of <1.2 at Wk12 (Non-responders, NR) only had 5.3% and 6.7% chance of achieving remission, respectively, and had higher rates of radiographic progression at Wk52. Similar results were obtained in pts treated with CZP + non-MTX DMARDs and with CZP monotherapy. This lower probability of remission at Wk52 in NR at Wk12 was consistently observed regardless of BL CRP, DAS28 and disease duration in both studies. Conclusions These analyses suggest that DAS28 response at Wk12 predicts long-term clinical and structural outcomes regardless of concomitant medication or BL disease status in Japanese pts treated with CZP. References Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest H. Yamanaka Grant/research support from: Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, UCB Pharma, Consultant for: Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, UCB Pharma, K. Yamamoto Grant/research support from: Pfizer, Abbott, Santen, Mitsubishi-Tanabe, Eisai, UCB Pharma, Consultant for: Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe, Eisai, UCB Pharma, T. Takeuchi Grant/research support from: Abbott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda, Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe, Asahi Kasei, Speakers bureau: Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, N. Ishiguro Grant/research support from: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Speakers bureau: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Taisho-Toyama, Otsuka, Y. Tanaka Grant/research support from: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbott, Eisai, Janssen, Speakers bureau: Mitsubishi-Tanabe, Abbott, Eisai, Chugai, Janssen, Santen, Pfizer, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Otsuka, Actelion, Eli Lilly, Nippon Kayaku, Quintiles Transnational, Ono, UCB Pharma, K. Eguchi Consultant for: UCB Pharma, A. Watanabe Grant/research support from: Astellas, Daiichi-Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical, Meiji Seika, Speakers bureau: Abbott, MSD, Otsuka, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe, Toyama Chemical, Bayer, Pfizer, H. Origasa Consultant for: Astellas, UCB Pharma, T. Shoji Employee of: UCB Pharma, S. Onodera Employee of: UCB Pharma, N. Miyasaka Grant/research support from: Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai, Astellas, T. Koike Speakers bureau: Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin, Daiichi-Sankyo, UCB Pharma
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A231-A231. DOI:10.1136/annrheumdis-2013-eular.727 · 10.38 Impact Factor

Publication Stats

3k Citations
558.75 Total Impact Points

Institutions

  • 2007–2015
    • University of Toyama
      • • Department of Neurosurgery
      • • Faculty of Medicine
      Тояма, Toyama, Japan
    • Sakakibara Heart Institute
      Фучу, Tōkyō, Japan
    • Saito Yukoukai Hospital
      Ōsaka, Ōsaka, Japan
  • 2007–2014
    • Toyama University
      Тояма, Toyama, Japan
  • 2009
    • University Hospital Medical Information Network
      Edo, Tōkyō, 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
    • Osaka Police Hospital
      Ōsaka, Ōsaka, Japan