Eisuke Inoue

National Center for Child Health and Development, Edo, Tokyo, Japan

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Publications (109)543.14 Total impact

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    ABSTRACT: Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality.Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ.Results The combined registry cohorts included 57 251 patients with RA (23
    No preview · Article · Feb 2016 · Annals of the Rheumatic Diseases
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    ABSTRACT: Objectives: To investigate the efficacy and safety of etanercept (ETN) in patients with rheumatoid arthritis (RA) with moderate disease activity and the possibility to discontinue ETN after achieving remission. Methods: Multicenter, randomized, and open-label study was conducted in Japan and Korea. RA patients (disease duration <5 years) with moderate disease activity despite methotrexate (MTX) treatment were allocated to either MTX or ETN + MTX (Period 1) for 12 months. Patients who achieved sustained remission defined as DAS28 < 2.6 at both 6 and 12 months in the ETN + MTX group, were randomized to either continue or discontinue ETN for 12 months (Period 2). Results: A total of 222 patients were enrolled in Period 1 and clinical remission was achieved in 106/157 (67.5%) and 5/28 (17.9%) patients in the ETN + MTX and MTX groups, respectively. In Period 2, sixty-seven patients were randomized and finally 28/32 (87.5%) and 15/28 (53.6%) patients who continued or discontinued ETN maintained clinical remission. Baseline disease activity and the presence of comorbid diseases influenced the maintenance of remission after ETN discontinuation. Conclusions: ETN + MTX was efficient for RA patients with moderate disease activity into remission. After achieving sustained remission, a half of the patients who discontinued ETN could maintain remission for 1 year.
    No preview · Article · Dec 2015 · Modern Rheumatology
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    ABSTRACT: Background: The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods: Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results: There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion: In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
    No preview · Article · Nov 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: To advance the treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), randomised controlled therapeutic studies with appropriate and sensitive outcomes are reuired. One candidate outcome is the 10-metre walk test (10MWT), a patient-centred, simple and functional measure. To calculate sample size based on 10MWT as the primary outcome, variability within and between subjects must be known. Data on 10MWT from 76 patients with HAM/TSP were prospectively collected from four specialist centres in Brazil, Japan, USA and UK. Data, collected at two time points, 6 months apart, were log transformed and subjected to analysis of covariance. Baseline mean (standard deviation = SD), median 10MWT were 23.5 (18.9), 16.3 s/10 m and at 6 months 24.9 (23.9), 16.4 s/10 m. The mean (SD) % increase in walk time was 5.74 % (28.2 %). After logarithmic transformation, the linear correlation between baseline and 24 weeks 10MWT was r = 0.938. Using these data, it was determined that a randomised controlled trial with 30 participants per group would have 90 % power to detect a 19 % decrease or a 23 % increase in 10MWT. The intra-patient variability of 10MWT is relatively small in HAM/TSP over 6 months. 10MWT is a feasible outcome measure for a clinical trial in HAM/TSP. To our knowledge, this is the first ever recommendation for the sample size required for trials in HAM/TSP patients.
    Full-text · Article · Oct 2015
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    Preview · Article · Aug 2015 · Retrovirology
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    ABSTRACT: Background: It has been reported that cyclosporine A (CYA) treatment may benefit idiopathic pulmonary fibrosis (IPF) patients. We conducted a randomized, controlled trial at 27 centers across Japan to evaluate the efficacy and safety of CYA with low-dose corticosteroids (CS) for IPF treatment. We compared these findings with others obtained using cyclophosphamide (CPA) combined with low-dose CS: the current standard therapy for IPF. Methods: The study involved patients between 50 and 74 years of age with well-defined IPF. The primary endpoint was a change in forced vital capacity (FVC) between baseline and 48 weeks. Results: We started this trial in May 2005 and ended it in December 2008. Ninety-nine patients were enrolled in the study. There was no significant difference between the CYA and CPA groups with regard to the change in FVC between baseline and 48 weeks (-0.078. L and -0.087. L, respectively). Neither did the two groups differ significantly with regard to the incidence rates of several adverse events. Conclusions: This clinical trial revealed no significant differences between the CYA group and the CPA group with regard to either safety data or the primary endpoint. However, the trial should be regarded as inconclusive because of its small sample size. There was a trend toward a reduction in FVC decline per year when the trial groups were compared with the placebo groups of previous studies, despite patients in this study having severely impaired lung function. Both therapies were well tolerated and lacked serious adverse effects.
    No preview · Article · Jul 2015 · Respiratory Investigation
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    ABSTRACT: Along with the advances of newly developed medical therapies in rheumatoid arthritis (RA), the number of pharmacoeconomical issues has been paid attention rapidly. For cost-utility analysis and determination of quality-adjusted life years, measurement of the EuroQol 5-dimensional descriptive system (EQ-5D) is essential, and has been used in several clinical studies. However, EQ-5D utility measure in Japanese patients with RA, especially in daily practice has not been fully documented. We analyzed the distribution of EQ5D utility scores and investigated the relationship between other clinical measures based on our IORRA database. Among 5,284 outpatients who participated in the IORRA cohort study on October 2007, data from 5,043 patients who completed the EQ-5D questionnaire were cross-sectionally analyzed. EQ-5D scores in each subgroup for baseline feature such as gender, age, disease activity score 28 (DAS28), and Japanese version of health assessment questionnaire (J-HAQ) were evaluated. For the evaluation of variables that influenced EQ-5D score, the contribution of each variable was evaluated by ANOVA. Average EQ-5D score was 0.76 in 5,284 patients (84% females, average age: 59.0 years, average disease duration: 12.4 years) whose average DAS28 of 3.3 and average J-HAQ of 0.74. EQ-5D scores were highly correlated with J-HAQ and DAS28, and were significantly lower in females and rheumatoid factor -positive patients. Older age, longer disease duration, higher DAS28, and higher J-HAQ were also significantly associated with lower EQ-5D scores. In multivariate analysis, the factor that most strongly influenced EQ-5D was J-HAQ (57.6%), followed by pain visual analog score (VAS; 12.5%). This study clearly demonstrated the distribution of EQ-5D score in the daily practice of RA patients, and provide important information for the pharmacoeconomical studies in rheumatology.
    No preview · Article · Jun 2015 · Modern Rheumatology
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    ABSTRACT: Background While the results of several observational studies suggest that light-to-moderate alcohol consumption may decrease the risk for susceptibility to or severity of rheumatoid arthritis (RA) (1-3), the findings regarding alcohol's effect on RA disease activity have been inconsistent. Although alcohol consumption in the Japanese general population was lower than that in European countries according to the 2011 World Health Organization's Global Status Report on Alcohol and Health, there are few reports on alcohol consumption in Japanese RA patients. Objectives To examine the relationship between alcohol consumption and disease activity in RA patients using the large observational cohort, IORRA. Methods Subjects were RA patients who participated in the IORRA study for the first time between October 2007 and October 2012. Patients were divided into 6 groups by alcohol-drinking status at baseline: the non-drinking group, the past-drinking group, drinking group 1 (0 g < amount of drinking per day [Alco-drink] 14 g), drinking group 2 (14 g < Alco-drink 28 g), drinking group 3 (28 g < Alco-drink 50 g), and drinking group 4 (50 g < Alco-drink). Multiple regression analyses were used to examine the relationship between alcohol consumption and baseline DAS28 or change in DAS28 from baseline to 1 year. Results Data from 2,369 patients (female: 83.6%, mean age: 54.6 years old, mean disease duration: 5.6 years, and mean DAS28: 3.5) were analyzed. The number of patients and their characteristics (% female, mean age, mean disease duration, mean DAS28 at baseline/after 1 year) in the non-drinking group, the past-drinking group, and drinking groups 1, 2, 3, and 4 were 1,436 (90.5%, 55.6 years old, 6.0 years, 3.6/2.9), 294 (83.3%, 53.7 years old, 4.7 years, 3.9/2.8), 263 (79.5%, 50.6 years old, 5.6 years, 3.3/2.6), 124 (66.1%, 53.6 years old, 3.6 years, 3.2/2.5), 111 (58.6%, 57.4 years old, 5.0 years, 3.4/2.8), and 114 (49.1%, 51.4 years old, 4.5 years, 3.3/2.6), respectively. Multivariate regression analysis confirmed that the baseline DAS28 in the past-drinking group (p<0.001) was significantly higher than that in the non-drinking group after adjusting for age, gender, RA disease duration and body mass index (BMI), whereas the baseline DAS28 in drinking group 1 (p=0.04) and group 2 (p=0.01) was significantly lower than that in the non-drinking group after adjusting for the same variables. There was no association between alcohol-drinking status and the change in DAS28 from baseline to 1 year after adjusting for age, gender, RA disease duration, BMI and DAS28 at baseline. Conclusions Although light alcohol consumption was associated with lower baseline DAS28 in RA patients, alcohol-drinking status was not associated with response to RA treatment. References Disclosure of Interest Y. Shimizu: None declared, K. Shidara: None declared, E. Tanaka: None declared, E. Inoue: None declared, R. Yamaguchi: None declared, N. Sugimoto: None declared, D. Hoshi: None declared, A. Nakajima: None declared, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda., A. Taniguchi Grant/research support from: Takeda., Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin., H. Yamanaka Grant/research support from: 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., Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, UCB.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Maintenance of remission is an important therapeutic goal in rheumatoid arthritis (RA). Several studies have proposed that RA patients maintaining remission could alter their current RA treatment strategy by reducing or withdrawing biological therapy1)2). However, few studies have investigated what factors lead to the loss of remission in a short period of time in RA patients who had previously sustained a remission state. Objectives To investigate the risk factors for early deterioration after sustained DAS28 remission in RA patients in daily practice by using the large, observational, Institute Of Rheumatology, Rheumatoid Arthritis (IORRA) cohort, in which data were collected biannually. Methods RA patients were selected for this study if they were not in DAS28 remission between October 2008 and October 2009 but subsequently achieved and sustained DAS28 remission at two consecutive data collections. These patients were observed to determine if DAS28 remission was maintained for 3 years. Cox regression analyses were conducted to examine risk factors for early deterioration within 3 years after sustained DAS28 remission at two consecutive data collections (1-year DAS28 remission). Results A total of 841 patients with a sustained 1-year DAS28 remission state were analyzed. Females comprised 83% of the study population. The mean (SD) age and disease duration were 57.3 (13.0) years and 11.9 (8.8) years, respectively. The mean (SD) DAS28 and Japanese version of the Health Assessment Questionnaire (J-HAQ) score were 2.1 (0.4) and 0.4 (0.5), respectively. The mean (SD) methotrexate dosage and percentage of biologic use was 8.4 (3.3) mg/week and 18%, respectively. The proportions of the patients whose disease activity deteriorated within 1, 2 or 3 years after a sustained 1-year DAS28 remission state were 41.4%, 57.0% and 64.4%, respectively. Cox regression analyses confirmed that longer disease duration (p=0.045), higher DAS28 score during a 1-year DAS28 remission (p<0.0001), and decrease in methotrexate dose during the DAS28 remission state (p=0.03) were the significant factors associated with early deterioration from the DAS28 remission state. Conclusions A decrease in the methotrexate dose during DAS28 remission was a significant factor associated with early deterioration in patients with RA in daily practice. Methotrexate dose reductions should be done prudently even in patients with sustained DAS28 remission. References Disclosure of Interest K. Shidara: None declared, E. Inoue: None declared, E. Tanaka: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, D. Hoshi: None declared, N. Sugimoto: None declared, A. Nakajima: None declared, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda, A. Taniguchi Grant/research support from: Takeda, Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin, H. Yamanaka Grant/research support from: 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, Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, UCB
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background The overall incidence of malignancies in patients with rheumatoid arthritis (RA) has been reported to be comparable or slightly higher than that in general population, whereas the increased incidence of malignant lymphoma has been reported to be consistent in most studies, including our previous report.1-3 However, the impact of expand use of methotrexate (MTX) and biological agents on the incidence of malignancies has not been thoroughly examined. Objectives To examine the incidence of malignancies in a large observational cohort of Japanese patients with RA over a long-term period. Methods The Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort is a large, single institute-based, observational cohort of RA patients established at our institute in 2000. All malignancies were extracted from the biannual self-reports of Japanese RA patients enrolled in the IORRA cohort from 2000 to 2013 and confirmed by their medical records. Patients with RA who dropped out of the IORRA were asked about comorbidities including malignancies by follow-up mail. For the overall malignancies and malignancies at each site, the standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated according to the data from the general Japanese population. Results Data from 11,106 patients with RA (1,992 males; 9,114 females), including 122,706 person-years (19,597 males; 103,109 females), were analysed. Percentages of MTX and biologics user increased from 34.2% and 0% in 2000, respectively, to 77.5% and 19.8% in 2013, respectively, in the IORRA. A total of 830 overall malignancies were confirmed (676.4 malignancies/100,000 person-years, SIR 0.96, 95% CI 0.90-1.03). Malignant lymphoma and lung cancer were the most frequent types of malignancy (114 cases each). A significant increase in the SIR was identified for malignant lymphoma in both males (SIR 4.62, 95% CI 3.04-6.72) and females (SIR 5.27, 95% CI 4.22-6.50) and for lung cancer in males (SIR 1.36, 95% CI 1.03-1.75). A significant decrease in the SIR was identified for gastric cancer in both males (SIR 0.58, 95% CI 0.39-0.82) and females (SIR 0.77, 95% CI 0.60-0.99) and for colorectal cancer in both males (SIR 0.53, 95% CI 0.35-0.78) and females (SIR 0.56, 95% CI 0.43-0.71). Conclusions No significant difference in the overall incidence of malignancies in Japanese patients with RA was noted compared with the general Japanese population regardless of the expand use of MTX and biological agents in this period. However, there was a significant difference in the sites of the malignancies. A marked significant increase in the incidence of malignant lymphoma in both males and females was observed. References Disclosure of Interest N. Sugimoto: None declared, E. Tanaka: None declared, E. Inoue: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, A. Kobayashi: None declared, K. Shidara: None declared, D. Hoshi: None declared, A. Nakajima: None declared, A. Taniguchi Grant/research support from: Takeda, Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda, H. Yamanaka Grant/research support from: 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, Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, UCB
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Rheumatoid arthritis (RA) reduces functional ability and quality of life. Comorbidities may have considerable impact on physical function, and functional disability consistently increases with higher levels of comorbidity, irrespective of RA disease activity (1). We reported that patients with many comorbidities were treated less frequently with methotrexate (MTX) and biologics and tended to exhibit corticosteroid dependency, resulting in worse physical function (2); however, the effects of different comorbidities on treatment strategy and subsequent outcomes, such as disease activity and physical function, have not been evaluated. Objectives To assess disease activity, functional impairment and treatment in Japanese RA patients with comorbidities in daily practice. Methods Among the patients who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) study in October 2013, we extracted those who answered “yes” to the question, “Have you ever had or do you currently have any of the following diseases?”, and cross-sectionally assessed patient characteristics, disease activity, functional impairment and treatment by comorbidity: (1) angina pectoris/myocardial infarction (coronary artery disease [CAD]), (2) cerebral hemorrhage/cerebral infarction/subarachnoid hemorrhage (stroke), (3) hypertension, (4) heart failure, (5) interstitial pneumonia (IP), (6) pulmonary emphysema/chronic bronchitis/asthma/bronchiectasis (chronic obstructive pulmonary disease [COPD]), (7) gastric ulcer/duodenal ulcer/gastrointestinal hemorrhage (GI), (8) hepatic dysfunction/viral hepatitis, (9) cancer, (10) depression, (11) diabetes, (12) fracture. Results The study included 5,837 patients with RA (mean age, 60.9 y; RA duration, 14.8 y; females, 85.5%; DAS28, 2.6; Japanese version of the HAQ [J-HAQ] score, 0.59; percentage of patients receiving MTX/corticosteroid/biologics, 77.4%/33.2%/18.8%). The most common comorbidity was hypertension (19.3%), followed by COPD (4.7%), GI (4.5%), diabetes (4.4%), fracture (4.0%) and IP (2.8%). The mean age was highest in patients with CAD (71.6 y) and lowest in those with depression (58.1 y). The mean DAS28 was below 3.0, except in patients with IP (3.2) and cancer (3.0), whereas all comorbidities except hypertension and diabetes (0.78) had a J-HAQ score of 0.8 or more; in particular, fracture (1.04) and IP (1.01) were associated with more advanced functional impairment. The percentage of patients receiving MTX was lowest for IP (47.6%) and heart failure (55.3%) and highest for depression (77.3%). The percentage of patients receiving corticosteroids was highest for IP (68.1%) and lowest for diabetes (36.3%). The percentage of patients receiving biologics was highest for IP (25.9%) and depression (21.8%), and lowest for cancer (12.5%). Conclusions Although the choice of RA therapy varies among different comorbidities, current RA therapy provides adequate control to achieve low disease activity or remission in most patients. However, progression of functional impairment cannot be avoided in the presence of comorbidities, suggesting the importance of prevention and treatment of comorbidities, in addition to the control of RA disease activity. References Disclosure of Interest E. Tanaka: None declared, E. Inoue: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, N. Sugimoto: None declared, D. Hoshi: None declared, K. Shidara: None declared, E. Sato: None declared, Y. Seto: None declared, A. Nakajima: None declared, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda., A. Taniguchi Grant/research support from: Takeda., Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin., H. Yamanaka Grant/research support from: AbbVie, Asahikasei Pharma, Astellas, Bristol-Myers-Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taisho-Toyama, Takeda, and Teijin Pharma., Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, and UCB.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Indirect costs of rheumatoid arthritis (RA) due to losses such as reduced productivity are an important social issue in addition to rapidly increasing direct costs; however, indirect costs have not been thoroughly assessed in Japan. With the recent changes in socioeconomic structure, the number of female paid workers has been increasing; thus, the impact of RA on the work impairment of Japanese patients has been rapidly increasing. Furthermore, work status is strongly influenced by cultural differences among races. Longitudinal analyses of factors contributing to the worsening of work impairment should be conducted in patients with RA in real-world settings. Objectives To identify factors contributing to early worsening of absenteeism in patients with RA in daily practice. Methods The study population consisted of patients with RA who were working for pay and who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study in 2012 to 2013, had an absenteeism score of 0 as determined by the Work Productivity and Activity Impairment (WPAI) questionnaire at baseline, and could be followed up for WPAI assessments for at least 6 months to a maximum of 18 months. The time to 10% or more absenteeism (percent work time missed due to RA) was the primary outcome. A Cox regression analysis was used to identify factors contributing to the worsening of absenteeism. Results The study included 1,941 patients with RA (mean age, 50.6 years; RA duration, 10.8 years; females, 79.3%; DAS28, 2.6; Japanese version of the Health Assessment Questionnaire [J-HAQ], 0.32). Absenteeism first exceeded 10% at 6, 12 and 18 months in 47 (cumulative probability of worsening: 2.4% [95% CI: 1.7%>3.1%]), 33 (4.5% [95% CI: 3.5%>5.4%]) and 20 (6.2% [95% CI: 5.0%>7.4%]) patients, respectively. Results of a multivariate Cox regression analysis showed that lower EQ-5D scores at baseline (p=0.01) and steroid dosage at baseline (p=0.01) were significantly associated with earlier worsening of absenteeism, and that the use of biologics did not have a significant impact (p=0.46). Conclusions Factors contributing to earlier worsening of absenteeism were identified in patients with RA in daily practice. The results suggest that preventing quality of life deterioration without steroid use might be important in stopping the progression of work impairment. Disclosure of Interest E. Tanaka: None declared, E. Inoue: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, N. Sugimoto: None declared, D. Hoshi: None declared, K. Shidara: None declared, E. Sato: None declared, Y. Seto: None declared, A. Nakajima: None declared, S. Momohara Consultant for: AbbVie, Bristol-Myers-Squibb, Eisai, Mitsubishi-Tanabe, and Takeda., A. Taniguchi Grant/research support from: Takeda., Consultant for: AbbVie, Eisai, Mitsubishi-Tanabe, and Teijin., H. Yamanaka Grant/research support from: AbbVie, Asahikasei Pharma, Astellas, Bristol-Myers-Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taisho-Toyama, Takeda, and Teijin Pharma., Consultant for: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Nihon-Kayaku, Mitsubishi-Tanabe, Pfizer, Takeda, and UCB.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: The aim of this study was to evaluate the associations between potential risk factors and the occurrence of established vertebral fractures in Japanese patients with rheumatoid arthritis (RA). A total of 10,469 patients with RA were enrolled in a prospective, observational study from 2000 to 2011. Self-reported vertebral fractures were verified using patient's medical records and radiographs. Cox proportional hazards models were used to analyze independent contributions of various risk factors for established vertebral fracture occurrence. During a mean follow-up of 5.8 years, established vertebral fractures in 170 patients were verified with medical records and radiographs. Multivariate Cox regression analyses estimated that the hazards ratios of sustaining vertebral fractures increased by 1.84 for female gender, 1.72 for every 10 years of increased age, 1.26 for Disease Activity Score in 28 joints (DAS28), 1.44 for Japanese Health Assessment Questionnaire-Disability Index (J-HAQ-DI), 2.21 for history of any previous fractures, and 1.09 for daily prednisolone dose (mg/day). We confirmed the associations between vertebral fractures and advanced age, J-HAQ-DI, and high daily prednisolone dose; and found significant correlations between vertebral fractures and female gender, DAS28, and history of any previous fracture in Japanese RA patients.
    No preview · Article · Mar 2015 · Modern Rheumatology
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    ABSTRACT: To analyze sex difference in the effect of smoking on remission proportions in patients with rheumatoid arthritis (RA). Subjects were Japanese patients with RA who participated in the IORRA survey conducted in April 2011 and reported smoking status. Clinical characteristics, treatment status, and the percentages achieving remission were compared between subjects stratified by sex and smoking status. To confirm the differential effects of sex and smoking status on remission, we used multivariate logistic regression models with the dependent variable as 28-joint Disease Activity Score (DAS28) remission. Among 810 men and 4206 women, 162 (20.0%) and 3173 (75.4%), respectively, were never smokers; 208 (25.7%) and 314 (7.5%), respectively, were current smokers. In men, never smokers tended to have higher remission proportions than past and current smokers. In contrast, smoking status seemed not to affect remission in women. Except for lower corticosteroid dose in male never smokers, no significant differences were observed in comparing treatment status. By multivariate analyses, male past and current smokers were negatively associated with DAS28-erythrocyte sedimentation rate remission compared to male never smokers [OR 0.66 and 0.61, 95% CI (0.44-0.98) and (0.39-0.96), respectively]. However, female past and current smokers were not associated with remission compared to female never smokers [OR 1.04 and 1.19, 95% CI (0.86-1.25) and (0.91-1.54), respectively]. We demonstrated that the effect of smoking on remission proportions differed between men and women. Our findings suggest that both sex and smoking status are important considerations when planning a treatment strategy for patients with RA.
    No preview · Article · Mar 2015 · The Journal of Rheumatology
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    ABSTRACT: Objective: To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA). Methods: By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster. Results: A total of 7,986 patients (female 83.1%) accumulated 30,140 patient-years of observation, and 366 events were confirmed. The standardized incidence rate per 1,000 patient-years was 9.1 (95% confidence interval (CI) 6.2-12.9) in total, 7.8 (3.6-14.8) in men, and 10.3 (6.8-15.0) in women. The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1.268, 95% CI 1.153-1.393, p < 0.0001), high disease activity compared with remission (HR 1.642, 95% CI 1.067-2.528, p < 0.05), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1.531, 95% CI 1.211-1.936, p < 0.001; ≥ 5 mg/day compared with 0 mg/day: HR 1.471, 95% CI 1.034-2.093, p < 0.05), and methotrexate (HR 1.382, 95% CI 1.076-1.774, p < 0.05). Conclusion: This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.
    No preview · Article · Feb 2015 · Modern Rheumatology
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    ABSTRACT: Background/purpose: The use of biologic disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) has been increasing since 2003. In this study, we evaluated changes in the characteristics of patients receiving biologic DMARDs daily, in Japan. Methods: The characteristics of all RA patients who received any biologic DMARD at the Institute of Rheumatology, Tokyo Women's Medical University, within 1 year after its approval in Japan, were retrospectively evaluated. The periods of patient enrollment for each biologic agent were: infliximab (IFX), 2003-2004; etanercept (ETN), 2005-2006; tocilizumab (TCZ), 2008-2009; adalimumab (ADA), 2008-2009; abatacept (ABT), 2010-2011; and golimumab (GLM), 2011-2012. We retrospectively collected individual patient characteristics, concomitant medication usage, and disease activity assessed by disease activity score 28 (DAS28) at the time of administration, from the medical records. The retention rate for each agent at 6 months after treatment initiation was also assessed. Results: The numbers of patients who received each biologic DMARD at our institute within 1 year after its approval were: IFX, 49; ETN, 50; TCZ, 62; ADA, 52; ABT, 40; and GLM, 77. From 2003 to 2012, the proportion of patients with prior use of any biologic DMARD increased, as did concomitant use and dose of methotrexate (MTX); however, corticosteroid use and doses decreased. DAS28, at the time of treatment initiation, gradually decreased. At the time of IFX administration, 75% and 25% of patients had high and moderate disease activity respectively, compared to 25% and 58% respectively, of patients who received GLM. No significant difference was observed in the retention rate of biologic DMARDs at 6 months (range, 75.0% to 89.6%). Conclusion: Baseline disease activity of RA patients who received biologic DMARDs between 2003 and 2012 has changed from high to moderate in daily practice in Japan.
    No preview · Article · Jan 2015 · Modern Rheumatology
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    ABSTRACT: Objectives: To evaluate the cost-effectiveness of tocilizumab in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. Methods: The cost-effectiveness was determined using a Markov model-based probabilistic simulation. Data from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study between April 2007 and April 2011 were extracted using a pair-matching method: tocilizumab group (n = 104), patients who used at least 1 disease-modifying anti- rheumatic drug and in whom tocilizumab treatment was initiated; methotrexate group (n = 104), patients in whom methotrexate treatment was initiated for the first time or after an interruption of 6 or more months. Assuming a 6-month cycle length, health benefits and costs were measured over a lifetime and discounted at an annual rate of 3%. Results: Compared with methotrexate treatment, lifetime costs and quality-adjusted life years (QALYs) for tocilizumab treatment were approximately 1.5- and 1.3-times higher, respectively. Incremental cost per QALY gained with tocilizumab was $49,359, which was below the assumed cost-effectiveness threshold of $50,000 per QALY. The probability of tocilizumab being cost- effective was 62.2%. Conclusion: The simulation model using real-world data from Japan showed that tocilizumab (at a certain price) may improve treatment cost-effectiveness in patients with moderate-to-severe RA by enhancing quality-adjusted life expectancy.
    No preview · Article · Dec 2014 · Modern Rheumatology
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    ABSTRACT: Objectives: To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. Methods: We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. Results: We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. Conclusions: Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice.
    No preview · Article · Dec 2014 · Modern Rheumatology
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    ABSTRACT: Despite improvements in rheumatoid arthritis disease activity of in the past 10 years, the incidence of self-reported non-vertebral fractures did not decrease in our cohort of 9,987 patients. This study may indicate that osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the rheumatoid arthritis disease activity.
    No preview · Article · Oct 2014 · Osteoporosis International
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    ABSTRACT: To clarify the impact of comorbidities on treatment strategies and outcomes in patients with rheumatoid arthritis (RA) using a large observational RA cohort, the presence of comorbidities was assessed using the Charlson Comorbidity Index (CCI). Changes in medication, disease activity by Disease Activity Score-28 joint count (DAS28) over 6 months, disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), and quality of life by EuroQOL-5-Dimensions (EQ-5D) over 1 year in patients with high disease activity (DAS28 > 5.1) at baseline were assessed according to age-adjusted CCI (CCIA) and categorized into four groups (CCIA 0, 1-2, 3-4, and ≥5). Among 5,317 patients, 975 patients (18.3 %) had at least one comorbidity listed by CCI. DAS28, J-HAQ, and EQ-5D increased in severity with increased CCIA levels. Among patients with high disease activity (n = 267), treatment with methotrexate and/or biologics and improved DAS28 scores, shown by attenuated intensity, were associated with increased CCIA levels. J-HAQ improved from 1.29 ± 0.31 to 0.87 ± 0.37 in 1 year in the CCIA 0 group. The adjusted difference (standard error) in J-HAQ at 1 year in CCIA 1-2, 3-4, and ≥5 groups was worse than J-HAQ in the CCIA 0 group by 0.32 (0.09, p < 0.001), 0.45 (0.10, p < 0.001), and 0.45 (0.15, p < 0.01), respectively. The magnitude of improvement of EQ-5D was significantly attenuated with increasing CCIA levels. Thus, patients with comorbidities may not experience the same degree of benefit from recent RA treatments compared with patients without comorbidities in daily practice.
    Full-text · Article · Jul 2014 · Clinical Rheumatology

Publication Stats

2k Citations
543.14 Total Impact Points

Institutions

  • 2015
    • National Center for Child Health and Development
      Edo, Tokyo, Japan
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 2003-2015
    • Tokyo Women's Medical University
      • • Institute of Rheumatology
      • • Department of Orthopedic Surgery
      Edo, Tōkyō, Japan
  • 2012-2014
    • Kitasato University
      Edo, Tōkyō, Japan