Showing papers by "Shigeki Momohara published in 2013"

Genome-wide association study and gene expression analysis identifies CD84 as a predictor of response to etanercept therapy in rheumatoid arthritis

Abstract: Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to antiTNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n=733), infliximab (n=894), or adalimumab (n=1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (DDAS) in the etanercept subset of patients (P=8610 28 ), but not in the infliximab or adalimumab subsets (P.0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 39 UTR of an immune-related gene,CD84, and thealleleassociated withbetterresponsetoetanerceptwas associatedwithhigherCD84 gene expression in peripheral blood mononuclear cells (P=1610 211 in 228 non-RA patients and P=0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P=0.02, n=210) and showed a non-significant trend for better DDAS in a subset of RA patients with gene expression data (n=31, etanercepttreated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA

Estimates of the prevalence of and current treatment practices for rheumatoid arthritis in Japan using reimbursement data from health insurance societies and the IORRA cohort (I)

Abstract: The prevalence of rheumatoid arthritis (RA) and its current treatment practices in Japan are poorly documented. Therefore, we examined these factors in a Japanese health insurance database. We analyzed reimbursement data provided by health insurance societies for 1 million individuals, including healthy individuals, registered from January 2005 to June 2011. Changes in treatments were determined in 320 thousand individuals originally registered in 2005. The treatment patterns were compared with those of the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort managed by Tokyo Women’s Medical University. The estimated prevalence of RA was 1.24 million (1.0 % of the Japanese population), excluding suspected cases, and 706 thousand (0.6 %) in a sensitivity analysis. Seventy-nine percent of patients were treated for RA. Methotrexate was used by 27 % of patients. In 2005, 5 % of patients were prescribed methotrexate at >8 mg/week, which increased to 13 % in 2011. These rates were lower than those in the IORRA cohort. Our results indicate that the prevalence of RA in Japan is somewhere between 0.6 and 1.0 %. Considering that methotrexate is infrequently used, the implementation of aggressive treatment regimens such as the ‘Treat to Target’ strategy is important to achieve tight control of RA in Japan.

Management of rheumatoid arthritis: the 2012 perspective

Abstract: Management of rheumatoid arthritis (RA) has improved over the last 10 years. These changes have been monitored in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) observational cohort, and clinical remission has become a realistic goal. However, we should recognize that the ultimate goal of treatment is to improve long-term outcomes. These improvements have been achieved not only by new drugs, but also by the overall approach toward treating patients. Biologics in RA have been successful; however, safety concerns and pharmacoeconomical issues are still debated. Protein kinase inhibitors have been developed, and can be called “molecular-targeting antirheumatic drugs” (MTARDs), as opposed to “disease-modifying antirheumatic drugs.” In comparison with biologics, oral MTARDs should be less expensive; however, their safety profile should be confirmed. Considering the limitations of randomized trials, it is encouraged to conduct studies based on daily practice. It is time to consider the application of the evidence generated from “our” patients to patients in daily practice, namely institute-based medicine as opposed to evidence-based medicine, of which “IORRA-based medicine” would be representative. Finally, there remains much for us rheumatologists to do for our patients, including patient-perspective approaches.

Analysis of perioperative clinical features and complications after orthopaedic surgery in rheumatoid arthritis patients treated with tocilizumab in a real-world setting: results from the multicentre TOcilizumab in Perioperative Period (TOPP) study

Abstract: Objective To evaluate perioperative changes in rheumatoid arthritis (RA) patients treated with tocilizumab.

PADI4 and HLA-DRB1 are genetic risks for radiographic progression in RA patients, independent of ACPA status: results from the IORRA cohort study.

Abstract: Introduction Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease influenced by both genetic and environmental factors, leading to joint destruction and functional impairment. Recently, a large-scaled GWAS meta-analysis using more than 37,000 Japanese samples were conducted and 13 RA susceptibility loci were identified. However, it is not clear whether these loci have significant impact on joint destruction or not. This is the first study focused on the 13 loci to investigate independent genetic risk factors for radiographic progression in the first five years from onset of RA. Methods Sharp/van der Heijde score of hands at 5-year disease duration, which represents joint damage, were measured retrospectively and used as an outcome variable in 865 Japanese RA patients. Genetic factors regarded as putative risk factors were RA-susceptible polymorphisms identified by the Japanese GWAS meta-analysis, including HLA-DRB1 (shared epitope, SE), rs2240340 (PADI4), rs2230926 (TNFAIP3), rs3093024 (CCR6), rs11900673 (B3GNT2), rs2867461 (ANXA3), rs657075 (CSF2), rs12529514 (CD83), rs2233434 (NFKBIE), rs10821944 (ARID5B), rs3781913 (PDE2A-ARAP1), rs2841277 (PLD4) and rs2847297 (PTPN2). These putative genetic risk factors were assessed by a stepwise multiple regression analysis adjusted for possible non-genetic risk factors: autoantibody positivity (anti-citrullinated peptide antibody [ACPA] and rheumatoid factor), history of smoking, gender and age at disease onset. Results The number of SE alleles (P = 0.002) and risk alleles of peptidyl arginine deiminase type IV gene (PADI4, P = 0.04) had significant impact on progressive joint destruction, as well as following non-genetic factors: ACPA positive (P = 0.0006), female sex (P = 0.006) and younger age of onset (P = 0.02). Conclusions In the present study, we found that PADI4 risk allele and HLA-DRB1 shared epitope are independent genetic risks for radiographic progression in Japanese rheumatoid arthritis patients. The results of this study give important knowledge of the risks on progressive joint damage in RA patients.

Prevalence of and factors associated with vitamin D deficiency in 4,793 Japanese patients with rheumatoid arthritis

Abstract: To determine the prevalence of vitamin D deficiency and associations with clinical characteristics in Japanese patients with rheumatoid arthritis (RA), serum 25(OH)D levels, laboratory data, and clinical data were obtained from 4,793 patients with RA (4,075 women, 718 men, mean age 59.7 years) who participated in the Institute of Rheumatology Rheumatoid Arthritis observational cohort study in April and May of 2011. Serum vitamin D levels were evaluated using a radioimmunoassay. We defined vitamin D deficiency as <20 ng/mL and severe deficiency as <10 ng/mL. Associations of vitamin D deficiency with patient characteristics were examined using multivariate logistic regression. Among all patients, the mean (SD) serum 25(OH)D level was 16.9 ng/mL (6.1), and the prevalence of vitamin D deficiency and severe deficiency were 71.8 and 11.5 %, respectively. In multivariate analysis, female gender, younger age, high Japanese version of health assessment questionnaire (HAQ) disability score, low serum total protein levels, low serum total cholesterol levels, high serum alkaline phosphate (ALP) levels, and non-steroidal anti-inflammatory drug (NSAID) use were significantly associated with vitamin D deficiency (P < 0.01). Vitamin D deficiency appears to be common in Japanese patients with RA, as previously reported for patients of other ethnicities. Female gender, younger age, high HAQ disability score, low serum levels of total protein and total cholesterol, high serum ALP levels, and NSAID use appear to be associated with vitamin D deficiency in Japanese patients with RA.

Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis: a prospective observational cohort study

Abstract: Summary Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture.

Vaccination against seasonal influenza is effective in Japanese patients with rheumatoid arthritis enrolled in a large observational cohort

Abstract: Objective: To investigate the effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA) from a large practice-based cohort.Method: Patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires as part of the April IORRA surveys of 2001, 2002, 2003, and 2007, which included their influenza vaccination status and occurrence of an actual influenza attack. Vaccine coverage rate and attack rates were calculated in each season. Relative risks (RRs) of vaccination for an actual influenza attack were evaluated and risk factors for influenza infection were determined by multiple logistic regression analysis.Results: Data from 3529, 4518, 4816, and 4872 patients in the 2000/01, 2001/02, 2002/03, and 2006/07 seasons, respectively, were analysed. Coverage rates were increased from 12.2% in the 2000/01 season to 38.7% in the 2006/07 season. For each season, the attack rates in vaccinated patients trended lower than the...

Proximal rotational closing-wedge osteotomy of the first metatarsal in rheumatoid arthritis: clinical and radiographic evaluation of a continuous series of 35 cases

Abstract: Objectives The introduction of powerful antirheumatic drugs has dramatically improved the treatment of rheumatoid arthritis (RA), leading clinicians to reconsider the benefits of joint preservation for rheumatoid forefoot deformities. We have employed joint-preserving forefoot surgeries, including rotational closing-wedge osteotomy of the first metatarsal. The aim of our study is to assess the short-term results of this procedure.

Analysis of direct medical and nonmedical costs for care of rheumatoid arthritis patients using the large cohort database, IORRA

Abstract: Our goal was to determine the annual direct medical and nonmedical costs for the care of patients with rheumatoid arthritis (RA) using data from a large cohort database in Japan. Direct medical costs [out of pocket to hospitals and pharmacies and for complementary and alternative medicine (CAM)] and nonmedical costs (caregiving, transportation, self-help devices, house modifications) were determined for RA patients who were participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) studies conducted in October 2007 and April 2008. Correlations between these costs and RA disease activity, disability level, and quality of life (QOL) were assessed. Data were analyzed from 5,204 and 5,265 RA patients in October 2007 and April 2008, respectively. The annual direct medical costs were JPY132,000 [out of pocket to hospital (US$1 = JPY90 in 2007)], JPY84,000 (out of pocket to pharmacy), and JPY146,000 (CAM). Annual direct nonmedical costs were JPY105,000 (caregiving), JPY22,000 (transportation), JPY30,000 (self-help devices), and JPY188,000 (house modifications). Based on the utilization rate for each cost component, the annual medical and nonmedical costs for each RA patient were JPY262,136 and JPY61,441, respectively. Costs increased with increasing RA disease activity and disability level or worsening quality of life (QOL). Based on the IORRA database, patients with RA bear heavy economic burdens that increase as the disease is exacerbated. The results also suggest that the increase in medical and nonmedical costs may be ameliorated by the proactive control of disease activity.

Administration of teriparatide treatment for a challenging case of nonunion of periprosthetic fracture after total knee arthroplasty

Abstract: Management of a periprosthetic fracture after total knee arthroplasty is often challenging because it typically occurs in elderly patients, who often have osteoporotic bone with a high risk of delayed union and nonunion. Thus, administration of a medication that could effectively accelerate fracture healing to prevent a delayed union or nonunion should significantly improve treatment outcome and patient's quality of life. We report the case of a 74-year-old rheumatoid arthritis woman with nonunion of a periprosthetic fracture after total knee arthroplasty, in whom bone union could not be achieved even after she underwent internal fixation and bone grafting twice; however, successful bone fusion was achieved after simple once-weekly administration of teriparatide for 6 months. Although we report only one patient, the present case may suggest the advantage of preventive administration of teriparatide in addition to surgical procedures for treating nonunion of a periprosthetic fracture after total knee arthroplasty.

Major depressive disorder in patients with rheumatoid arthritis.

Abstract: To investigate the point prevalence of major depressive disorder (MDD) as diagnosed by the Mini-International Neuropsychiatric Interview (M.I.N.I) in patients with rheumatoid arthritis (RA) and to determine whether MDD is related to features of RA disease, such as disease activity or physical dysfunction. Of the patients with RA who participated in the IORRA survey conducted in October 2005, 162 were evaluated using the M.I.N.I., the Center for Epidemiologic Studies-Depression (CES-D) scale, and the two-question depression screen for MDD. RA clinical features were obtained from the concomitant IORRA cohort database. Relationships between MDD and RA disease features were analyzed by the Wilcoxon rank sum test and Pearson’s chi-square test. The point prevalence of MDD as diagnosed by the M.I.N.I. was 6.8 % in our Japanese patients with RA. The percentage of depressive patients was determined to be 23.5, 17.3, or 7.4 % according to the CES-D scale with cut-off points of 16, 19, or 27, respectively, and 14.2 % according to the two-question depression screen. The best cut-off point for CES-D for risk of MDD diagnosed by M.I.N.I. in this study was determined to be 23, with 11.7 % depressive patients having the highest sum of sensitivity and specificity. No relationship between MDD and RA disease activity was detected. By using the well-established structural interview instrument M.I.N.I., we determined the point prevalence of MDD in the RA patients enrolled in this study to be 6.8 %, leading to the conclusion that concomitant MDD does not seem to influence disease activity in RA patients.

Sites, frequencies, and causes of self-reported fractures in 9,720 rheumatoid arthritis patients: a large prospective observational cohort study in Japan

Abstract: Summary Sites, frequencies, and causes of self-reported fractures in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. The incidence and cause of fracture differ by anatomical site, sex, and age. These differences may be considered in establishing custom strategies for preventing fractures in RA patients in the future.

No increased mortality in patients with rheumatoid arthritis treated with biologics: results from the biologics register of six rheumatology institutes in Japan

Abstract: To investigate the influence of biologics on mortality and risk factors for death in rheumatoid arthritis (RA) patients. RA patients treated with at least one dose of biologics in daily practice in six large rheumatology institutes (“biologics cohort”) were observed until 15 May 2010 or death, whichever occurred first. Mortality of the biologics cohort and the “comparator cohort” (comprising patients among the IORRA cohort who had never been treated with biologics) was compared to that of the Japanese general population. Factors associated with mortality were assessed by a Cox model. Among 2683 patients with 6913.0 patient-years of observation, 38 deaths were identified in the biologics cohort. The probability of death in patients lost to follow-up, calculated using the weighted standardized mortality ratio (SMR), was 1.08 [95 % confidence interval (CI) 0.77–1.47] in the biologics cohort and 1.28 (95 % CI 1.17–1.41) in the comparator cohort. Pulmonary involvement was the main cause of death (47.4 %), and the disease-specific SMR of pneumonia was 4.19 (95 % CI 1.81–8.25). Risk factors for death included male gender [hazard ratio (HR) 2.78 (95 % CI 1.24–6.22)], advanced age (HR 1.07, 95 % CI 1.03–1.11), and corticosteroid dose (HR 1.08, 95 % CI 1.01–1.17). Mortality in RA patients exposed to biologics did not exceed that in patients not exposed to biologics, but death from pulmonary manifestations was proportionally increased in RA patients exposed to biologics.

An obliquely placed headless compression screw for distal interphalangeal joint arthrodesis.

Abstract: Purpose To assess the outcomes of our technique involving oblique headless compression screw for arthrodesis of the thumb interphalangeal joint and the distal interphalangeal joints of the other digits. Methods A total of 28 joints (19 thumb interphalangeal and 9 distal interphalangeal) in 23 patients with a mean age of 65 years (range, 58–74 y) were retrospectively analyzed. All operations were performed with the Acutrak2 micro-screw. After the resection of synovium and joint cartilage by a dorsal approach, a 0.88-mm diameter guide wire was inserted at the ulnar side of the proximal phalanx in the thumb and radial side of the middle phalanx in the other digits from proximal to distal to fix the joint obliquely. We verified its position under fluoroscopic control and placed the cannulated screw from proximal to distal over the guide wire. Results Intraoperative rigid fixation was obtained except for 1 case, which required additional K-wire fixation. The overall union rate was 96%. Average time to fusion was 11 weeks (range, 8–30 wk), with 76% achieving union within 3 months. There were 2 complications, 1 nonunion and 1 late infection. Other complications such as dorsal skin necrosis, nail deformity, and paresthesia did not occur. Conclusions Efforts to avoid invasion of the nailbed can be technically demanding. We believe that our proximal to distal technique with oblique placement of the headless compression screw is a straightforward and effective method with a relatively low risk of complication. Type of study/level of evidence Therapeutic IV.

Does mobile-bearing knee arthroplasty motion change with activity?

Abstract: Background The purpose of this study was to evaluate the effect of mobile-bearing implant design and activity on knee arthroplasty kinematics during three activities of daily living. Methods In vivo kinematics were analyzed using 3D model registration from fluoroscopic images of non-weightbearing knee flexion-extension, weight-bearing squatting and stair activities in 20 knees in 10 patients with bilateral total knee arthroplasty. Each patient had one rotating-platform and one meniscal-bearing variant of the same prosthesis design. Results Anteroposterior translations in meniscal-bearing knees were larger than those in rotating-platform knees for the different dynamic conditions. Meniscal-bearing knees showed more posterior femoral locations with activities that increased demand on the quadriceps. Condylar translations changed little in rotating-platform knees with different activities. Conclusions Activity dynamics can have a significant influence on knee kinematics, and have a greater effect on the kinematics of unconstrained meniscal-bearing prostheses than rotating-platform knee prostheses. Level of evidence Level II.

Functional disability can deteriorate despite suppression of disease activity in patients with rheumatoid arthritis: a large observational cohort study

Abstract: To analyze the relationship between the progression of disability and disease activity in patients with rheumatoid arthritis (RA) in daily practice. Patients from an observational cohort, IORRA, who completed surveys during 2009–2011 were eligible. Linear regression of disease activity score 28 (DAS28), Japanese version of Health Assessment Questionnaire (J-HAQ), and EQ-5D from baseline were calculated, and the angles of the regression lines were designated DAS28 slope, J-HAQ slope, and EQ-5D slope, respectively, in each patient; averages were compared between treatment groups. A total of 5,038 patients [84.0 % female, mean age 59.4 (SD 13.1) years, disease duration 13.2 (9.6) years, DAS28 3.29 (1.14), and J-HAQ 0.715 (0.760)] were analyzed. The average DAS28 slope indicated improvement in all groups, whereas J-HAQ slopes were negative in patients on methotrexate (MTX), biologics, combination biologics/disease-modifying antirheumatic drugs (DMARDs), and combination biologics/MTX at baseline, but positive in patients on prednisolone >5 mg/day [0.010 (0.153)] and not on MTX at baseline [0.007 (0.122)], representing a worsening of disability. There is some disparity between improvement of disease activity and progression of disability, suggesting that quality of remission must be considered.

Disability is the major negative predictor for achievement of Boolean-based remission in patients with rheumatoid arthritis treated with tocilizumab

Abstract: To analyze the efficacy of tocilizumab (TCZ) and the factors that influence achievement of Boolean-based remission in patients with rheumatoid arthritis (RA) treated with TCZ in daily clinical practice. The efficacy of TCZ at 24 weeks after initiation of TCZ in 80 patients with RA was analyzed by comparing achievement of “DAS28 remission” with that of “Boolean-based remission”. The predictive factors that influence achievement of Boolean-based remission were determined using multiple logistic regression analysis using a step-wise method. DAS28 remission and Boolean-based remission were achieved in 50.0 and 12.5 % of patients, respectively. Significant differences in achieving Boolean-based remission were observed when patients were stratified by disease duration in tertiles (p < 0.05) and by physical function in tertiles (p < 0.05); no such differences were observed for achieving DAS28 remission. The least achievable component among the Boolean-based remission criteria was patient’s global assessment. The predictive factor for not achieving Boolean-based remission at 24 weeks was having a worse baseline physical function (odds ratio, 3.66; 95 % confidence interval, 1.17–14.48). This study suggests that baseline disability predicts a lack of achievement of Boolean-based remission. Thus, better responses to TCZ may be obtained when TCZ is initiated in RA patients before disability develops.

Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadequate responses to methotrexate

Abstract: We aimed to assess the efficacy of tacrolimus (TAC) as an add-on therapy in patients with rheumatoid arthritis (RA) who were previously treated with methotrexate (MTX) but not with biologics. The study group (MTX + TAC group) consisted of 157 patients (selected from among the patients in the Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005 to October 2009) who received add-on therapy with TAC in addition to MTX, but without biologics. A propensity score (PS) for the use of TAC was derived, and 471 PS-matched patients who received MTX alone or MTX with other non-biologic disease-modifying antirheumatic drugs (except for TAC), but not with biologics, were selected and served as the control group. Changes in disease activity in the two groups during three consecutive IORRA phases were analyzed by adjusting for confounding factors. The median 28-joint disease activity score (DAS28) decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the control group. After adjusting for confounding factors, the decrease in the DAS28 score in the MTX + TAC group was significantly larger (by 0.273 points) than that in the control group (P < 0.05). This study demonstrated the efficacy of add-on therapy with TAC to MTX in patients with RA in daily practice.

Non-synonymous variant (Gly307Ser) in CD226 is associated with susceptibility in Japanese rheumatoid arthritis patients

Abstract: (2013). Non-synonymous variant (Gly307Ser) in CD226 is associated with susceptibility in Japanese rheumatoid arthritis patients. Modern Rheumatology: Vol. 23, No. 1, pp. 200-202.

Evaluation of the efficacy and safety of etanercept 50 mg once weekly in Japanese patients with rheumatoid arthritis and comparison with 25 mg etanercept twice weekly

Abstract: Objective Tumor necrosis factor-a inhibitors have been available in recent years for treating early and established rheumatoid arthritis (RA). Twice-weekly administration of 25 mg etanercept (ETN) has demonstrated efficacy and safety. The objective of this study was to evaluate the efficacy of once-weekly administration of 50 mg ETN (ETN50), and to compare it with that of twice-weekly administration of 25 mg ETN (ETN25). Methods The ETN50 group comprised 29 patients and the ETN25 group 26. The analysis compared changes from baseline in Disease Activity Score in 28 joints (DAS28)‐C reactive protein (CRP) and DAS28‐erythrocyte sedimentation rate (ESR) between the ETN50 and ETN25 groups. Results Overall, 42.3 % of ETN50 patients achieved DAS28‐ESR remission (\2.6), and 76.9 % experienced low disease activity at 24 weeks. Patients in the ETN50 group also experienced more significant improvement in DAS28‐ESR at 4 weeks, higher DAS28‐ESR remission rates, and lower disease activity rates than ETN25 group patients. No serious adverse events were experienced in the safety analysis set (ETN50 group). Conclusion These results suggest that ETN50 can lead to earlier remission and higher remission rates compared with ETN25 in patients with RA.

AB0528 Cost-effectiveness of a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, tocilizumab, in rheumatoid arthritis using IORRA cohort database

Abstract: Background Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, has been developed as a treatment for rheumatoid arthritis (RA). It was first approved in Japan in April 2008, and thereafter in Europe and the US. Although substantial evidence has accumulated regarding the efficacy and safety of tocilizumab for RA, the high cost has been a heavy financial burden for both RA patients and society. No prior research has been conducted concerning the cost-effectiveness of tocilizumab based on clinical data in daily practice. Objectives To examine the cost-effectiveness of tocilizumab for patients with RA using the IORRA cohort database. Methods We conducted a Markov model-based simulation to estimate the cost-effectiveness of tocilizumab (TCZ group) compared with methotrexate alone (MTX group). Patients receiving TCZ or MTX were extracted using the matching method from the IORRA participants, and data from these patients were used to determine most of the model parameters.Health states were defined based on the levels of physical dysfunction according to the J-HAQ (Japanese version of HAQ) score, which were assumed to be associated with costs and utility, and transition probabilities between these states were assumed to differ among the two groups. All parameters in the model including drug change or discontinuation rate, mortality rate, utility score and direct and indirect costs were based on clinical data from the IORRA cohort. Lifetime cumulative costs and quality-adjusted life years (QALYs) were estimated using Monte Carlo simulation in both groups, and the incremental cost-effectiveness ratio (ICER) of tocilizumab was calculated. We used 5.0 million JPY (1 EUR =100 JPY in January 2012) as the allowable threshold of ICER. The time horizon was the lifetime of the cohort, the initial population of 10,000 patients created by random sampling from patient data extracted from IORRA. Utilities and costs were discounted annually at 3.0%. We also conducted a probabilistic sensitivity analysis. Results The lifetime cumulative costs and QALYs were 35.4 million JPY and 11.7 in the TCZ group and 23.3 million JPY and 9.3 in the MTX group, respectively. The average period of low physical dysfunction (J-HAQ Conclusions This study has demonstrated the cost-effectiveness of tocilizumab for the first time, based on data from a large observational cohort representing daily clinical practice in Japan. Disclosure of Interest E. Tanaka: None Declared, E. Inoue: None Declared, D. Hoshi: None Declared, A. Kobayashi: None Declared, N. Sugimoto: None Declared, K. Shidara: None Declared, E. Sato: None Declared, Y. Seto: None Declared, A. Nakajima: None Declared, S. Momohara: None Declared, A. Taniguchi: None Declared, H. Yamanaka Grant/Research support from: IORRA study is supported from 40 pharmaceutical companies; Asahikasei Kuraray Medical Co.,Ltd., Abbott Japan Co.,Ltd., Asahikasei Pharma Corporation, AstellasPharma Inc., AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co.,Ltd., Daiichi Fine Chemical Co.,Ltd., Daiichi Sankyo Co.,Ltd., Dainippon Sumitomo Pharma Co.,Ltd., Eisai Co.,Ltd., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co.,Inc., Janssen Pharmaceutical K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co.,Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co.Ltd., Maruho Co.,Ltd., Mitsubishi Chemical Medience Corporation, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., MSD K.K., Mundipharma K.K., Nippon Chemiphar Co.,Ltd., Nippon Shinyaku Co.,Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co.,Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co.,Ltd., Sanwa Kagaku Kenkyusho Co.,Ltd., Sekisui Medical Co.,Ltd., Shionogi Co.,Ltd., Taishotoyama Pharmaceutical Co.,Ltd., Takeda Pharmaceutical Co. LTD., Teijin Pharma Limited, Torii Pharmaceutical Co.,Ltd., UCB Japan Co. Ltd., ZERIA Pharmaceutical Co.,Ltd., Consultant for: Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe., Pfizer, Takeda, Teijin Pharma, UCB

FRI0124 Assessment of work productivity and activity impairment in patients with rheumatoid arthritis based on the institute of rheumatology rheumatoid arthritis (IORRA) cohort database

Abstract: Background Rheumatoid arthritis (RA) can limit the daily activities of patients and restrict participation in important life activities including work. Indirect costs of RA due to losses such as reduced productivity are an important social issue in addition to rapidly increasing direct costs, but these costs have hardly been studied in Japan. Work status is strongly influenced by cultural differences among the races. Analyses of cost in Japan should be conducted by independently evaluating work disability and productivity in patients with RA in real-world settings. Objectives To evaluate work productivity and activity impairment in patients with RA in Japan using the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. Methods In RA patients who participated in the IORRA in October 2011, a cross-sectional analysis was conducted to determine the influence of RA on work performance as assessed using a well-validated instrument, the Work Productivity and Activity Impairment (WPAI) questionnaire. We also examined associations between work performance and disease activity (DAS28), physical disability (Japanese version of the HAQ; J-HAQ), or quality of life (EQ-5D) score. Results Our analysis included the data of 5700 patients with RA (mean age, 60.3 years; duration of RA, 14.1 years; females, 84.5%; biologics used in 15.4% of the patients). Of these, 2162 patients (37.9%) were paid workers (mean age, 52.6 years: duration of RA, 11.3 years; females, 77.6%; biologics used in 18.3% of the patients). In these paid workers, the mean number of hours of work per week was 35.1, work absence due to RA per week was 1.2, and work absence due to other reasons per week was 5.3. The rates of absenteeism (percent work time missed due to RA), presenteeism (percent impairment while working due to RA, i.e., productivity loss associated with impaired work performance), work productivity loss (percent overall work impairment due to RA [presenteeism plus absenteeism]), and activity impairment (percent activity impairment due to RA) were 2.5%, 16.1%, 17.4%, and 19.8%, respectively (compared with 3.8%, 20.8%, 22.3%, and 27.2%, respectively, among patients treated with biologics). The rate of absenteeism was weakly correlated with DAS28, J-HAQ, and EQ-5D scores (r = 0.18 to 0.26). The rates of presenteeism, work productivity loss, and activity impairment were moderately or strongly correlated with DAS28, J-HAQ, and EQ-5D scores (r = 0.34 to 0.68), with the correlation to J-HAQ (r = 0.51 to 0.63) or EQ-5D (r = 0.56 to 0.68) score being stronger than that to DAS28 (r = 0.34 to 0.39) score. Among RA patients with a J-HAQ score of 1.5 or higher (n=136), the rates of absenteeism, presenteeism, work productivity loss, and activity impairment were 11.7%, 44.1%, 48.2%, and 53.0%, respectively, and were significantly worse compared with the 2.2%, 9.9%, 10.8%, and 11.1%, respectively, observed in RA patients with a J-HAQ score below 0.5 (n=1475). Conclusions In Japanese patients with RA, work productivity and activity impairment are strongly correlated with the extent of physical disability and quality of life. The study results indicate that the key to indirect cost reduction is control of RA before it can cause physical disability and impaired QOL. Disclosure of Interest E. Tanaka: None Declared, E. Inoue: None Declared, D. Hoshi: None Declared, K. Shidara: None Declared, N. Sugimoto: None Declared, Y. Inoue: None Declared, Y. Seto: None Declared, A. Nakajima: None Declared, S. Momohara: None Declared, A. Taniguchi: None Declared, H. Yamanaka Grant/research support from: IORRA study is supported by Asahikasei Kuraray Medical Co., Ltd., Abbott Japan Co., Ltd., Asahikasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Fine Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co., Inc., Janssen Pharmaceutical K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Maruho Co., Ltd., Mitsubishi Chemical Medience Corporation, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., MSD K.K., Mundipharma K.K., Nippon Chemiphar Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sekisui Medical Co., Ltd., Shionogi Co., Ltd., Taishotoyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. LTD., Teijin Pharma Limited, Torii Pharmaceutical Co., Ltd., UCB Japan Co. Ltd., ZERIA Pharmaceutical Co., Ltd., Consultant for: Abbott Japan Co., Ltd, AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Takeda Pharmaceutical Co. LTD., Teijin Pharma Limited, UCB Japan Co. Ltd.

FRI0068 Sustaining remission as defined by the new acr/eular criteria leads to better quality of life in patients with rheumatoid arthritis

Abstract: Background Remission is a therapeutic target in the management of rheumatoid arthritis (RA). New remission criteria proposed by the ACR/EULAR in 2010 must be validated to determine whether they are useful for achieving better long-term outcome. At the 2010 ACR annual meeting, we demonstrated that sustaining remission contributed to maintaining physical function irrespective of which criteria were used and that Boolean-based criteria were better than other criteria. However, the utility of these criteria for maintaining daily quality of life (QOL) in RA patients has not been well elucidated. Objectives To evaluate the improvement of QOL in a large cohort of RA patients (IORRA) who met various remission criteria. Methods The IORRA cohort study is a single-institute, large observational, cohort study of RA conducted in the Institute of Rheumatology, Tokyo Women’s Medical University, Japan. A database of physicians’ assessments, patients’ assessments, and laboratory data has been created and the data have been collected biannually (every April and October) since October 2000. Data collected between April 2008 and October 2010 (six data collections) from 972 RA patients who fulfilled DAS28 remission criteria at least once, were analyzed. These patients were evaluated many times according to different remission criteria (Boolean trial and practice, index of CDAI, SDAI or DAS28). QOL was assessed by the European QOL-5 dimensions (EQ-5D) score. The proportion of patients with EQ-5D score aggravation during the observation period was calculated according to the number of times that patients fulfilled remission criteria. Multivariate analysis of non-aggravation of the QOL score was carried out after adjusting for sex, age, disease duration, body mass index, rheumatoid factor, and physical function measured by the Japanese version of the Health Assessment Questionnaire (J-HAQ). Results Among 972 patients (women, 76.9%; mean age, 57.0 years; disease duration, 11.2 years; baseline DAS28, 2.0; and EQ-5D, 0.875) EQ-5D score was aggravated in 7.6%, 8.6%, 9.1%, 10.2%, and 11.6% of patients who met the Boolean trial, Boolean practice, SDAI index, CDAI index, and DAS28 criteria for all six IORRA data collection periods, respectively. QOL was aggravated in 35.2–38.1% of patients who met DAS28 remission criteria at least once but not other criteria during the 2.5 years of observation. The odds ratio (OR) of aggravated EQ-5D score was 1.66 (95%CI 1.11-2.51, p Conclusions Sustaining remission defined by the new ACR/EULAR criteria (compared to CDAI, SDAI index of remission criteria, or DAS28 remission criteria) results in better QOL in RA patients. To improve long-term QOL in RA patients, fulfillment of the new remission criteria is needed. Disclosure of Interest K. Shidara: None Declared, A. Nakajima: None Declared, E. Inoue: None Declared, D. Hoshi: None Declared, E. Tanaka: None Declared, Y. Inoue: None Declared, A. Kobayashi: None Declared, Y. Seto: None Declared, S. Momohara Speakers bureau: Abbott Japan, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, A. Taniguchi: None Declared, H. Yamanaka Grant/research support from: IORRA study is supported by Asahikasei Kuraray Medical Co., Ltd., Abbott Japan Co., Ltd., Asahikasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Fine Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co., Inc., Janssen Pharmaceutical K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Maruho Co., Ltd., Mitsubishi Chemical Medience Corporation, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., MSD K.K., Mundipharma K.K., Nippon Chemiphar Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sekisui Medical Co., Ltd., Shionogi Co., Ltd., Taishotoyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. LTD., Teijin Pharma Limited, Torii Pharmaceutical Co., Ltd., UCB Japan Co. Ltd., ZERIA Pharmaceutical Co., Ltd., Speakers bureau: Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe., Pfizer, Takeda, Teijin Pharma, UCB

FRI0096 Influence of dose titration of concomitant steroid and methotrexate during biologic therapy on remission rates in patients with rheumatoid arthritis according to the new ACR/EULAR remission criteria in daily practice based on the iorra cohort

Abstract: Background After the introduction of biologics for the treatment of patients with active rheumatoid arthritis (RA), clinical remission has become an achievable and realistic therapeutic goal. In clinical trials, remission rates in patients receiving biologics are assessed under a fixed-dose regimen of steroid and/or methotrexate. However, in daily practice, the dose of concomitant steroid and/or methotrexate is often titrated according to the patient’s response to therapy; thus, remission rates might be influenced by this titration. Objectives To examine the relationship between remission rate and concomitant use of steroid and methotrexate in RA patients after starting biologics therapy in daily practice. Methods We have established a large observational cohort of RA patients, IORRA (Institute Of Rheumatology, Rheumatoid Arthritis), in our institute since October 2000. Essentially all RA patients who attend our clinic are asked to complete questionnaires every 6 months. Clinical information, including physician’s evaluations and laboratory data, is collected biannually (April and October). As a result, more than 5000 RA patients were registered. All RA patients who commenced treatment with biologics from 2008 to 2010 were extracted from the IORRA database. The 28-joint Disease Activity Score (DAS28), remission rate based on the ACR/EULAR remission criteria, and frequencies of use and doses of methotrexate and steroid before treatment and 2 years after initiation of each biologic drug were calculated. Results Average DAS28 before/after the initiation of infliximab (INF: n=98), etanercept (ETA: n=181), tocilizumab (TOC: n=90) and adalimumab (ADA: n=101) were 4.54/2.96, 4.35/2.93, 4.63/2.73 and 4.23/3.30, respectively. The remission rates according to Boolean (trial) criteria/Simplified Disease Activity Index (SDAI)/Boolean (practice) criteria/Clinical Disease Activity Index (CDAI) in patients treated with INF, ETA, TOC and ADA were 14.3%/33.7%/17.4%/29.6%, 26.0%/33.2%/27.1%/31.5%, 15.6%/24.4%/15.6%/22.2% and 20.8%/33.7%/23.8%/30.7%, respectively. The frequencies of use and average dose of steroid in patients treated with biologics (n=470) before treatment and 2 years after initiation of biologics were 58.9% (4.96 mg/day) and 51.5% (4.84 mg/day), respectively. Although both the frequencies of use and doses of steroid decreased during treatment with biologics (with the exception of steroid dose for patients treated with ADA), approximately 50% of patients continued receiving steroids 2 years after starting the biologic agent. The frequencies of use of methotrexate decreased in patients receiving ETA and TOC but increased in patients treated with ADA; doses of methotrexate decreased in patients receiving INF and ETA but increased in patients treated with TOC and ADA. Conclusions Since the concomitant dose of methotrexate and steroid was titrated commonly in RA patients receiving biologics in daily practice, care should be exercised when interpreting remission rates of patients treated with biologics in daily practice. Disclosure of Interest Y. Shimizu: None Declared, E. Tanaka: None Declared, E. Inoue: None Declared, K. Shidara: None Declared, D. Hoshi: None Declared, N. Sugimoto: None Declared, E. Sato: None Declared, Y. Seto: None Declared, S. Momohara: None Declared, A. Nakajima: None Declared, A. Taniguchi: None Declared, H. Yamanaka Grant/Research support from: IORRA study is supported by 40 pharmaceutical companies;Asahikasei Kuraray Medical Co.,Ltd. Abbott Japan Co.,Ltd. Asahikasei Pharma Corporation Astellas harma Inc. AstraZeneca K.K. Bristol-Myers Squibb Chugai Pharmaceutical Co.,Ltd. Daiichi Fine Chemical Co.,Ltd. Daiichi Sankyo Co.,Ltd. Dainippon Sumitomo Pharma Co.,Ltd. Eisai Co.,Ltd. GlaxoSmithKline K.K. Hisamitsu Pharmaceutical Co.,Inc. Janssen Pharmaceutical K.K. Japan Tobacco Inc. Kaken Pharmaceutical Co.,Ltd. Kissei Pharmaceutical Co., Ltd. Kowa Pharmaceutical Co.Ltd. Maruho Co.,Ltd. Mitsubishi Chemical Medience Corporation Mitsubishi Tanabe Pharma Corporation Mochida Pharmaceutical Co., Ltd. MSD K.K., Mundipharma K.K. Nippon Chemiphar Co.,Ltd. Nippon Shinyaku Co.,Ltd. Novartis Pharma K.K. Otsuka Pharmaceutical Co.,Ltd. Pfizer Japan Inc. Sanofi-Aventis K.K. Santen Pharmaceutical Co.,Ltd. Sanwa Kagaku Kenkyusho Co.,Ltd. Sekisui Medical Co.,Ltd. Shionogi Co.,Ltd. Taishotoyama Pharmaceutical Co.,Ltd. Takeda Pharmaceutical Company Limited Teijin Pharma Limited Torii Pharmaceutical Co.,Ltd. UCB Japan Co. Ltd. ZERIA Pharmaceutical Co.,Ltd.Consultancies, speaking fee from Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe., Pfizer, Takeda, Teijin Pharma, UCB.

THU0080 Efficacy of vaccination against pandemic a H1N1 influenza in japanese patients with rheumatoid arthritis - analysis from the iorra cohort -

Abstract: Background A new strain of pandemic influenza emerged in 2009. The Infectious Disease Surveillance Center of Japan reported that almost all influenza occurring from September 2009 to April 2010 in Japan were isolates of the novel pandemic influenza virus A (H1N1) (1). Until now, the efficacy of vaccination against 2009/2010 pandemic influenza in Japanese patients with rheumatoid arthritis (RA) had not been analyzed. Objectives To investigate the efficacy of vaccination against a novel pandemic influenza and determine the risk factors for attack in Japanese patients with RA in a large observational cohort, Institute of Rheumatology, Rheumatoid Arthritis (IORRA). Methods Patients with RA who participated in IORRA survey April 2010 were analyzed. Patients were asked to complete a self-questionnaire survey regarding their vaccination status for pandemic influenza and if they had developed the disease. The efficacy of vaccination and pandemic influenza attack rate were calculated, and factors associated with attacks were analyzed by multiple logistic regression analysis. Age, sex, body mass index (BMI), disease activity, physical dysfunction, use of biologics, doses of methotrexate (MTX) and corticosteroid, and vaccination status were used as explanatory variables in the model. Results A total of 4863 patients (females: 85.6%, mean age: 59.7 years) were analyzed. The percentages of MTX, corticosteroid, and biologics users were 70.5%, 44.8%, and 10.6%, respectively. Approximately one third of patients (1,711, 35.2%) had been vaccinated against influenza, and 148 patients in total developed influenza. Four female RA patients were hospitalized and/or were administered oxygen, and 3 of those patients (75%) had not been vaccinated. The attack rates of vaccinated and unvaccinated patients were 2.2% and 3.5%, respectively. The vaccination odds ratio (OR) for development of influenza was 0.614 (95% confidence interval: 0.414-0.883). Significant risk factors associated with influenza-like illness were no vaccination (OR 1.287, p p Conclusions This study found that vaccination against pandemic influenza was effective for RA patients in the IORRA cohort. No vaccination and older age were significant risks for influenza attacks in the 2009/2010 season, regardless of disease activity or treatment with corticosteroids, MTX, or biologics. References Weekly reports of influenza virus isolation/detection, Japan. http://idsc.nih.go.jp/iasr/prompt/graph/reffig1.gif Disclosure of Interest T. Kobashigawa: None Declared, A. Nakajima: None Declared, E. Tanaka: None Declared, E. Inoue: None Declared, A. Taniguchi: None Declared, S. Momohara: None Declared, H. Yamanaka Grant/Research support from: IORRA study is supported by 40 pharmaceutical companies; Asahikasei Kuraray Medical Co.,Ltd. Abbott Japan Co.,Ltd. Asahikasei Pharma Corporation Astellas harma Inc. AstraZeneca K.K. Bristol-Myers Squibb Chugai Pharmaceutical Co.,Ltd. Daiichi Fine Chemical Co.,Ltd. Daiichi Sankyo Co.,Ltd. Dainippon Sumitomo Pharma Co.,Ltd. Eisai Co.,Ltd. GlaxoSmithKline K.K. Hisamitsu Pharmaceutical Co.,Inc. Janssen Pharmaceutical K.K. Japan Tobacco Inc. Kaken Pharmaceutical Co.,Ltd. Kissei Pharmaceutical Co., Ltd. Kowa Pharmaceutical Co.Ltd. Maruho Co.,Ltd. Mitsubishi Chemical Medience Corporation Mitsubishi Tanabe Pharma Corporation Mochida Pharmaceutical Co., Ltd. MSD K.K., Mundipharma K.K. Nippon Chemiphar Co.,Ltd. Nippon Shinyaku Co.,Ltd. Novartis Pharma K.K. Otsuka Pharmaceutical Co.,Ltd. Pfizer Japan Inc. Sanofi-Aventis K.K. Santen Pharmaceutical Co.,Ltd. Sanwa Kagaku Kenkyusho Co.,Ltd. Sekisui Medical Co.,Ltd. Shionogi Co.,Ltd. Taishotoyama Pharmaceutical Co.,Ltd. Takeda Pharmaceutical Company Limited Teijin Pharma Limited Torii Pharmaceutical Co.,Ltd. UCB Japan Co. Ltd. ZERIA Pharmaceutical Co.,Ltd., Consultant for: Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe., Pfizer, Takeda, Teijin Pharma, UCB, Speakers Bureau: Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe., Pfizer, Takeda, Teijin Pharma, UCB