Showing papers by "Shigeki Momohara published in 2015"
TL;DR: Among patients with high disease activity, treatment with methotrexate and/or biologics and improved DAS28 scores and improved EQ-5D scores were associated with increased CCIA levels, and patients with comorbidities may not experience the same degree of benefit from recent RA treatments compared with patients without comorbridities in daily practice.
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.
41 citations
TL;DR: Despite improvements in rheumatoid arthritis disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in patients with RA.
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. Although rheumatoid arthritis (RA) is a risk factor for osteoporosis and fractures, few studies have described the association between disease activity and the fracture incidence in patients with RA. This study aimed to investigate changes in the non-vertebral fracture incidence between 2001 and 2010 in our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. The IORRA is a prospective observational cohort study of Japanese RA patients. A total of 9,987 patients with RA were enrolled in this cohort from 2000 to 2010. The clinical parameter and non-vertebral fracture occurrence data were collected biannually through self-reported questionnaires. Incidences of self-reported non-vertebral fractures were also analyzed via standardization according to gender, age, and disease activity during each 2-year period. From 2001 to 2010, the percentage of patients with 28-joint disease activity score remission increased from 7.8 to 39.7 %, prednisolone intake decreased from 51.4 to 41.3 %, and bisphosphonate intake increased from 5.0 to 23.4 %. The non-vertebral fracture incidence rates were 24.6/1,000 person-years in 2001 and 35.5/1,000 person-years in 2010, with no apparent change even after standardization. The overall non-vertebral fracture incidence was significantly higher in the autumn/winter than in the spring/summer (p = 0.02). Despite improvements in disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in our patients with RA. Osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the disease control in patients with RA.
38 citations
TL;DR: It is confirmed the associations between vertebral fractures and advanced age, J-HAQ-DI, and high daily prednisolone dose; and found significant correlations between vertebra fractures and female gender, DAS28, and history of any previous fracture in Japanese RA patients.
Abstract: Objective. 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).Methods. 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.Results. 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 In...
29 citations
TL;DR: Destruction of the hand bones in patients with RA was classified into 2 anatomic subgroups, the fingers and the non‐fingers, with the aim of analyzing which factors are associated with destruction of the finger joints.
Abstract: Objective
Rheumatoid arthritis (RA) is a chronic disease leading to joint destruction. Although many studies have addressed factors potentially correlated with the speed of joint destruction, less attention has been paid to the distribution of joint destruction in patients with RA. In this study, destruction of the hand bones in patients with RA was classified into 2 anatomic subgroups, the fingers and the non-fingers, with the aim of analyzing which factors are associated with destruction of the finger joints.
Methods
A total of 1,215 Japanese patients with RA were recruited from 2 different populations. The degree of joint destruction was assessed using the total modified Sharp/van der Heijde score (SHS) of radiographic joint damage. The SHS score of joint damage in the finger joints was used as the dependent variable, and the SHS score in the non-finger joints was used as a covariate. Age, sex, disease duration, smoking, C-reactive protein level, treatment for RA, and positivity for and levels of anti–citrullinated protein antibodies and rheumatoid factor (RF) were evaluated as candidate correlates. Overall effect sizes were assessed in a meta-analysis. In addition, associations observed in the Japanese patients were compared to those in a cohort of 157 Dutch RA patients in the BeSt study (a randomized, controlled trial involving 4 different strictly specified treatment strategies for early RA).
Results
Not surprisingly, disease duration in Japanese patients with RA was associated with the finger SHS score (P ≤ 0.00037). Both positivity for and levels of RF showed significant associations with the finger SHS score after adjustment for covariates (P = 0.0022 and P = 8.1 × 10−7, respectively). These associations were also true in relation to the time-averaged finger SHS score. An association between RF positivity and the finger SHS score was also observed in Dutch patients with RA in the BeSt study (P = 0.049).
Conclusion
Positivity for and levels of RF are associated with finger joint destruction independent of non-finger joint destruction and other covariates. Our findings suggest that there are different mechanisms of joint destruction operating in the finger joints of patients with RA.
26 citations
TL;DR: This study was undertaken to assess the associations of the shared epitope and HLA–DRB1*04:05, the most common share epitope allele in the Japanese population, with joint destruction in patients with ACPA‐positive RA.
Abstract: Objective
The shared epitope is associated with increased joint destruction in rheumatoid arthritis (RA) as well as susceptibility to RA and the production of anti–citrullinated protein antibody (ACPA). However, previous studies addressing whether the association of the shared epitope with joint destruction is independent of ACPA have shown different results in different populations. Different allele distributions in the shared epitope may explain this ethnic heterogeneity. This study was undertaken to assess the associations of the shared epitope and HLA–DRB1*04:05, the most common shared epitope allele in the Japanese population, with joint destruction in patients with ACPA-positive RA.
Methods
A total of 861 patients with ACPA-positive RA who had not received any biologic agents were recruited from the institute of Rheumatology, Rheumatoid Arthritis cohort (sets 1 and 2) and the Kyoto University Rheumatoid Arthritis Management Alliance cohort (set 3). Joint destruction was assessed using the modified Sharp/van der Heijde score (SHS). The associations of the shared epitope alleles, HLA–DRB1*04:05, and other shared epitope allele groups with the SHS were analyzed in a linear regression analysis. Amino acid variations associated with the SHS were also analyzed.
Results
The shared epitope was significantly associated with an increased SHS (P = 0.0017). Although HLA–DRB1*04:05 was significantly associated with an increased SHS (P = 2.7 × 10−5), the group of other shared epitope alleles, including HLA–DRB1*01:01, did not show an association with the SHS in spite of sufficient power (P = 0.67). HLA–DRB1*04:05 was associated with joint destruction in a dose-dependent manner. Analyses of amino acid associations of HLA–DRB1 revealed that serine at position 57, recently shown to have a susceptibility effect for ACPA-positive RA in Asian populations, showed a significant association (P = 5.0 × 10−6).
Conclusion
HLA–DRB1*04:05, characterized by serine at position 57, accounts for the detrimental association between the shared epitope and SHS in Japanese patients with ACPA-positive RA.
25 citations
TL;DR: Many of the susceptibility loci were shared between ACPA-positive and -negative RA, and positive correlations were not observed between the ACpa-negative two subpopulations.
Abstract: Although susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA. We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Rs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p = 5.7 × 10−8), followed by rs6986423 in CSMD1 (p = 2.4 × 10−6) and rs17727339 in FCRL3 (p = 1.4 × 10−5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Many of the susceptibility loci were shared between ACPA-positive and -negative RA.
23 citations
TL;DR: This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.
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 zosterResults A total of 7,986 patients (female 831%) accumulated 30,140 patient-years of observation, and 366 events were confirmed The standardized incidence rate per 1,000 patient-years was 91 (95% confidence interval (CI) 62–129) in total, 78 (36–148) in men, and 103 (68–150) in women The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1268, 95% CI 1153–1393, p < 00001), high disease activity compared with remission (HR 1642, 95% CI 1067–2528, p < 005), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1531, 95% CI 1211–1936, p < 0001; ≥ 5 mg/day compared with 0 mg
21 citations
TL;DR: This study undertook this study to elucidate the associations between particular amino acid positions in HLA–DRB1 and ACPA levels in patients with RA.
Abstract: Objective
Anti–citrullinated protein antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA), and strong associations between HLA–DRB1 alleles and ACPA levels have been detected in RA patients. We undertook this study to elucidate the associations between particular amino acid positions in HLA–DRB1 and ACPA levels in patients with RA.
Methods
We analyzed ACPA data on a total of 4,371 Japanese ACPA-positive RA patients in whom HLA–DRB1 allele genotyping had been performed. Generalized linear regression analysis and omnibus testing were carried out to determine associations of HLA–DRB1 alleles, amino acid residues, or amino acid positions with levels of ACPA.
Results
HLA–DRB1*09:01 and HLA–DR15 were confirmed to be associated with ACPA levels. HLA–DRB1*08:03 and DRB1*14:06 were associated with reduced and increased ACPA levels, respectively. We detected a strong association between ACPA levels and amino acid position 74 (P = 1.9 × 10−51). The association was mainly conferred by alanine residue (P = 4.5 × 10−51). After adjustment for position 74, amino acid positions 60 and 57 were found to be associated with ACPA levels. Amino acid positions 74 and 57 had previously been reported to be associated with susceptibility to ACPA-positive RA in Asians. Combinations of the amino acid residues at position 74 and position 60 or 57 could induce improvement in Akaike's information criterion comparable to that induced by the 5 significant HLA–DRB1 alleles (HLA–DRB1*08:03, DRB1*09:01, DRB1*14:06, DRB1*15:01, and DRB1*15:02).
Conclusion
Amino acid position 74 in HLA–DRB1 is strongly associated with ACPA levels in ACPA-positive RA, as well as with RA susceptibility. The mechanisms of ACPA production and susceptibility to ACPA-positive RA seem to partly overlap.
19 citations
TL;DR: QuickDASH seems suitable for evaluating upper extremity impairment, disability index, and disease control in a large cohort of RA patients including elderly patients and change in QuickDASH score and DAS28-based European League Against Rheumatism response showed significant correlation.
Abstract: Objective. First objective is to validate the Disabilities of the Arm, Shoulder and Hand (DASH) and Quick DASH (QuickDASH) questionnaire in rheumatoid arthritis (RA) patients with functional upper extremity impairment. Next is to clarify which clinical factor is associating with QuickDASH using a large cohort of RA.Methods. The QuickDASH and DASH were applied to our 94 RA patients who underwent surgery for functional upper extremity impairment. Next, the QuickDASH was applied to our cohort of 5191 Japanese patients with RA.Results. In the first cohort of 94 RA patients, both QuickDASH and DASH displayed excellent reliability and validity. The response rate of patients < 65 and ≥ 65 years of age showed significant difference in the DASH but not in the QuickDASH. In the second cohort with 5191 RA patients, QuickDASH showed a high response rate (93%) and good to moderate correlation with Japanese version of the Health Assessment Questionnaire (r = 0.88) and disease activity score of 28 (DAS28, r = 0....
16 citations
TL;DR: 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.
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-tim...
16 citations
TL;DR: It is demonstrated that the effect of smoking on remission proportions differed between men and women, and both sex and smoking status are important considerations when planning a treatment strategy for patients with RA.
Abstract: Objective. To analyze sex difference in the effect of smoking on remission proportions in patients with rheumatoid arthritis (RA). Methods. 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. Results. 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]. Conclusion. 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.
TL;DR: SAFE-Q is a useful tool for assessing the foot and ankle in RA patients and has moderate correlations with the JSSF-RA and JHAQ, and a low correlation was observed between the SAFE-Q and DAS28, SDAI, and CDAI.
Abstract: Objectives. A self-administered foot evaluation questionnaire (SAFE-Q) was developed by the Japanese Society for Surgery of the Foot (JSSF). The aim of this study is to evaluate the validity and responsiveness of the SAFE-Q in patients with rheumatoid arthritis (RA).Methods. In total, 180 patients with RA answered the SAFE-Q. Of 180 patients, 34 answered the SAFE-Q twice, preoperatively and postoperatively, to assess responsiveness. Construct validity was tested by comparing the 5 SAFE-Q subscales and the JSSF standard rating system for the RA foot and ankle scale (JSSF-RA), a Japanese version of the Health Assessment Questionnaire (JHAQ), disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). Responsiveness was examined by calculating the standardized response mean (SRM) and effect size (ES) 3 months after surgery.Results. There were moderate correlations between the SAFE-Q and the JSSF-RA and JHAQ. Conversely, a low corr...
TL;DR: 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.
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 init...
TL;DR: Patients with more recent disease onset showed an improved outcome and establishing and sharing a transition program among pediatric and non-pediatric rheumatologists is desirable.
Abstract: Objective. To evaluate the long-term outcome of patients with juvenile idiopathic arthritis (JIA) using data from a large cohort database, Institute of Rheumatology, Rheumatoid Arthritis, managed by the Tokyo Women's Medical University.Methods. Of 182 patients identified from the database from 2000 to 2013, 114 were verified as having JIA. The transition of medical care and the contributions of biological DMARDs were evaluated.Results. The mean age of the patients (93 females, 81.6%) at the latest examination was 36.6 ± 13.3 years. The mean age at disease onset and mean disease duration were 11.6 ± 3.4 and 25.0 ± 13.3 years, respectively. Of the 114 patients, 106 (93.0%) had poly- or oligoarthritis. Only one-fourth transferred from general pediatricians or pediatric rheumatologists. More patients with recent disease onset were treated with biological DMARDs (16.7% in the 1970s, vs. 80.0% in the 2000s). Disease activity assessed with DAS28 was significantly lower when disease onset was more recent ...
TL;DR: Both GLM 50-mg and 100-mg regimens are effective in patients with rheumatoid arthritis in daily practice.
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 significan...
TL;DR: It is suggested that preventing quality of life deterioration without steroid use might be important in stopping the progression of work impairment, and that the use of biologics did not have a significant impact.
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.
TL;DR: Evidence is provided that the C677T polymorphism contributes to an increased risk of hip fracture in Japanese patients with rheumatoid arthritis and that the association with incident fracture risk has been conflicting among studies.
Abstract: Background Patients with RA have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Although several clinical factors influence osteoporotic fracture 1 , multiple genetic loci are also involved in the pathogenesis 2 . Elevated levels of circulating homocysteine have been reported to inhibit the formation of collagen cross-links, resulting in fragile bones and the occurrence of osteoporotic fracture 3 . The activity of the methylene tetrahydrofolate reductase (MTHFR) enzyme affects levels of circulating homocysteine, but association of the MTHFR gene with osteoporotic fracture has been conflicting among studies. Previously, we reported no association of the MTHFR C677T polymorphism with incident fracture risk 4 . In the present study, we extended the dataset to enhance the statistical power and reviewed the association between the C677T polymorphism and the occurrence of hip fracture in Japanese patients with RA. Objectives The purpose of this study was to investigate the association of the MTHFR C677T polymorphism with the occurrence of hip fracture in Japanese patients with RA. Methods This study included 2282 Japanese patients with RA, who participated in the Institute of Rheumatology Rheumatoid Arthritis cohort study (IORRA). The MTHFR C677T polymorphism was genotyped in the DNA samples. The occurrence of hip fracture after enrollment in IORRA was determined from the response to a patient questionnaire every 6 months from October 2000 to October 2010. The data were confirmed by review of medical records. A total of 40 hip fractures in 40 patients were identified and included in this study. A multivariate Cox proportional hazards model was performed in order to examine the association between the number of risk alleles of the C677T polymorphism with the occurrence of hip fracture. Results A multivariate Cox proportional hazards model showed that patients with more risk alleles of the C677T polymorphism had a higher risk of hip fracture (HR [95% CI] =1.63 [1.06 to 2.50], P =0.025). Conclusions Our results demonstrated that the MTHFR C677T polymorphism was significantly associated with the occurrence of hip fracture. Extending the dataset to 2282 patients with RA resulted in a different finding from the previous study. The present data support evidence that the C677T polymorphism contributes to an increased risk of hip fracture. References Furuya T, et al. Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis: a prospective observational cohort study. Osteoporos Int. 2013 Apr;24(4):1257-1265. Styrkarsdottir U, et al. Multiple genetic loci for bone mineral density and fractures. N Eng J Med. 2008 May 29;358(22):2355-2365. van Meurs JB, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004 May 13;350(20):2033-2041. Urano W, et al. Associations between methotrexate treatment and methylenetetrahydrofolate reductase gene polymorphisms with incident fractures in Japanese female rheumatoid arthritis patients. J Bone Miner Metab. 2009;27(5):574-583. Acknowledgements We thank all DNA donors for making this study possible. We appreciate all the members of Institute of Rheumatology, Tokyo Women9s Medical University for their effort on the IORRA cohort. We are also grateful to Ms Kaori Arai, Ms Nao Satomi and Ms Yuka Sato for their technical assistance. Disclosure of Interest S. Yoshida: None declared, K. Ikari: None declared, T. Furuya: None declared, A. Taniguchi: None declared, H. Yamanaka Grant/research support from: Abbott, AbbVie, Asahikasei, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taishotoyama, Takeda, Teijin Consultant for: Abbott, AbbVie, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Takeda, Teijin, Consultant for: Abbott, AbbVie, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Takeda, Teijin., Speakers bureau: Abbott, AbbVie, Astellas, Bristol-Myers Squib, Chugai, Eisai, Mitsubishi Tanabe, Pfizer, Takeda, Teijin.S., S. Momohara Speakers bureau: Abbvie Japan, Chugai Parmaceutical, Eisai, Mitsubishi Tanabe Parma, Takeda Parmaceutical