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Objectives: This study aimed to examine the relationship between daily physical activity and the phase angle (PhA) obtained by bioelectrical impedance analysis in rheumatoid arthritis (RA) patients., Methods: Data from a prospective cohort study of RA patients who were surveyed every year were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and physical activity was assessed as the amount of time of exercise in metabolic equivalents (METs) per day using a triaxial accelerometer for 7 consecutive days. The association between physical activity and the PhA was evaluated using the isotemporal substitution model in multiple regression analysis., Results: Seventy-six RA patients were included in the analysis (81% female and age 66.2 ± 13.1 years). On cross-sectional analysis, the isotemporal substitution model in multiple regression analysis showed that the PhA was 0.05 points higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .01). Over 1 year, the rate of change in the PhA was 0.69% higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .037)., Conclusion: The PhA in RA patients may be related to physical activity level., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6-8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5-15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objectives: Clinical results of mobile-bearing total ankle arthroplasty (TAA) for rheumatoid arthritis (RA) have been reported, but no studies have compared osteoarthritis (OA) and RA. Clinical and radiographic outcomes after at least 3 years were compared between OA and RA., Methods: Eleven ankles with OA and 22 ankles with RA were followed after mobile-bearing TAA (FINE total ankle system). Clinical outcomes were assessed by the American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiographic outcomes were evaluated by the angular position of the implant, radiolucent lines, migration, and subsidence. Operative and postoperative complications were assessed., Results: There were no significant differences in clinical outcomes, radiographic outcomes, or complications, except the final follow-up AOFAS total score (OA: 89.4 vs RA: 78.2; p = .044) and pain score (OA: 37.3 vs RA: 30.5; p = .041) at a mean follow-up of 83.4 months. Delayed wound healing occurred in 9.1% in RA and none in OA. Radiolucent lines were observed in 45% of both groups, and implant removal was performed in 9.1% and 18.2% of OA and RA, respectively; there were no significant differences., Conclusions: The final follow-up AOFAS total score and pain score were significantly higher in OA after the FINE total ankle system. There was a discrepancy between radiographic abnormalities and implant removal in both OA and RA., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study investigated whether the phase angle (PhA) on bioelectrical impedance analysis is related to frailty in rheumatoid arthritis (RA) patients., Methods: Data from a prospective cohort study of RA patients were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and frailty was assessed by the Kihon Check List (KCL) annually. The cut-off value of the PhA for frailty was calculated by receiver-operating characteristic analysis. The relationships between the PhA and frailty were evaluated by logistic regression analysis. The relationships between the change in PhA and frailty status and the KCL score were evaluated by analysis of covariance and multiple regression analysis., Results: A total of 170 patients (81.2% female, 66.2 ± 13.1 years) were included in the analysis. A PhA of less than the cut-off for frailty was significantly associated with frailty (odds ratio: 4.75, 95% confidence interval: 1.86, 12.17). The change in the PhA was significantly associated with the change in the KCL score (β = -0.15). In robust patients, there was a significant difference in the rate of change of the PhA between the group that became pre-frail in the next year and the group that remained robust., Conclusions: The PhA may be associated with frailty in RA patients., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of this study was to evaluate the new incidence of carotid plaques in rheumatoid arthritis (RA) patients over a 6-year prospective follow-up and to assess the risk factors., Methods: This is a 10-year prospective cohort study that included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017., Results: There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = .936). The mean Disease Activity Score 28-C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% confidence interval, 0.348-1.440; p = .340). An average glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% confidence interval, 1.641-44.455; p = .011)., Conclusions: Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: In 2018, the Global Leadership Initiative on Malnutrition (GLIM) released a global standard for evaluating malnutrition. The etiologies of malnutrition in the GLIM criteria includes disease burden/inflammation, but how this view affects nutritional assessment remains unclear. This study aimed to investigate the impact of disease burden/inflammation on the proportion of malnourished patients defined by GLIM criteria, and how differences in methods for determining disease burden/inflammation in GLIM criteria affect existing nutritional indices among patients with rheumatoid arthritis (RA). We also investigated factors associated with malnutrition in RA patients., Methods: Data from 135 female RA patients (66.8 ± 12.6 years) were cross-sectionally analyzed. Among the etiologies of malnutrition, disease burden/inflammation was defined as: (1) moderate or higher disease activity score (disease activity score composite of the 28-joint score and erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2) [DAS-malnutrition (MN)]; (2) elevated C-reactive protein (CRP) ≥0.5 mg/dL (CRP-MN); and (3) presence of RA (RA-MN). In each of the three conditions, nutritional indicators between well-nourished and malnourished groups were compared by analysis of covariance. Factors associated with malnutrition were analyzed with logistic regression analysis., Results: The frequencies of malnutrition as defined by DAS-MN, CRP-MN, and RA-MN were 39%, 30%, and 71%, respectively. When malnutrition was defined by the DAS-MN and/or the CRP-MN, grip strength and serum ceruloplasmin, iron, and zinc levels showed significant differences between the well-nourished and malnourished groups (p < 0.05). The use of targeted synthetic or biological disease-modifying antirheumatic drugs (ts-/b-DMARD) (OR = 0.29; 95% CI 0.11-0.82), grip strength (OR = 0.83; 95% CI 0.75-0.91), subjective reduction in walking speed (OR = 5.24; 1.85-14.86) were significantly associated with malnutrition as determined by DAS-MN., Conclusion: Differences in disease burden/inflammation affect nutritional assessments. The number of malnourished patients with RA was negatively associated with the use of ts-/b-DMARDs and high physical function in women., Competing Interests: Declaration of competing interest Yoshinari Matsumoto, Yuko Sugioka, Masahiro Tada, Kenji Mamoto, and Daiki Habu declare that they have no competing interests. Tadashi Okano. Grant/research support from: Asahi Kasei, Astellas, Abbvie, Amgen, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead Sciences, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Pfizer, Sanofi, Takeda, UCB, Speakers bureau from: Asahi Kasei, Astellas, Abbvie, Amgen, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead Sciences, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Pfizer, Sanofi, Takeda, UCB. Kentaro Inui. Grant/research support from: Abbvie GK, Mitsubishi Tanabe Pharma, Eisai Co., Ltd., Daiichi Sankyo Co. Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, Novartis, Nippon Kayaku, Speakers bureau from: Janssen Pharmaceutical K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, Novartis, Asahi Kasei Pharma. Tatsuya Koike. Grant/research support from: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB, Speakers bureau from: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objectives: The phase angle (PhA) is an index derived by bioelectrical impedance analysis that reflects the fragility of cell membranes, muscle mass, muscle strength, and nutritional status, and a decrease in PhA might be associated with falls. This study aimed to investigate the relationships of the PhA with sarcopenia and falls in patients with rheumatoid arthritis (RA)., Methods: Data from a prospective cohort study of 189 patients with RA (age 66.5 ± 13.3 y; 80% women) were analyzed. PhA, muscle mass, and grip strength (GS) were evaluated. Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2014 criteria. The correlation between PhA and GS was investigated, and the cutoff value of the PhA for falls during a 2-y period was estimated with a receiver operating characteristic curve analysis. The effects of the PhA and sarcopenia on falls were examined with a Cox proportional hazards model., Results: Of the 189 patients, 48 (25.4%) had falls. The PhA was significantly positively correlated with GS (r = 0.58; P < 0.001). The cutoff values for the PhA for falls were 4.06° for women and 5.26° for men. In the Cox proportional hazards model adjusted for sex, age, disease activity, glucocorticoid use, and activities of daily living at baseline, the hazard ratio for falls was significantly higher when the PhA was below the cutoff value at baseline (hazard ratio: 2.29; 95% confidence interval, 1.18-4.45). Sarcopenia was not a significant risk factor for falls., Conclusions: The PhA might be a useful surrogate marker to predict falls in patients with RA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Activities of daily living in patients with rheumatoid arthritis (RA) have been evaluated by patient-reported outcomes. However, it has been difficult to measure activity intensity quantitively. Calories expended, exercise, and steps were measured quantitively by a wearable activity meter, and their associations with patients' background characteristics were examined., Methods: Data from a prospective, observational study (CHIKARA study) were used. Eighty-five of 100 RA patients were entered and wore a wearable activity meter for 7 days. The daily calories expended and exercise for both walking and housework and steps were evaluated. Total daily calories expended and exercise was defined as the sum of walking and housework. The relationships of DAS28-ESR, mHAQ, body composition, muscle function, and general status were analyzed., Results: The median age was 66.0 years, and the disease duration was 5.3 years. DAS28-ESR was 3.11, and mHAQ was 0.125. Total daily calories expended, exercise, and number of steps were 461.7 kcal, 3.97 METs h, and 4,788, respectively. MHAQ, walking speed, power, locomotive syndrome, and frailty were independently related to exercise. Total daily exercise and steps of the moderate and high disease activity group were significantly lower than those of the remission group. When the number of steps was < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively, using Fisher's exact test (P < 0.001)., Conclusions: Daily physical activity and number of steps were significantly decreased in RA patients with moderate and high disease activity as measured by a wearable activity meter. Key Points • Total daily calories expended and exercise for both walking and housework and steps in patients with rheumatoid arthritis were 461.7 kcal, 3.97 METs h, and 4,788, respectively, using a wearable activity meter. • Daily physical activity, especially total daily exercise and number of steps, was significantly decreased in RA patients with moderate and high disease activity. • When total daily steps were < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background & Aims: To examine the relationship between changes in skeletal muscle mass and lipid metabolism and glycometabolism in patients with rheumatoid arthritis (RA)., Methods: Data were analyzed from 148 female RA patients and 145 age-matched non-RA (control) female subjects from a prospective cohort study (TOMORROW; TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality study). Appendicular skeletal muscle mass (ASM) was assessed using dual-energy x-ray absorptiometry and skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. The reference value for SMI in Asian women, 5.4 kg/m 2 , was used to define low SMI. Data were assessed using cross-sectional (2010 baseline data) and longitudinal (change in value from 2010 to 2013) methods from the retrospective cohort., Results: At baseline in RA patients, the low SMI group showed significantly higher low-density lipoprotein cholesterol (LDL-chol) (p = 0.015), apolipoprotein (Apo)B (p = 0.046), and ApoB-to-A1 (ApoB/A1) (p = 0.025) than the normal SMI group. In multiple regression analysis of RA patients, sequential changes from 2010 to 2013 (Δ) in SMI and ApoB and ApoC2 showed significant negative relationships (β = -0.19, -0.18, respectively) even after adjusting for age, RA duration, exercise habits, medication for RA, disease severity, activities of daily living (ADL) and body fat mass. No significant relation was evident between ΔSMI and various glycometabolism parameters in RA patients., Conclusions: Skeletal muscle mass might be related to lipid metabolism in RA patients. This relationship is independent of factors such as disease severity and body fat mass., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The dietary inflammatory index (DII®), a quantitative measure of the inflammatory potential of daily food and nutrient intake, and associations between a variety of health outcomes have been reported. However, the association between DII score and disease activity of rheumatoid arthritis (RA) is unclear. Therefore, this study was designed to test whether higher DII score contributes to disease activity and as a corollary, whether reducing DII score helps to achieve or maintain low disease activity or remission in patients with RA., Methods: We performed a cross-sectional and longitudinal analysis using 6 years of data (from 2011 to 2017) in TOMORROW, a cohort study consisting of 208 RA patients and 205 gender- and age-matched controls started in 2010. Disease activity of RA patients was assessed annually using DAS28-ESR (disease activity score 28 joints and the erythrocyte sedimentation rate) as a composite measure based on arthritic symptoms in 28 joints plus global health assessment and ESR. Dietary data were collected in 2011 and 2017 using the brief-type self-administered diet history questionnaire (BDHQ). Energy-adjusted DII (E-DII™) score was calculated using 26 nutrients derived from the BDHQ. Data were analyzed with two-group comparisons, correlation analysis, and multivariable logistic regression analysis., Results: One hundred and seventy-seven RA patients and 183 controls, for whom clinical and dietary survey data were available, were analyzed. RA patients had significantly higher E-DII (pro-inflammatory) score compared to controls both in 2011 and 2017 (p < 0.05). In RA patients, E-DII score was not a factor associated with significant change in disease activity. However, anti-inflammatory change in E-DII score was associated maintaining low disease activity (DAS28-ESR ≤ 3.2) or less for 6 years (OR 3.46, 95% CI 0.33-8.98, p = 0.011)., Conclusions: The diets of RA patients had a higher inflammatory potential than controls. Although E-DII score was not a factor associated with significant disease activity change, anti-inflammatory change in E-DII score appeared to be associated with maintaining low disease activity in patients with RA., Trial Registration: UMIN Clinical Trials Registry, UMIN000003876 . Registered 7 Aug 2010-retrospectively registered.

Aim: Patients with rheumatoid arthritis (RA) have a higher risk of falls and fractures due to muscle weakness and painful joints of the lower extremities. Evaluation of muscle functions is important to predict falls and fractures. The aim was to investigate the relationships of muscle functions with falls and fractures in RA patients., Methods: Stand-up muscle power, speed, and stabilizing time were evaluated by a muscle function analyzer in 90 RA patients in the CHIKARA study (UMIN000023744). The relationships of the muscle functions with falls, fractures, body composition, Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified Health Assessment Questionnaire (mHAQ) scores, Steinbrocker class, stage, sarcopenia, and frailty were investigated in a cross-sectional study., Results: Each parameter of muscle function was related to age, falls, frailty, and the leg muscle score. However, only stabilizing time was related with fractures (r = .217, P = .04). When stabilizing time was ≥ 1.13 and ≥1.36 seconds, the odds ratios for falls and fractures were increased 6.2-fold compared to < 1.13 seconds (95% CI: 1.2-20.1, P = .002) and 11.4-fold compared to <1.36 seconds (95% CI: 1.7-92.5, P = .071), respectively. Sarcopenia and skeletal muscle mass were not significantly related to each muscle function. There was a negative correlation between DAS28-ESR and power. Steinbrocker class and mHAQ had negative correlations with power and speed., Conclusions: Sarcopenia and skeletal muscle mass were not adequate indicators of muscle functions in RA patients. Analyzing muscle functions is helpful to predict falls and fractures. Patients with extended stabilizing times should recognize the increased risk of falls and fractures., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background Context: Rheumatoid arthritis (RA) can affect the spine; however, the epidemiology of lumbar lesions and/or low back pain (LBP) in RA patients has not been well-studied., Purpose: The purpose of this study was to compare the prevalence of lumbar lesions and LBP in RA patients with that in healthy volunteers, and to elucidate the influence of RA on lumbar disease., Study Design: Cross-sectional analysis in a cohort study with age- and sex-matched healthy volunteers., Patient Sample: This study included 185 patients with RA and 188 gender/age-matched healthy volunteers without RA., Outcome Measures: Lumbar spondylolisthesis and prevalent vertebral fractures were evaluated using plain lateral X-ray images. Thoraco-lumbar scoliosis was evaluated using dual-energy X-ray absorptiometric images. LBP was assessed using the visual analogue scale (VAS) and Rolland-Morris disability questionnaire (RDQ)., Methods: The prevalence of radiological lumbar lesion and LBP was compared between the RA and control groups. In the RA group, factors associated with lumbar lesion and LBP were analyzed using a multiple logistic regression model., Results: The prevalence rates of spondylolisthesis and prevalent vertebral fracture were significantly higher in the RA group than in the control group; the prevalence of thoraco-lumbar scoliosis tended to be higher in the RA group. There was no significant difference in the average LBP-VAS between the groups. However, the percentage of analgesic drug use was significantly higher, and RDQ scores tended to be worse in the RA group than the control group. Multivariate analysis revealed that age and disease activity score were both related to LBP in the RA group., Conclusions: RA patients are more likely to have radiological lumbar lesions. LBP in RA patients is well controlled, similar to the level in the healthy population; however, disease activity was related to LBP in RA patients. These results suggest that disease control is important for lumbar care in RA patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Patients with rheumatoid arthritis (RA) are at higher risk of sarcopenia because of joint dysfunction and chronic inflammation. The present study aimed to investigate the predictors or risk factors for developing sarcopenia in RA patients using the prospective observational CHIKARA database. We hypothesized that older age, higher disease activity, lower physical function, and glucocorticoid (GC) use are risk factors for sarcopenia., Methods: A total of 100 consecutive RA patients participated in the CHIKARA study. Their body compositions were examined using a body composition analyzer. Laboratory data, disease activity, physical function, and treatment were investigated. Sarcopenia was assessed at baseline and at 1 year. Predictors or risk factors for sarcopenia development at 1 year were investigated by univariate and multivariate analyses., Results: Of 68 patients without sarcopenia at baseline, 9 (13.4%) developed sarcopenia over the year. Univariate analysis showed that age (r = 0.28, p = 0.022), average GC dose over the year (r = 0.25, p = 0.043), and body mass index (r = - 0.28, p = 0.019) were significantly associated with the development of sarcopenia. Average GC use at ≥ 3.25 mg/day was a significant factor on multivariate analysis (odds ratio 8.81, 95% confidence interval 1.14-67.9, p = 0.037)., Conclusions: RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia. Reduction or withdrawal of GCs may prevent sarcopenia.Key Points• Patients with RA are at higher risk of sarcopenia.• Predictors or risk factors for developing sarcopenia over 1 year in RA patients were investigated using the prospective observational CHIKARA database.• RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia.• Reduction or withdrawal of GCs may be essential to prevent sarcopenia.

Aim: Frailty is defined as the degradation of physical and cognitive function in older adults. The relationship between frailty and disease activity in patients with rheumatoid arthritis is unclear. Factors related to frailty in Japanese rheumatoid arthritis patients were investigated in a cross-sectional analysis., Methods: Of 100 patients who entered the prospective, observational Correlation research of sarcopenia, skeletal muscle and disease activity in rheumatoid arthritis (CHIKARA) study, 95 completed a frailty check list (maximal score 25), and were classified as frail (8-25 points), pre-frail (4-7 points) and normal (0-3 points). The relationship with disease activity was investigated in the frailty, pre-frailty and normal groups. Relationships between clinical variables and frailty were evaluated by univariate and multiple logistic regression analyses., Results: The prevalences of frailty, pre-frailty and normal were 18.9%, 38.9% and 42.2%, respectively. The disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3 and modified health assessment questionnaire were higher in the frailty group. In remission, 66.6% were normal and 6.7% had frailty, but with moderate and high disease activity, 13.3% were normal and 46.7% had frailty. On univariate analysis, factors positively related to frailty were age, locomotive syndrome, disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3, use of biological disease-modifying antirheumatic drugs or targeted synthetic disease-modifying antirheumatic drugs, Steinbrocker class and modified health assessment questionnaire; and the leg muscle score and grip strength were negatively related. Matrix metalloproteinase 3 was the only independent factor on multivariate logistic analysis. In patients aged >60 years, this tendency was similar., Conclusions: Frailty was found to be related to disease activity and physical function in rheumatoid arthritis. Control of disease activity appears important to prevent frailty. Geriatr Gerontol Int 2019; 19: 1220-1225., (© 2019 Japan Geriatrics Society.)

Aim: Patients with rheumatoid arthritis (RA) show lower muscle mass and a higher prevalence of sarcopenia than healthy individuals. Correlations between sarcopenia and disease activity, physical function, laboratory data and body composition at baseline were investigated in a prospective, observational study (CHIKARA study) of RA patients., Methods: Body composition was measured using a bioelectrical impedance analyzer. Parameters were compared between sarcopenia and non-sarcopenia groups, and correlations between sarcopenia and Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified health assessment questionnaire, treatment, and laboratory data, including matrix metalloproteinase 3 (MMP3), were investigated., Results: The participants were 100 patients with RA (women, 78%; mean age, 66.1 years). Mean disease duration was 5.5 years, DAS28-ESR was 3.55 and the prevalence of sarcopenia was 28%. Median C-reactive protein (CRP) and MMP3 were significantly higher in the sarcopenia group (0.21 mg/dL and 103.4 ng/mL) than in the non-sarcopenia group (0.11 mg/dL and 70.3 ng/mL). Sarcopenia was negatively correlated with weight, body mass index (BMI), muscle mass, body fat mass, estimated bone mass and basal metabolic rate, and positively correlated with Steinbrocker stage, CRP and MMP3 on univariate analyses. BMI, body fat mass and MMP3 were independently associated with sarcopenia on multivariate logistic regression analysis. When MMP3 was ≥ 90.7 ng/mL, the odds ratio for sarcopenia was increased 3.1-fold compared with < 90.7 ng/mL (P = 0.018)., Conclusion: The prevalence of sarcopenia was 28% in patients with RA whose disease activity was mild. Low BMI, high fat mass and high MMP3 were independently associated with sarcopenia. MMP3 might be a useful marker for sarcopenia in patients with RA., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.

To evaluate work disability and associated factors in patients with rheumatoid arthritis (RA) who participated in the TOMORROW study, a 10-year cohort study in Japan. Subjects in this cross-sectional analysis comprised 191 RA patients and 191 age- and sex-matched non-RA individuals. Work-related outcomes were measured using the Work Productivity and Activity Impairment questionnaire by employment status (full-time worker (FTW), employed ≥ 35 h/week; part-time worker (PTW), < 35 h/week; home worker (HW), non-employed). In addition, we assessed the EuroQol-5 Dimensions (EQ-5D) and Health Assessment Questionnaire (HAQ) to evaluate quality of life and activities of daily living. No significant differences were evident between groups in percentages of participants in each employment status (p = 0.11), percentages of absenteeism (FTW, p = 1.00; PTW, p = 0.29), presenteeism (FTW, p = 0.23; PTW, p = 0.54), overall work impairment (FTW, p = 0.23; PTW, p = 0.73), or percentage of activity impairment (AI) (FTW, p = 0.62; PTW, p = 0.60). In the HW group, percentage of AI was higher in RA patients than that in non-RA patients (p < 0.01). Among RA patients, HW showed lower EQ-5D and higher HAQ than FTW or PTW (p < 0.001 each). Higher disease activity was observed in HW than FTW (p < 0.01). In terms of the effect of biological disease-modifying anti-rheumatic drugs, no significant differences in work-related outcomes, health status, or daily activity were evident between users and non-users. No significant differences in employment status or work impairment were seen between RA and non-RA groups among paid workers. HW with RA showed more impaired daily activity and higher disease activity compared to working RA patients., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000003876 . Registered 1 Jun 2010.

We investigated the influence of abatacept (ABT) on bone mineral density (BMD) and bone metabolic markers (BMMs) in patients with rheumatoid arthritis (RA) compared to other biologic disease-modifying anti-rheumatic drugs (bDMARDs). This prospective, comparative, non-randomized study (the AIRTIGHT study; UMIN000005570) investigated the effects of ABT and other bDMARDs on bone metabolism. A total of 165 RA patients were divided into ABT (n = 50) and non-ABT (n = 115). We evaluated percentage changes in BMD (%ΔBMD) at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Urinary levels of cross-linked N-telopeptide of type I collagen (uNTx) and bone-specific alkaline phosphatase (BAP) were used as markers of bone resorption and formation, respectively. No significant differences in 1-year completion rates were seen between ABT (64%) and non-ABT (72%; p = 0.387). The %ΔBMD at the femoral neck was significantly higher in the ABT group (0.97%) than in the non-ABT group (- 2.19%; p = 0.026). Whereas, no significant difference in %ΔBMD at the lumbar spine was observed between groups (ABT, - 0.40%; Non-ABT, - 1.67%; p = 0.524). No significant differences were observed in changes to uNTx or BAP. ABT treatment was significantly associated with increased BMD at the femoral neck (odds ratio (OR) 8.84; 95% CI 1.08-72.4; p = 0.04), and baseline lumbar osteoarthritis was significantly associated with BMD at the lumbar spine (OR 2.97; 95% CI 1.23-7.13; p = 0.02). The efficacy of ABT for increasing BMD at the femoral neck was superior to that of other bDMARDs. ABT may offer good efficacy for improving BMD at the femoral neck in patients with RA.

Background & Aims: The Mediterranean diet is reportedly effective in suppressing disease activity in rheumatoid arthritis (RA), but the key elements responsible for this effect remain unknown. The presented study therefore aimed to identify such elements., Methods: This study included 208 consecutive patients with RA (RA group) and 205 age- and sex-matched healthy volunteers (controls) from the prospective "TOMORROW" cohort study that has been ongoing since 2010 were included in this study. Food and nutrient intake was assessed using the brief self-administered diet history questionnaire (BDHQ), Mediterranean diet scores were calculated based on intake by controls and disease activity was determined from disease activity scores in 28 joints and erythrocyte sedimentation rates (DAS28-ESR)., Results: Intake of monounsaturated fatty acids (MUFA) was significantly lower in the RA, than in the control group (P = 0.003) and the ratio of consumed monounsaturated to saturated fatty acid (MUFA/SFA) significantly differed within the RA group after being sub-classified according to DAS28-ESR. Moreover, DAS28-ESR significantly correlated with MUFA/SFA intake after age adjustment (R = -0.228, P < 0.01). Logistic regression analysis selected high MUFA intake as an independent predictor of remission in the RA group with borderline boundary significance (odds ratio, 1.97; 95% CI, 0.98-3.98; P = 0.057). Changes in DAS28-ESR between 2010 and 2011 significantly correlated with MUFA/SFA intake after age adjustment (R = 0.180, P = 0.01)., Conclusions: Daily MUFA intake, a component of the Mediterranean diet score, might suppress disease activity in RA patients., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied., Methods: This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed., Results: Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis., Conclusion: BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA., Trial Registration: [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ , UMIN000003876].

Aim: Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA., Method: This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1.1 mm. Severity of plaque was assessed by plaque score, defined as the sum of the maximal thickness of all plaques in bilateral carotid arteries., Results: Data were analyzed from 200 patients with RA and 202 controls. Carotid plaque was observed more frequently in patients with RA than controls (47.0 vs. 36.1%, P = 0.027). Moreover, plaque score was significantly higher in RA patients (P = 0.032). In logistic regression analysis, RA represented an independent risk factor for the presence of plaque (adjusted odds ratio, 1.68; 95% confidence interval, 1.03-2.74). Comparing RA patients with and without plaque, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer was significantly higher in patients with plaque (315.8 ± 454.1 U/mL) than in patients without (165.7 ± 281.1 U/mL; P = 0.005). Moreover, multiple linear regression analysis clarified that anti-CCP antibody titer was associated with plaque score in patients with RA., Conclusion: High prevalence of any carotid plaques and severe carotid plaques were more frequent in patients with RA. High titer of anti-CCP antibodies represented a risk factor for severe carotid atherosclerotic plaque in patients with RA., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight control of disease activity might have a positive effect on bone metabolism. We aimed to determine whether bisphosphonate use is still important to improve bone mineral density (BMD) in RA patients whose disease activity was tightly controlled and the dose of glucocorticoid was reduced. This study was a sub-analysis of the 10-year prospective cohort TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW which started from 2010. We compared BMD between 192 patients with RA and age- and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray absorptiometry (DXA) in whole body mode. We then determined ratios of changes in BMD (%ΔBMD) to assess factors influencing increases in BMD among the patients using multivariate logistic regression analysis. The BMD was significantly lower in the patients than in the controls at all sites surveyed during 2010 and 2013. The %ΔBMD of the total spine was significantly higher among the patients treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001). Multivariate logistic regression analysis revealed that use of bisphosphonate was a significant factor contributing to BMD increase (odds ratio 2.13; 95% confidence interval, 1.03-4.38, P = 0.041). Meanwhile, use of biologic agents, reducing glucocorticoid dose, and control of disease activity were not significant factors for gain of BMD. The BMD was lower among patients with RA than non-RA controls. Use of bisphosphonate significantly increased the BMD of the spine in patients over a period of 3 years and was important for maintaining the BMD among patients with RA under the control of inflammation and disease activity.

Objectives: Osteoporosis is one of the complications in patients with rheumatoid arthritis (RA). In this study, we researched the morbidity of existing vertebral fractures and the risk factors for vertebral fractures in patients with RA., Methods: This study included 413 participants, 208 patients with RA, and 205 age- and sex-matched controls without RA. Clinical data, radiographic assessment of vertebral fracture from T4 to L4 in thoracic and lumber spine, bone mineral density (BMD), and bone metabolic markers (BMM) were analyzed., Results: Vertebral fractures were observed more frequently, severe and multiple in patients with RA. In the logistic regression analysis, age (adjusted odds ratios (OR): 1.07, 95% confidence interval (CI): 1.04-1.09) and RA (adjusted OR: 1.72, 95% CI: 1.04-2.83) were risk factors for existing vertebral fracture. Moreover, two bone matrix-related markers, undercarboxylated osteocalcin (ucOC) (adjusted OR: 1.68, 95% CI: 1.02-2.78), and urinary pentocidine (adjusted OR: 2.51, 95% CI: 1.48-4.24) were associated with existing vertebral fracture., Conclusions: High frequent, multiple, and severe vertebral fractures were found in patients with RA compared to the controls. Low bone quality might be the cause of the frequent prevalence of vertebral fracture in patients with RA.

Objective: Patients with rheumatoid arthritis (RA) have been recognized to experience falls frequently due to functional disabilities. The aim of this study was to prospectively investigate factors influencing falls in patients with RA compared to controls., Methods: We compared the frequency of falls in 208 RA patients and 205 age- and sex-matched volunteers for four years and analyzed risk factors for falls in RA patients using multivariate regression analysis., Results: No significant difference in the incidence rate of falls (/person-year) between patients with RA (median [interquartile range]: 0 [0, 0.5]) and controls (0 [0, 0.5]) was evident during four years. Logistic regression analysis identified age, sex, body mass index, history of falls, and lower limb implant at baseline as significant risk factors for falls. The highest quartile of anti-CCP antibody level (>300.6 U/ml) was the strongest predictor for multiple falls (odds ratio, 2.97; 95% confidence interval, 1.12-7.91, p = 0.029) among RA patients., Conclusion: During four years we could not observe the higher incidence rate of falls in RA patients compared to controls in our cohort. Subjects with a higher titer of anti-CCP antibody might be at higher risk of frequent falls among RA patients.

Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P = 0.045), prolonged surgery (OR, 1.02; P = 0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P = 0.003). Those for delayed wound healing were advanced age (OR, 1.16; P = 0.001), prolonged surgery (OR, 1.02; P = 0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P = 0.02), and foot surgery (OR, 6.60; P = 0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing.

Objectives: The deformed rheumatoid forefoot may be treated with resection of lesser metatarsal heads combined with arthrodesis or resection of the first metatarsophalangeal joint. Recurrent hallux valgus deformity has been reported by resection. We performed a prospective, randomized, internal-controlled study to compare results between arthrodesis and resection., Methods: We resected the lesser metatarsal heads bilaterally and performed arthrodesis of the first metatarsophalangeal joint on one side and resection on the opposite side. We investigated 26 patients (52 feet) who were followed at least one year. Patients were assessed for clinical score, hallux valgus angle (HVA), angle between first and second metatarsals, and angle between first and fifth metatarsals preoperatively, postoperatively and at final follow-up. We evaluated callosities, claw toes, recurrences, and procedure preferences., Results: The mean follow-up period was 4.1 years. No significant differences between arthrodesis and resection were seen, with the exception of HVA. That was significantly less on arthrodesis side (11.5°) than on resection side (17.0°, p < 0.05). Seven callosities on resection side and four on arthrodesis side were observed. On resection side, hallux valgus deformity often recurred (15.3%). Patients expressed a significant preference for arthrodesis over resection (p = 0.008)., Conclusions: Arthrodesis provides better results for maintaining HVA.

Objectives: The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level., Methods: A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay., Results: Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate., Conclusions: Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.

Objectives: Cervical spine instability (CSI) is commonly involved in patients with rheumatoid arthritis (RA). Although the treatment for RA has dramatically changed due to methotrexate and biologics, it is unclear whether this change contributes to the prevalence of CSI or not. Our objectives were to update the current prevalence of CSI and to investigate the factors associated with CSI., Methods: A cross-sectional study of patients with RA was conducted in our outpatient clinic. Clinical information and symptoms related to CSI were obtained. Plain radiography and magnetic resonance imaging were performed. CSI included atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS)., Results: Two hundred and twenty patients were analyzed, 93 (42%) of whom had CSI. A ≥ 10-year disease duration, Steinbrocker stage III, and three or more narrowed disc spaces from C2/3 to C6/7 were significantly associated with CSI. A neck pain VAS was associated with VS, but not with AAS and SAS. In contrast, methotrexate and biologics had no effect on CSI., Conclusion: The prevalence of CSI in this study was lower compared to previous reports before the approval of biologic, although we failed to detect the effect of biologics. Further prospective studies are needed to elucidate the efficacy.

We investigated the effects of biologics for rheumatoid arthritis (RA) patients on bone mineral density (BMD) and bone metabolic markers (BMM), retrospectively, and also clarified the effects of bisphosphonates (alendronate or risedronate 35 mg/week) and glucocorticoids. Participants in this study comprised 219 patients with RA, including 117 patients treated with biologics (infliximab, n = 90; etanercept, n = 27) and 102 patients with conventional disease-modifying anti-rheumatic drugs (DMARDs) for 1 year. Changes in BMD at the lumbar spine and total hip and BMMs [urinary type I collagen cross-linked N-telopeptide (NTX) and bone-specific alkaline phosphatase] were measured. BMD of the lumbar spine in both groups and total hip BMD in the biologics group were unchanged during treatment with biologics. However, BMD of the total hip was significantly decreased in the DMARDs group (from 0.731 ± 0.135 to 0.706 ± 0.135 g/cm2). Patients receiving glucocorticoids without bisphosphonates showed significant decrease in BMD of the total hip compared with patients not receiving glucocorticoids or receiving glucocorticoids with bisphosphonates in both biologics and DMARDs groups. Furthermore, BMD of the lumbar spine increased (p < 0.05) for patients in the biologics group who received bisphosphonates. NTX was significantly decreased only in the biologics group. Multiple regression analysis showed that BMD and bone metabolic marker levels correlated positively with bisphosphonate and biologics use and negatively with glucocorticoid use. BMD of the total hip was maintained in the patients using biologics without glucocorticoids or with bisphosphonates, but it was not maintained in the DMARDs patients, even without glucocorticoids or with bisphosphonates. Even if biologics have protective effect against bone loss of RA patients, we should consider reducing the dose of glucocorticoids and adding bisphosphonates for the treatment of osteoporosis.

Study Design: A cross-sectional study., Objective: This study was aimed to quantify the extent of lumbar endplate and facet joint erosion in patients with rheumatoid arthritis (RA) using magnetic resonance imaging, to calculate the prevalence of erosion, and sought correlated factors., Summary of Background Data: Few studies have examined the lumbar spine in RA, especially the relationship between endplate and facet joint erosions and lumbar lesions induced by RA., Methods: A total of 201 patients with RA were enrolled. Lumbar endplate and facet joint erosion were defined as irregularities and low-intensity change on magnetic resonance imaging, and graded utilizing the Rheumatoid Arthritis Magnetic Resonance Imaging Score. Lumbar lesions were defined as scoliosis, spondylolisthesis, and vertebral fracture on plain x-ray. Multivariable logistic regression analysis was used to seek correlations between the erosion and spinal level, RA-related factors and x-ray findings., Results: Lumbar endplate and facet erosion were detected in 70.6% and 76.6% of individuals, respectively, and at 33.8% and 38.7% of lumbar intervertebral levels, respectively. The severity of erosion in individual patients correlated with lumbar lesions. Endplate and facet erosion at each level correlated with high disease activity, and were most common at mid-lumbar and lower-lumbar levels. Strong correlations were observed between endplate erosion and adjacent vertebral body fracture or disk degeneration, and between facet erosion and spondylolisthesis., Conclusions: Lumbar endplate and facet erosion are common in RA, and are observed more frequently at mid-low levels and when RA is poorly controlled. This pattern of erosion may play a crucial role in the generation of lumbar lesions in RA.

Objective: To evaluate the prevention of joint destruction and clinical efficacy of low-dose etanercept (ETN) (25 mg/week) compared with standard-dose ETN (50 mg/week) in RA., Methods: In this prospective, randomized, open-label study, 70 patients were assigned to receive ETN at either 50 or 25 mg/week for 52 weeks. The primary endpoint was the variation in modified total Sharp score (mTSS), and secondary endpoints were variations in disease activity score in 28 joints (DAS-28), modified HAQ and adverse event rate. Values of mTSS were calculated at baseline and after 52 weeks. Non-progression was estimated as ΔmTSS ≤0.5, and the non-progression rate was compared between groups., Results: Mean values at baseline were as follows: disease duration 9.2 years; DAS-28 5.45; and annual progression of mTSS 26.1. No significant differences in background were seen between groups. At 52 weeks, the non-progression rate was significantly less in the 25 mg/week group (36.7%) than in the 50 mg/week group (67.7%) (P = 0.041). Mean ΔmTSS was higher at 25 mg/week (1.03) than at 50 mg/week (-0.13). DAS-28 was significantly improved at 4 weeks, and the effect of treatment lasted for 52 weeks in both groups. No differences in adverse event rates were seen between groups., Conclusion: Low-dose ETN is not inferior to standard-dose ETN in terms of effects on clinical manifestations. However, in terms of the radiographic non-progression rate, the effects of low-dose ETN may be inferior to the effects of standard-dose ETN., Trial Registration: UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000001798.

Background: Screening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1 year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA., Methods: This was a prospective non-randomized, non-controlled study. We enrolled 50 patients with RA who had antibodies against hepatitis B core antigen (anti-HBc) and who had started treatment with disease-modifying anti-rheumatic drugs, including those who had additionally received anti-tumor necrosis factor-α (anti-TNF-α). HBV DNA levels were measured every 2-3 months by a real-time, polymerase chain reaction-based method. Entecavir was administered to patients with HBV DNA levels >2.1 log/ml., Results: The mean observation period was 23 months (range 12-32 months). HBV reactivation occurred in 2 of 5 patients with HBV surface antigen (HBsAg) and in 1 of 45 patients without HBsAg. In patients who received anti-TNF-α therapy, antibodies against HBsAg decreased significantly. Entecavir therapy inhibited HBV amplification and prevented HBV-associated flares of hepatitis., Conclusions: The incidence of HBV reactivation was low in RA patients in whom HBV infection had been resolved. Screening for HBV reactivation and prophylactic therapy with entecavir were effective means of preventing HBV-associated hepatic failure in patients with HBsAg, as well as in those with only anti-HBc who received immunosuppressive therapy for RA.

Pyoderma gangrenosum (PG) is characterized by ulcerative skin lesions. Infliximab (IFX) may promote PG healing in patients with inflammatory bowel disease, but whether IFX is effective for treating PG in patients with rheumatoid arthritis (RA) has not reported. We report the case of a 53-year-old woman with PG complicated by RA who was treated using IFX therapy. This case suggests that IFX therapy might offer effective treatment for such patients.