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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. [ABSTRACT FROM AUTHOR]

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 receiveroperating 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 &leq;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. [ABSTRACT FROM PUBLISHER]

The general disease activity of patients with rheumatoid arthritis (RA) is well controlled by disease-modifying antirheumatic drugs, but local inflammation often remains in a few small joints. Electroporation, making small pores in cell membranes, has proven useful for drug delivery. The safety of a combination therapy of methotrexate (MTX) and electroporation for local joint inflammation in RA was investigated in a prospective, randomized, double-blind, placebo-controlled, exploratory study (UMIN000016606). The patients were randomly allocated to groups receiving a combination of MTX and electroporation (True-EP) and MTX alone (False-EP) groups. The MTX solution was injected into finger joints under ultrasound guidance. The True-EP group underwent electroporation with MTX, and the False-EP group was given MTX but only pinched using the electrode. The ultrasound grade, disease activity, and safety were evaluated from baseline to 26 weeks. Five patients (3 True-EP and 2 False-EP) with a mean age of 57.4 years and disease duration of 10.2 years were enrolled. The grey-scale grade was unchanged in 3 cases (2 True-EP and 1 False-EP) and increased in 2 cases (1 True-EP and 1 False-EP). Disease activity was alleviated in 3 cases (2 True-EP and 1 False-EP). No patients experienced burned skin or electroshock. The combination therapy of electroporation and MTX was safe for RA patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]