Search

Objectives: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults. Methods: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. Conclusions: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired. [ABSTRACT FROM AUTHOR]

Objectives We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. Methods Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. Results We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). Conclusion Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA. [ABSTRACT FROM AUTHOR]

Objectives: To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. Methods: We enrolled patients with RA ≥18years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. Results: The mean age of the 2614 patients was 62.4years; 85.1 % were female. Median values of the WPAI-RA score were 1.1 % for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1 %), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). Conclusions: The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). Methods: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. Results: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. Conclusions: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA. [ABSTRACT FROM AUTHOR]

Objectives To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. Material and methods A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features. Results In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of Δ SHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model. Conclusion A high-performance scoring model for SHS that is applicable to clinical research was constructed. [ABSTRACT FROM AUTHOR]

Objectives. To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. Methods. We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. Results. We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. Conclusions. Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the cost-effectiveness of tocilizumab in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. Methods. The cost-effectiveness was determined using a Markov model-based probabilistic simulation. Data from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study between April 2007 and April 2011 were extracted using a pair-matching method: tocilizumab group (n = 104), patients who used at least 1 disease-modifying anti- rheumatic drug and in whom tocilizumab treatment was initiated; methotrexate group (n = 104), patients in whom methotrexate treatment was initiated for the first time or after an interruption of 6 or more months. Assuming a 6-month cycle length, health benefits and costs were measured over a lifetime and discounted at an annual rate of 3%. Results. Compared with methotrexate treatment, lifetime costs and quality-adjusted life years (QALYs) for tocilizumab treatment were approximately 1.5- and 1.3-times higher, respectively. Incremental cost per QALY gained with tocilizumab was $49,359, which was below the assumed cost-effectiveness threshold of $50,000 per QALY. The probability of tocilizumab being cost- effective was 62.2%. Conclusion. The simulation model using real-world data from Japan showed that tocilizumab (at a certain price) may improve treatment cost-effectiveness in patients with moderate-to-severe RA by enhancing quality-adjusted life expectancy. [ABSTRACT FROM AUTHOR]

Background/Purpose. The use of biologic disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) has been increasing since 2003. In this study, we evaluated changes in the characteristics of patients receiving biologic DMARDs daily, in Japan. Methods. The characteristics of all RA patients who received any biologic DMARD at the Institute of Rheumatology, Tokyo Women's Medical University, within 1 year after its approval in Japan, were retrospectively evaluated. The periods of patient enrollment for each biologic agent were: infliximab (IFX), 2003-2004; etanercept (ETN), 2005-2006; tocilizumab (TCZ), 2008-2009; adalimumab (ADA), 2008-2009; abatacept (ABT), 2010-2011; and golimumab (GLM), 2011-2012. We retrospectively collected individual patient characteristics, concomitant medication usage, and disease activity assessed by disease activity score 28 (DAS28) at the time of administration, from the medical records. The retention rate for each agent at 6 months after treatment initiation was also assessed. Results. The numbers of patients who received each biologic DMARD at our institute within 1 year after its approval were: IFX, 49; ETN, 50; TCZ, 62; ADA, 52; ABT, 40; and GLM, 77. From 2003 to 2012, the proportion of patients with prior use of any biologic DMARD increased, as did concomitant use and dose of methotrexate (MTX); however, corticosteroid use and doses decreased. DAS28, at the time of treatment initiation, gradually decreased. At the time of IFX administration, 75% and 25% of patients had high and moderate disease activity respectively, compared to 25% and 58% respectively, of patients who received GLM. No significant difference was observed in the retention rate of biologic DMARDs at 6 months (range, 75.0% to 89.6%). Conclusion. Baseline disease activity of RA patients who received biologic DMARDs between 2003 and 2012 has changed from high to moderate in daily practice in Japan. [ABSTRACT FROM AUTHOR]

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 (3.9 ± 1.3 for onset in the 1960s vs. 2.2 ± 1.1 for onset in the 2000s, p = 0.04). The percentage of patients requiring orthopedic surgery has decreased (53.8% before the 1970s vs. 10.0% in the 2000s). Conclusion. Patients with more recent disease onset showed an improved outcome. Establishing and sharing a transition program among pediatric and non-pediatric rheumatologists is desirable. [ABSTRACT FROM AUTHOR]

Objective. To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice. Methods. We performed a retrospective study of 137 RA patients who were treated with abatacept for 24 weeks between October 2010 and June 2011 at four rheumatology centers in Japan. Outcomes were compared between biologic-naïve and biologic-experienced patients. Disease activity was assessed using the Simplified Disease Activity Index (SDAI) and the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). Results. The retention rate of abatacept at 24 weeks was 79.6%. SDAI (from 24.6 ± 12.5 to 12.9 ± 11.6) and DAS28-ESR (from 5.2 ± 1.4 to 3.9 ± 1.4) decreased significantly from baseline to Week 24 (both P < 0.001). Remission/low disease activity were achieved in 2.2%/11.2% (SDAI) and in 5.3%/2.3% (DAS28-ESR). The change in SDAI and the remission/low disease activity rates at Week 24 was greater in biologic-naïve patients than in biologic-experienced patients. Structural remission (van der Heijde-modified total Sharp score ≤ 0.5) was achieved by 63.4% of patients. Conclusions. The present results confirm that abatacept is effective in routine clinical practice and support its use as the first-line biologic agent in patients. [ABSTRACT FROM AUTHOR]

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

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

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

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

We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles −0.9 to 2.0) at week 52 ( P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice. [ABSTRACT FROM AUTHOR]

The treatment of rheumatoid arthritis (RA) has improved dramatically with the advent of the latest generation of disease-modifying antirheumatic drugs. Despite these advances, in some patients inflammation is not diminished sufficiently to prevent irreversible musculoskeletal damage, thereby necessitating surgical intervention to reduce pain and improve function. For RA treatment, Japanese orthopedic surgeons also prescribe medication. In this study, we examined whether this Japanese system is effective for RA treatment. We analyzed the clinical condition of RA patients treated by rheumatologists and those treated by orthopedists in a linked registry study using information from a large observational cohort of RA patients followed every half year from 2000 to 2010 (the IORRA cohort). Two groups of patients were compared: patients treated by rheumatologists (rheumatologic group) and patients treated by orthopedists (orthopedic group). The results revealed that patients in the orthopedic group were older, more likely to be female, and had a longer disease duration than patients in the rheumatologic group. The proportion of patients with a history of joint surgery was also much higher in the orthopedic group than in the rheumatologic group. The average scores on the Japanese version of the Health Assessment Questionnaire, and the remission ratio determined using a Boolean-based definition gradually increased from 2000 until 2010, and these findings were consistently better in the rheumatologic group than in the orthopedic group. These data suggest that patients treated primarily by orthopedists are more likely to have long-standing RA compared to patients treated by rheumatologists. Therefore, it is critical for rheumatologists and orthopedists to complement each other medically in the treatment of RA patients. [ABSTRACT FROM AUTHOR]

We aimed to demonstrate the incidence of serious respiratory infections in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy. We analyzed the incidence of serious respiratory infections in 601 RA patients enrolled in TCZ clinical trials and their extension studies (TCZ cohort) and in 601 age- and sex-standardized RA patients treated in daily clinical practice at Tokyo Women's Medical University (IORRA subsample cohort). The rates of serious respiratory infections were 1.77 per 100 patient-years from 1999 to 2008 in the TCZ cohort and 0.53 per 100 patient-years from 2000 to 2009 in the IORRA subsample cohort. With the IORRA subsample cohort regarded as a standard population, the standardized incidence ratio (SIR) of serious respiratory infection in the TCZ cohort was 3.64 [95% confidence interval (CI) 2.56-5.01], standardized for age and sex; 2.35 (95% CI 1.66-3.24), standardized for age sex, and corticosteroid use; 1.85 (95% CI 1.30-2.55), standardized for age sex, and pre-existing pulmonary involvement; and 2.41 (95% CI 1.68-3.34) standardized for age sex, and disease activity. The risk of serious respiratory infection in the TCZ cohort was approximately double that in the IORRA subsample cohort after standardizing for corticosteroid use, pre-existing pulmonary involvement, or disease activity. This is comparable to the risk reported when tumor necrosis factor (TNF) inhibitors are used. [ABSTRACT FROM AUTHOR]

The maximum dosage of methotrexate (MTX) for treatment of rheumatoid arthritis (RA) formally approved in Japan is 8 mg/week. We intended to examine the efficacy and safety of MTX at dosages over 8 mg/week in Japanese rheumatoid arthritis patients using the large Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort database. Among 9,122 patients registered in the IORRA database from the October 2000 survey to the October 2007 survey, 5,201 patients who had been treated with MTX were selected. We attempted to overcome the drawbacks innate to nonrandomized studies by using longitudinal analyses and multifactorial logistic regression analyses. Cross-sectional analysis of data obtained from the October 2007 survey indicated that dosages of MTX higher than 8 mg/week were used in 27.5% of patients treated with MTX. Longitudinal analyses based on data from three consecutive phases showed that final Disease Activity Score-28 (DAS28) values were significantly lower [ n = 260, mean difference 0.563, 95% confidence interval (CI) 0.438-0.688, P < 2.2 × 10, two-sided paired t test] than initial values when MTX was increased from 8 mg/week or lower to over 8 mg/week. In addition, longitudinal analyses based on data from two consecutive phases indicated decreases in DAS28 values of 0.26 ± 1.04 ( n = 690, P = 6.78 × 10, two-sided paired t test) when MTX dosages were increased from 8 mg/week or lower to over 8 mg/week, compared with decreases of 0.07 ± 0.89 ( n = 2,125, P = 0.000307) when the dosage was maintained at 8 mg/week. The decreases in DAS28 values were significantly larger in the former than the latter ( P = 2.27 × 10, two-sided unpaired t test). Concerning safety of MTX at dosages over 8 mg/week, we performed logistic regression analysis in which the objective variable was the existence or nonexistence of self-reported side-effects and the explanatory variable was the MTX dosage in the former phase, with adjustments made for age, sex, body mass index (BMI), steroid administration, folic acid administration, concomitant pulmonary diseases, and renal dysfunction. The results indicated that MTX dosages over 8 mg/week did not have any association with either severe or severe + moderate side-effects. These data regarding both efficacy and safety of MTX at dosages over 8 mg/week in Japanese RA patients would provide the basis for use of the drug at dosages currently not formally approved by the Japanese government. [ABSTRACT FROM AUTHOR]

We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher's exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort ( p < 0.001) and from 4.1 to 3.1 in the 2006-cohort ( p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 ( p < 0.02) in the 2001-cohort and from 0.71 to 0.41 ( p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort ( p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a noteworthy condition in the treatment of systemic sclerosis (SSc) because of its associated mortality and morbidity; however, the efficacy of various treatments for ILD has been controversial in previous reports. In this study, we examined the efficacy and safety of intravenous cyclophosphamide (IVCY) pulse therapy with prednisolone (PSL) for the treatment of ILD with SSc. A total of 121 patients with SSc were screened and evaluated for ILD, using high-resolution computed tomography of the chest, pulmonary function testing, and bronchoalveolar lavage. Thirteen patients with active ILD were enrolled in this study. The treatment protocol for ILD was 0.4 g/m of body surface area of IVCY monthly plus 0.8 mg/kg of body weight of PSL daily. Two to six doses of IVCY were administered, depending on the remission of ILD. Initial PSL doses were maintained for a month and then gradually tapered to 10 mg daily. An activity index of ILD showed improvements in all patients in the 12 months after the initial intervention; however, four patients experienced recurrence of ILD after 24 months, and one additional patient had recurrence of ILD after 36 months. Seven patients reached the 48-month point with no recurrence of ILD. This long observational study for 48 months showed the efficacy of IVCY with PSL for active alveolitis in the first year. However, because five patients had recurrence of ILD more than 1 year after the treatment, it would be necessary to consider maintenance therapy for ILD beyond 1 year. [ABSTRACT FROM AUTHOR]

Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan. The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004. Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed. The average outpatient cost gradually increased (+7.7% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004. Medications accounted for approximately 50% of total outpatient costs, which increased 29.6% during the 4 years. The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score. Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs ( p < 0.001). Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan. Medical costs were higher with increasing RA disease activity and disability levels. [ABSTRACT FROM AUTHOR]

The objective of this study was to show whether the disease activity of rheumatoid arthritis (RA) patients had improved in Japan, and whether the improvement of disease activity had resulted in a better outcome of patients. In a single-institute-based prospective observational cohort of RA patients (Institute of Rheumatology, Rheumatoid Arthritis, IORRA), a total of 7512 patients were enrolled, and their information was collected biannually. A cross-sectional data set A that included all patients in each phase was analyzed. From October 2000 to April 2006, disease activity score DAS28 significantly improved from 4.15 to 3.63, and the frequency of patients in remission (DAS28 < 2.6) increased from 8.5% to 21.5%. During this period, the frequency of methotrexate users increased from 33.9% to 58.7% and the average dosage of methotrexate also increased from 5.59 mg/week to 6.94 mg/week; on the other hand, there was no increase in any adverse reaction among the methotrexate users. To investigate the relationship between longitudinal disease control and progression of disability, a longitudinal data set B that included 712 patients who completed all phases of the study from 2000 to 2006 was selected and was analyzed. The disability index JHAQ of a poorly controlled group (average DAS > 5.1) increased (+34.8%), that of a moderately controlled group (average DAS 3.2–5.1) also increased (+14.0%), but that of a well-controlled group (average DAS < 3.2) decreased (–13.0%). In conclusion, by using a prospective observational cohort IORRA in Japan, we demonstrate that RA disease activity improved from 2000 to 2006, which correlates with an increased use of methotrexate. The suppression of disease activity resulted in a better outcome for patients. [ABSTRACT FROM AUTHOR]

We evaluated the effects of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on endoscopic and histological findings in patients with rheumatoid arthritis (RA) before and after the eradication of Helicobacter pylori infection. Helicobacter pylori ( H. pylori) eradication using lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week was conducted in 44 patients (mean age: 56.5 years) with RA. Using the updated Sydney system, endoscopic and histological findings of the greater curvature of the antrum, the greater curvature of the upper corpus, and the lesser curvature of the lower corpus were compared before and after eradication, for a mean follow-up period of 3.5 months. Overall, H. pylori eradication was successful in 32 patients (72.7%). Of these 32 patients, 23 were NSAID users. In the successful eradication group, (1) there was no significant change on endoscopic findings, including gastric erythema and erosion in all three regions irrespective of NSAIDs use; (2) of 17 active ulcers before eradication in NSAIDs users, all healed except for one duodenal ulcer that persisted, where one patient newly developed a gastric ulcer, one developed erosive duodenitis, and two developed reflux esophagitis, all in NSAID users; (3) neutrophil infiltration and chronic inflammation were significantly improved in all three regions after H. pylori eradication irrespective of use of NSAIDs, while atrophic change and intestinal metaplasia did not change. In the eradication failure group; (1) there was no significant change on endoscopic and histological findings in the three regions; (2) two of three ulcers present before eradication on NSAID users persisted even after eradication, and no new cases of gastric ulcer or erosive duodenitis occurred. In conclusion, over a mean follow-up period of 3.5 months, use of NSAIDs in Japanese patients with RA did not impair the healing process of gastric and duodenal ulcers nor did it affect the endoscopic and histological improvements associated with H. pylori eradication. [ABSTRACT FROM AUTHOR]

The optimal methotrexate dose differs between rheumatoid arthritis (RA) patients, and dose-escalation strategies also differ among rheumatologists. By taking advantage of the heterogeneous methotrexate dosing that occurs among Japanese rheumatologists, we analyzed the efficacy and safety of different methotrexate doses. A large observational cohort of RA patients, IORRA, was established in 2000. A dataset from April 2003 that included 4578 RA patients was used for a cross-sectional analysis, while a dataset of 1649 patients who received methotrexate from October 2000 to October 2005 was used for a longitudinal analysis. The cross-sectional analysis included 12 rheumatologists who prescribed methotrexate to more than 60 patients. Mean methotrexate dose ranged widely (4.8–9.0 mg/week) among rheumatologists with a significant positive relationship between average methotrexate dose and the percentage of patients with Disease Activity in 28 Joints (DAS28) scores below 3.2. During the longitudinal analysis, both methotrexate prescription frequency and the average dose prescribed by 16 rheumatologists increased. Overall disease activity as assessed by DAS28-area under the curve (AUC) and disability progression as assessed by Japanese version of the Health Assessment Questionnaire (JHAQ)-slope inversely correlated with the extent of methotrexate use. This study demonstrated that extensive methotrexate use effectively suppressed RA disease activity and inhibits disability progression. In addition, we have found that it is critical to pay attention to patient-reported adverse reactions. [ABSTRACT FROM AUTHOR]

We investigated the prevalence and predictors of complementary and alternative medicine (CAM) use by patients with rheumatoid arthritis (RA) in Japan. A cross-sectional descriptive study was performed using the database from a large observational cohort of RA patients in the Institute of Rheumatology, Tokyo Women's Medical University. Logistic regression analysis was carried out to reveal predictive factors for CAM use. Among 3815 RA patients, 1321 (34.6%; 174 males, 1147 females) used at least one type of CAM. Health foods, including dietary supplements, were the most commonly used. CAM was more frequently used by female patients (odds ratio: 0.578; 95% confidence interval [CI] = 0.451–0.740). A multiple logistic regression analysis revealed that sex (odds ratio: 0.489; 95% CI = 0.333–0.718) and degree of satisfaction with disease-modifying antirheumatic drugs (DMARDs) (odds ratio: 0.899; 95% CI = 0.852–0.948) were significant independent predictive factors for CAM use. The serum C-reactive protein level and erythrocyte sedimentation rate showed no significant associations with CAM use. Approximately 35% of RA patients used CAM in Japan. Female patients and patients dissatisfied with DMARDs used CAM more frequently, regardless of their disease activity. [ABSTRACT FROM AUTHOR]

This report documents the results of a study performed to examine clinical use of mizoribine (MZR), using data from a large-scale prospective cohort study, IORRA (Institute of Rheumatology Rheumatoid Arthritis). The number of patients with RA entered in this study from October 2000 through October 2003 was 6238. Three hundred and six patients (4.9%) received MZR therapy. Mizoribine users who were taking methotrexate (MTX) (MTX–MZR group, n = 94) and over 70 years of age (elderly group, n = 45) were collected. Cumulative retention rates of MZR were calculated by Kaplan–Meier analysis. Median drug survival of MZR was 28 months for the poor responders to MTX and 43 months for the poor responders to MZR, with no significant difference between these groups. Cumulative retention rate of MZR in the elderly group did not show a significant difference compared to that in patients aged under 70 years. Ten patients (10.6%) in the MTX–MZR group and 10 patients (22.2%) in the elderly group experienced adverse effects of MZR. None of these adverse effects was serious. This study indicated that, although MZR has not been frequently prescribed for RA patients, it may be useful and relatively safe for patients who are poor responders to MTX as an additional regimen to MTX therapy as well as for elderly patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify “depressed patients.” A total of 1875 (41.1%) were identified as “depressed patients” who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index ( P < 0.0001) and patient's VAS for general health ( P < 0.0001) were also strongly and significantly associated to the response variable “probability of depressed patients.” Patient appraisal of poor general health and greater disability were associated with depressed mood in RA. [ABSTRACT FROM AUTHOR]

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58–0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori−/NSAID− group, 1.24% in the H. pylori−/NSAID+ group, 1.06% in the H. pylori+/NSAID− group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19–7.38) and 4.31 (95% CI: 0.57–32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA. [ABSTRACT FROM AUTHOR]

In general, patients with systemic sclerosis (SSc) have been classified in two clinical subsets (diffuse and limited) based on the extent of skin thickening, and the extent of skin fibrosis is closely related to the severity of organ involvement and mortality rates. In addition, there is a rapid progression of skin thickening in diffuse cutaneous SSc (dcSSc). In this study, we classified a novel subset of SSc based on the rate of skin thickening progression, and evaluated the relationship of the subset to disease severity and laboratory markers. Thirty-three patients with dcSSc were included in the study. Participants who had a modified Rodnan’s total skin thickness score higher than 15 points within a year from the first symptoms were defined as having rapidly progressive SSc (RPSSc; group 1), while all the other dcSSc patients were defined as having non-RPSSc (group 2). The frequencies of interstitial lung disease and renal crisis were significantly higher in group 1 than in group 2. The frequencies of antitopoisomerase I antibody (anti-topo I) and anti-SS-A antibody were significantly higher in group 1 than in group 2. Conversely, the frequency of anticentromere antibody was significantly higher in group 2 than in group 1. This study demonstrates the clinical significance of a new subset of SSc (defined as RPSSc), which is characterized by a markedly rapid progression of skin thickening. This new classification may be useful for predicting the prognosis of SSc at an early stage, so that patients who should receive aggressive therapy with immunosuppressants might be identified. [ABSTRACT FROM AUTHOR]

Background Brain metastases (BM) from esophageal cancer (EC) are rare. Despite of an advance of treatments for the patients with BM from EC, life expectancy and quality of life of these patients are still poor. We present an overview of the patients with BM from EC at a single institute. Methods We retrospectively identified 10 patients with BM from EC treated with surgery, radiation, or a combination of multidisciplinary therapies at Osaka National Hospital between 2003 and 2017 for stages IIb through IV of primary EC (follow-up, > 157 days). Medical records were reviewed to collect demographic and clinical information. Results Median age at diagnosis of BM was 63.5 years (range, 53–79 years). 9 patients were male, and 7 patients had squamous cell carcinoma of EC at the primary esophageal resection. Median overall survival from the commencements of therapy for BM was 156 days (range, 17–5404 days). The interval between the primary esophagectomy and the start of therapy for BM from EC was 298 days (range, 64–860 days). The average score of Karnofsky performance status (KPS) just before a diagnosis of BM was 75 (range, 50–90). On univariate analysis, the patients with the lower score of KPS (P  = 0.01) or the shorter interval between the primary esophageal surgery and the start of therapy for BM (P  = 0.06) were found to have worsened survival after the therapy for BM from EC. Conclusion The patients who had a poor KPS just before a diagnosis of BM, or the shorter interval between the esophagectomy for the primary EC and the start of therapy for BM, had poor prognosis. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]