Institute Of Rheumatology, Rheumatoid Arthritis Cohort Research Articles

Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: results from the IORRA cohort.

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. 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. 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). 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.

Impact of concomitant chronic kidney disease on hospitalised infections and remission in patients with rheumatoid arthritis: results from the IORRA cohort.

To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to < 60; moderate CKD, eGFR ≥30 to < 45; and severe CKD, eGFR <30. We assessed the association between concomitant CKD and the occurrence of unfavourable clinical events or achieving remission during a 5-year observational period. Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07-2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12-3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68-0.99, p = .04). Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.

THU0086 FACTORS ASSOCIATED WITH TREATMENT RESPONSE IN PATIENTS WITH ELDERLY-ONSET RHEUMATOID ARTHRITIS: 3-YEAR OBSERVATION USING THE IORRA COHORT.

Background:Patients with elderly-onset rheumatoid arthritis (EORA) are on the rise in the aging or super-aging society, especially in Japan. Patients with EORA have more comorbidities than those with younger-onset RA, a higher risk of adverse drug reactions due to reduced drug metabolism, and a higher risk of infections1). Therefore, patients with EORA tend to receive suboptimal treatment, resulting in insufficient control of disease activity2). Although several studies reported treatment responsiveness in patients with EORA, many of them have a limited observation period3-8), and long-term treatment responses and their associated factors need to be clarified.Objectives:We retrospectively evaluated treatment responses of patients with EORA for 3 years and their associated factors in a clinical setting.Methods:The Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort is a large, single institute-based, observational cohort of RA patients established at Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. The subjects were RA patients who first enrolled in the IORRA cohort from 2010 to 2014, were over 60 years old with less than 1-year disease duration, and had a DAS28-ESR over 3.2 at entry. The primary endpoint was DAS28-ESR &lt;3.2 after 3-year observation. A multivariate logistic regression analysis was conducted to identify factors at baseline associated with the primary endpoint. The missing values of DAS28-ESR were imputed by using the last observation carried forward method.Results:Among a total of 250 patients in this study, 152 patients (60.8%) achieved DAS28-ESR &lt;3.2 after 3-year observation (remission/low disease activity (RL) group), and 98 patients did not (moderate/high disease activity (MH) group). Baseline characteristics of the patients were as follows (average ± SD or %): the RL group, age 69.9 ± 6.5, female 77%, DAS28-ESR 4.3 ± 0.8, J-HAQ 0.9 ± 0.7, PSL user 23.7%, MTX user 64.5%, and biologics user 4.0%; the MH group, age 69.4 ± 6.7, female 80.6%, DAS28-ESR 4.4 ± 0.8, J-HAQ 1.0 ± 0.7, PSL user 36.7%, MTX user 64.3%, and biologics user 6.1%. Proportions of the patients with cardiovascular disease and malignancy were 13.3% and 11.2% in the MH group and 5.9% and 1.3% in the RL group, respectively. DAS28-ESR and J-HAQ score after 3-year observation of the RL group were 2.3±0.5 and 0.4±0.5, respectively, and those of the MH group were 3.4±0.9 and 1.0±0.8, respectively. Corticosteroid use and having malignancy at baseline were associated with not achieving DAS28-ESR &lt;3.2 after 3-year observation using multivariate analysis (Table 1). Similar results were obtained when MTX use and corticosteroid use were replaced by the average dose of each drug.Conclusion:The majority of the patients with EORA achieved DAS28-ESR &lt;3.2 after 3-year observation, and no use of corticosteroid and absence of malignancy at baseline were associated with the good outcome.

Age and female gender associated with periodontal disease in Japanese patients with rheumatoid arthritis: Results from self-reported questionnaires from the IORRA cohort study

Objectives: This study aimed to evaluate the prevalence of, and the factors associated with, periodontal disease in Japanese patients with rheumatoid arthritis (RA).Methods: Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed three self-administered questionnaires including questions about recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and any history of periodontitis. Logistic regression analyses were used to evaluate associations with clinical variables for each questionnaire.Results: Among 5600 Japanese patients with RA, 31.0%, 18.3%, and 20.4% of patients self-reported recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and a history of periodontitis, respectively. In multivariate models, younger age, fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), and prednisolone dosage were significantly (p < .05) associated with recent gingival bleeding during toothbrushing. Older age, female gender, and ever-smoker status were significantly correlated with a recent diagnosis of periodontitis.Conclusion: Many Japanese patients with RA experience gingival bleeding during toothbrushing and are diagnosed with periodontitis. Age, female gender, ever-smoker status, fracture history, JHAQ-DI, and prednisolone dosage appeared to be associated with periodontal disease in Japanese patients with RA.

Factors associated with decreasing serum 25(OH)D among Japanese patients with rheumatoid arthritis: Results from the IORRA cohort study

Objective: The aim of this study was to investigate factors that predict a decrease in serum 25(OH)D among Japanese patients with rheumatoid arthritis (RA).Methods: In 2011 and 2013, serum 25(OH)D was evaluated in the same 2534 Japanese patients with RA (2179 women and 355 men) who participated in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort study. A vitamin D deficiency was defined as serum 25(OH)D levels <20 ng/mL. Predictive factors resulting in decreased serum 25(OH)D over a 2-year period were evaluated using multivariate logistic regression.Results: The prevalence of vitamin D deficiency was 73.3% in 2011 and 68.2% in 2013. Serum 25(OH)D levels decreased by >5 ng/mL from 2011 to 2013 in 224 (8.8%) patients. A serum 25(OH)D decrease of >5 ng/mL was significantly associated with female gender, younger age, and disuse of bisphosphonates among all patients, and younger age, higher Japanese health assessment questionnaire disability index (JHAQ-DI), increased tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 among women with RA.Conclusion: Female gender, younger age, JHAQ-DI, tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 appear to be associated with a decrease in serum 25(OH)D in Japanese patients with RA.

Reduction of methotrexate and glucocorticoids use after the introduction of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis in daily practice based on the IORRA cohort

Objectives: To evaluate usage patterns for methotrexate (MTX) and/or glucocorticoids in rheumatoid arthritis (RA) patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) in daily practice.Methods: Data from RA patients who commenced treatment with bDMARDs (infliximab [IFX], etanercept [ETN], tocilizumab [TCZ], or adalimumab [ADA]) from 2008 to 2010 were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The proportions of patients taking concomitant MTX and glucocorticoids and doses of these medications were evaluated before and 2 years after initiation of each bDMARD.Results: A total of 470 RA patients who had initiated a bDMARD (IFX: n = 98, ETN: n = 181, TCZ: n = 90, and ADA: n = 101) were evaluated. The proportion of patients taking MTX decreased over time among ETN and TCZ users, while it increased among ADA users. The MTX dose decreased over time among IFX, ETN, and TCZ users, but not among ADA users. Although the rate of glucocorticoid use and dose decreased after bDMARD initiation in all four bDMARD groups, approximately 50% of patients continued to receive glucocorticoids 2 years after bDMARD initiation.Conclusion: MTX and glucocorticoid use and doses in daily practice were commonly reduced after the initiation of bDMARDs, with the dose adjustment varied depending on the bDMARD.

Characteristics and risk factors of lymphoproliferative disorders among patients with rheumatoid arthritis concurrently treated with methotrexate: a nested case-control study of the IORRA cohort.

The purpose of the study is to demonstrate the characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA) and risk factors for LPD among RA patients concurrently treated with methotrexate (MTX). Among patients who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study in October 2010, past existence of LPD from patient's report was confirmed through medical charts. Background factors, LPD pathological findings, and the clinical courses of LPD and RA after LPD were assessed. To analyze the risk of MTX-associated LPD among RA patients concurrently treated with MTX, a nested case-control study design was used to select control patients who had received MTX but did not develop LPD by matching calendar date, sex, and age (within 5years) at a 1:10 ratio. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for occurrence of LPD were analyzed by multivariate analysis. Forty-eight patients experienced LPD among 5757 patients, and 25 (52.1%) of those had lymphoma. LPD regressed in 60.4% of all LPD patients and 24.0% of lymphoma patients. In the 26 cases who developed LPD during MTX treatment, multivariate analysis revealed that 28-joint disease activity score (DAS28) (OR 1.57 [95% CI, 1.12-1.57]; p<0.01) and lactate dehydrogenase (LDH) level (OR 1.01 [95% CI, 1.00-1.02]; p<0.01), but not concomitant dose of MTX, were risk factors for LPD. Among RA patients concomitantly treated with MTX, high disease activity, but not MTX dose, was a risk factor for the occurrence of LPD.

Profiles of EQ-5D utility scores in the daily practice of Japanese patients with rheumatoid arthritis; Analysis of the IORRA database

Objective. Along with the advances of newly developed medical therapies in rheumatoid arthritis (RA), the number of pharmacoeconomical issues has been paid attention rapidly. For cost–utility analysis and determination of quality-adjusted life years, measurement of the EuroQol 5-dimensional descriptive system (EQ-5D) is essential, and has been used in several clinical studies. However, EQ-5D utility measure in Japanese patients with RA, especially in daily practice has not been fully documented. We analyzed the distribution of EQ5D utility scores and investigated the relationship between other clinical measures based on our Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database.Method. Among 5,284 outpatients who participated in the IORRA cohort study on October 2007, data from 5,043 patients who completed the EQ-5D questionnaire were cross-sectionally analyzed. EQ-5D scores in each subgroup for baseline feature such as gender, age, disease activity score 28 (DAS28), and Japanese version of health assessment questionnaire (J-HAQ) were evaluated. For the evaluation of variables that influenced EQ-5D score, the contribution of each variable was evaluated by ANOVA.Results. Average EQ-5D score was 0.76 in 5,284 patients (84% females, average age: 59.0 years, average disease duration: 12.4 years) whose average DAS28 was 3.3 and average J-HAQ was 0.74. EQ-5D scores were highly correlated with J-HAQ and DAS28, and were significantly lower in females and rheumatoid factor-positive patients. Older age, longer disease duration, higher DAS28, and higher J-HAQ were also significantly associated with lower EQ-5D scores. In multivariate analysis, the factor that most strongly influenced EQ-5D was J-HAQ (57.6%), followed by pain visual analog score (VAS; 12.5%).Conclusion. This study clearly demonstrated the distribution of EQ-5D score in the daily practice of RA patients, and provides important information for the pharmacoeconomical studies in rheumatology.

AB0824 Improved Prediction of Hip Fracture Using the Health Assessment Questionnaire and FRAX in Japanese Patients with Rheumatoid Arhritis: A Prospective Observational Study

BackgroundThe World Health Organization Fracture Risk Assessment Tool (FRAX®) algorithm can be used to estimate 10-year probabilities of hip and major osteoporotic fractures. This tool has not yet been validated...

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

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

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

BackgroundA new strain of pandemic influenza emerged in 2009. The Infectious Disease Surveillance Center of Japan reported that almost all influenza occurring from September 2009 to April 2010 in Japan...

AB0033 Association between radiographic joint damage and a PADI4 SNP in japanese RA patients

BackgroundPeptidyl arginine deiminase, type IV (PADI4) gene has been reported to be associated with susceptibility to rheumatoid arthritis (RA) mainly in Asian populations (1, 2).ObjectivesTo investigate the impact of peptidyl...

OP0245 Sites, Frequencies, and Causes of Fractures in Patients with Rheumatoid Arthritis: A Large Prospective Observational Cohort Study in Japan

BackgroundFew studies have described in detail the fractures at all the skeletal sites in patients with rheumatoid arthritis (RA) 1). This information would be helpful for customizing strategies for preventing...

FRI0065 Clinical factors associated with the progression of functional impairment in rheumatoid arthritis patients who maintained the remission criteria defined by the new acr/eular criteria

BackgroundRemission is considered a therapeutic target in the management of patients with rheumatoid arthritis (RA). In 2010, new remission criteria were proposed by ACR/EULAR to achieve better patient outcomes. We...

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

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

Studies of the efficacy and safety of methotrexate at dosages over 8 mg/week using the IORRA cohort database

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 × 10−22, 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 × 10−11, 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 × 10−6, 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.

Studies of the efficacy and safety of methotrexate at dosages over 8 mg/week using the IORRA cohort database

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 × 10−22, 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 × 10−11, 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 × 10−6, 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.

Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis

The objective of this study was to assess the usefulness of tacrolimus (TAC) for rheumatoid arthritis (RA) patients. The first 101 consecutive RA patients in whom TAC treatment was initiated were prospectively registered and their data analyzed. Clinical variables were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The 101 patients included 85 females and 16 males. Average doses of TAC were 1.62 mg/day at entry and 2.13 mg/day at month 12. The average doses of concomitantly prescribed prednisolone (6.92 mg/day) and methotrexate (MTX; 8.59 mg/week) were higher than those in all RA patients in the IORRA cohort. At month 12, 57 patients remained on TAC therapy; 18 patients had discontinued TAC due to side effects, and 16 patients had discontinued due to inefficacy. Adverse reactions responsible for discontinuation included gastrointestinal symptoms, renal dysfunction, and infection. According to the European League Against Rheumatism (EULAR) response criteria, 56.5% of the patients who continued TAC at 12 months experienced “good” or “moderate” responses. Through the use of last observation carried forward (LOCF) methodology, the average Disease Activity Score (DAS) 28 significantly improved. We confirmed the usefulness of TAC for the treatment of RA and found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.

Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis

The objective of this study was to assess the usefulness of tacrolimus (TAC) for rheumatoid arthritis (RA) patients. The first 101 consecutive RA patients in whom TAC treatment was initiated were prospectively registered and their data analyzed. Clinical variables were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The 101 patients included 85 females and 16 males. Average doses of TAC were 1.62mg/day at entry and 2.13mg/day at month 12. The average doses of concomitantly prescribed prednisolone (6.92mg/day) and methotrexate (MTX; 8.59mg/week) were higher than those in all RA patients in the IORRA cohort. At month 12, 57 patients remained on TAC therapy; 18 patients had discontinued TAC due to side effects, and 16 patients had discontinued due to inefficacy. Adverse reactions responsible for discontinuation included gastrointestinal symptoms, renal dysfunction, and infection. According to the European League Against Rheumatism (EULAR) response criteria, 56.5% of the patients who continued TAC at 12months experienced "good" or "moderate" responses. Through the use of last observation carried forward (LOCF) methodology, the average Disease Activity Score (DAS) 28 significantly improved. We confirmed the usefulness of TAC for the treatment of RA and found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.