Japanese Rheumatoid Arthritis Research Articles

Association of rare single nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis.

Rheumatoid arthritis (RA) is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA. Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415, and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses. MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (p = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% confidence interval [CI] 2.05-55.37) or ILD (p = 0.0071, Pc = 0.0284, OR 7.33, 95%CI 1.52-35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (p = 0.0072, Pc = 0.0288, OR 29.55, 95%CI 1.52-574.57) or ILD (p = 0.0037, Pc = 0.0148, OR 22.95, 95%CI 1.27-416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed. MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib.

We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme. Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs/LSCs and incidence rates (patients with events/100 patient-years) of SIEs and HZ were analysed over 75 months. Median ALCs were generally stable over 75 months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36-75. SIE/HZ incidence rates were higher in patients with ALC <0.5 × 103 cells/mm3 versus those with ALC ≥0.5 × 103 cells/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with/without SIEs or HZ events. SIE/HZ risk was highest in patients with ALC <0.5 × 103 cells/mm3, supporting this threshold as clinically relevant for defining increased SIE/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn.

Disease-modifying antirheumatic drug selection in Japanese patients with rheumatoid arthritis treated with biologics or JAK inhibitors without methotrexate: A retrospective hospital-based administrative claims database study.

We evaluated the medication selection and clinical characteristics of rheumatoid arthritis patients who started treatment with/without methotrexate (MTX) (using biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors instead) in Japan. Using a Japanese hospital-based administrative claims database, rheumatoid arthritis patients who received treatment [abatacept (ABA), interleukin-6 receptor inhibitor, tumor necrosis factor inhibitor, or Janus kinase inhibitor] between 1 January 2015 and 31 December 2019 were enrolled. Overall, 19,301 patients were included (10,530 receiving MTX; 8771 not receiving MTX within 60 days of the first treatment). Mean ages at diagnosis were 60.7 and 65.9 years in the MTX and non-MTX groups, respectively (P < .0001). The non-MTX group had higher proportions of patients with Charlson Comorbidity Index ≥1 (P < .0001) and higher comorbidity rates. ABA was the most frequently used drug among patients with infectious/parasitic, circulatory, and respiratory diseases at baseline. Interleukin-6 receptor inhibitor had the highest use rate among patients with neoplasms; blood, gastrointestinal, and genitourinary diseases; and abnormal clinical/laboratory findings. ABA had the highest persistence probability from 6 months onward. MTX is used less frequently among older Japanese rheumatoid arthritis patients or those with comorbidities. In such patients, ABA is the most frequently used drug, followed by interleukin-6 receptor inhibitor, when MTX is not used at treatment start.

Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35-3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients.

The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients. HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m2]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m2]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients. There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09-2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24-2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics. The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear.

Associations of HLA Polymorphisms with Anti-SARS-CoV-2 Spike and Neutralizing Antibody Titers in Japanese Rheumatoid Arthritis Patients Vaccinated with BNT162b2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019. Anti-SARS-CoV-2 spike (S) and neutralizing antibodies (Abs) are measured to evaluate the efficacy of vaccines. Human leukocyte antigen (HLA) may be associated with vaccine efficacy. Here, we investigated the association of HLA polymorphisms with the production of anti-SARS-CoV-2 S or neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Genotyping of DRB1 and DQB1 was conducted in 87 Japanese RA patients vaccinated with BNT162b2. Associations of allele or haplotype carrier frequencies with anti-SARS-CoV-2 S or neutralizing Abs were examined. DRB1*12:01 was significantly positively associated with the production of S Ab (p = 0.0225, odds ratio [OR] 6.08, 95% confidence interval [CI] 1.32-28.03). The DQB1*03:01 allele carrier frequency tended to be higher in high responders of S Ab. Allele carrier frequencies of DRB1*15:01 (p = 0.0102, OR 9.26, 95% CI 1.65-52.01) and DQB1*06:02 (p = 0.0373, OR 7.00, 95% CI 1.18-41.36) were higher in responders of neutralizing Ab. Haplotype and two-locus analyses of DRB1 and DQB1 suggested that DRB1 alleles were the primary drivers of these associations. Logistic regression analysis showed associations of these alleles independent of clinical characteristics. Independent associations were found between HLA alleles and anti-SARS-CoV-2 Ab production by vaccinated RA patients.

Association of a FAM13A variant with interstitial lung disease in Japanese rheumatoid arthritis

BackgroundInterstitial lung disease (ILD) occasionally occurs in rheumatoid arthritis (RA) and confers a dismal prognosis. We previously reported that a single-nucleotide variant (SNV) of MUC5B was associated with ILD in...

Cost-consequence of abatacept as first-line therapy in Japanese rheumatoid arthritis patients using IORRA real-world data.

To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Lack of Association of rs12702634 in RPA3-UMAD1 With Interstitial Lung Diseases in Japanese Rheumatoid Arthritis Patients.

Background:Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association.Methods:Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease.Results:No association was detected for rs12702634 with ILD in RA (P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association (P = .0996, OR 1.52, 95% CI 0.92–2.49).Conclusions:The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.

Real-world safety and efficacy of CT-P13, an infliximab biosimilar, in Japanese rheumatoid arthritis patients naïve to or switched from biologics.

The aim of this post-marketing surveillance (PMS) study is to evaluate the real-world safety and efficacy of CT-P13, the first biosimilar of infliximab (IFX). Japanese patients with rheumatoid arthritis were prospectively registered from November 2014 and followed up for 1 year. Of 794 patients in the analysis set, 318 patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) showed an immediate decrease in Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and increased remission rate (DAS28-CRP < 2.6). In patients who switched from IFX to CT-P13 for non-medical reasons (n = 374), the low DAS28-CRP due to previous IFX treatment decreased further with continued CT-P13 therapy. As in naïve patients, patients who switched from other bDMARDs, mainly for medical reasons (n = 102), responded similarly to CT-P13. CT-P13 in this PMS and IFX in a previous PMS had similar adverse reaction profiles, although the incidence rate in naïve patients in this current PMS was lower due to earlier initiation of CT-P13 therapy. CT-P13 showed excellent effectiveness as first-line therapy, no clinical difficulties in switching from IFX, and clinical improvement in patients who failed other bDMARDs. CT-P13 could be a cost-effective alternative to IFX in the treatment of rheumatoid arthritis.

Risk of serious infection, malignancy, or death in Japanese rheumatoid arthritis patients treated with a combination of abatacept and tacrolimus: a retrospective cohort study

To evaluate whether combinatorial use of abatacept (ABT) and tacrolimus (Tac) increases the risk of adverse events compared to their individual use in Japanese rheumatoid arthritis (RA) patients. We conducted a retrospective cohort study of RA patients using the Japanese multicenter database and analyzed the data of RA patients registered from April 2010 to March 2019 by comparing three treatment groups who received Tac, ABT, or a combination of both. We included patients who had initiated treatment with ABT or Tac and excluded patients who used tumor necrosis factor inhibitors, IL-6 inhibitors, and Jak inhibitors in the first year of our study. The primary outcome was the occurrence of adverse events such as infections that required hospitalization, newly diagnosed malignancy, or death from any cause after initiation of ABT or Tac. Of the 27,032 RA patients in the registry, 2009 patients were included. The Tac, ABT, and combination groups consisted of 1328, 563, and 118 patients, respectively. Primary outcome occurred in 149 (13.4%), 62 (13.5%), and 14 (13.9%) patients of the Tac, ABT, and combination groups, respectively. The incidence of adverse events between groups was not significantly different (p = 0.638). A Cox regression analysis which was adjusted for potential confounders such as age, disease activity, and concomitant use of prednisolone revealed no significant differences between groups. The combinatorial use of ABT and Tac, or ABT alone does not increase the risk of adverse events when compared to the use of Tac alone in RA patients in Japan. Key Points • This study included Japanese rheumatoid arthritis data and found that there was no significant risk when patients were treated with a combination of Tac and ABT or each drug alone.

The Effectiveness and Retention Rate of Iguratimod in Japanese Rheumatoid Arthritis Patients with/without Methotrexate in Daily Medical Care.

(1) Background: We evaluated the clinical response of iguratimod (IGU) in patients with rheumatoid arthritis (RA) being treated with or without methotrexate (MTX) over 54 weeks. (2) Methods: 106 patients with RA undergoing IGU were retrospectively observed. RA patients were divided into those treated with MTX+IGU (n = 35) and those treated with IGU (n = 71). The primary endpoint was the clinical response of the Disease Activity Score assessing 28 joints with C-reactive protein (DAS28-CRP) differences in the changes from baseline to 54 weeks between MTX+IGU and IGU groups. Secondary endpoints, such as the clinical response, retention rate, and safety, were evaluated. (3) Results: The DAS28-CRP difference in the changes between the two groups were −0.2. DAS28-CRP were significantly reduced from the baseline in the MTX+IGU and IGU groups (−1.43 and −1.20 from baseline, respectively). The retention rates were 71.4% in the MTX+IGU groups and 59.2% in the IGU groups (p = 0.16). Adverse events were observed in a total of 6 (17.1%) MTX+IGU patients and 20 (28.2%) IGU patients (p = 0.21). (4) Conclusions: IGU therapy may be a useful treatment option for patients who cannot be treated with MTX.

Association of the RPA3-UMAD1 locus with interstitial lung diseases complicated with rheumatoid arthritis in Japanese

ObjectivesThe genetic background of rheumatoid arthritis–interstitial lung disease (RA-ILD) has been evaluated in Europeans, but little knowledge has been obtained in non-Europeans. This study aimed to elucidate genome-wide risk of...

Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab.

To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI]≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models. Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6-81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72-83.80) were independent predictors of disease flare. Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. jRCTs041180071, UMIN000021247.

Clinical Characteristics of Frailty in Japanese Rheumatoid Arthritis Patients

ObjectiveThe relationship between clinical characteristics and frailty was investigated in rheumatoid arthritis (RA) patients >40 years old.MethodsRA patients followed for >1 year were interviewed and diagnosed as frail according to a 5-item frailty score index: (1) weight loss >2 kg within 6 months (WL); (2) slower gait speed (GS); (3) exercise less than once per week (EX); (4) decline in short-term memory (SM); and (5) general fatigue in the past 2 weeks (GF). The relationship between frailty status and background parameters was evaluated.ResultsAmong 739 subjects, frail patients comprised 221, pre-frail patients comprised 203, and robust comprised 315. The most common symptom in the Frailty group was GS, followed by SM, GF, EX, and WL, whereas the most common symptom in the Pre-frailty group was GS followed by SM, GF, WL, and EX. Frailty was significantly correlated with aging. Elderly onset rheumatoid arthritis, disease activity, serum C-reactive protein concentration, degree of joint deformity, activities in daily living (ADL), dementia treated, and glucocorticoid steroid administration demonstrated significant correlations with frailty status, although all factors also demonstrated significant correlation with aging. In addition, the EuroQol score (EQ5D) was significantly correlated with both aging and frailty.ConclusionThe results suggest that a remission state for disease activity, ADL, and dementia is correlated with frailty. The most common and primary symptom is GS. Elderly RA patients require careful attention for symptoms of frailty, which may damage the EQ5D score, specifically, the quality of life for RA patients.

Correlation between frailty and disease activity in patients with rheumatoid arthritis: Data from the CHIKARA study.

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. 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. 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. 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.

Suppression of joint destruction with subcutaneous tocilizumab for Japanese patients with rheumatoid arthritis in clinical practice

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting.Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI).Results: At baseline, the patients’ mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were naïve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to −0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified.Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period.

Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab: An interventional study

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX.Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36.Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1–18.4%; p= .025).Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.

Shared Decision-Making and Patient Satisfaction in Japanese Rheumatoid Arthritis Patients: A New "Preference Fit" Framework for Treatment Assessment.

IntroductionWe have developed a new framework to assess shared decision-making (SDM) as a tool to improve patient satisfaction. This framework is based on a “preference fit” index that relates SDM to patient treatment preferences and patient satisfaction in a sample of rheumatoid arthritis (RA) patients in Japan.MethodsWe surveyed 500 RA patients in Japan and explored the interactions between the treatment preference fit index, SDM, and overall patient satisfaction.ResultsOur new preference fit index reveals significant impact on patient satisfaction: the better the fit between SDM and patient preferences, the higher the patient satisfaction with the current treatment. Patients treated with biologic agents were more satisfied. Patients suffering from depression or migraines scored significantly lower both on our preference fit measure and for overall patient satisfaction.ConclusionThe association between depression and a low treatment preference fit suggests that depression may pose challenges to SDM and that doctors in Japan are less attuned to the SDM preferences of depressed patients.FundingJanssen Pharmaceutical KK.