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.

Antibodies against Serum Anti-Melanoma Differentiation-Associated Gene 5 in Rheumatoid Arthritis Patients with Chronic Lung Diseases.

Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530-0.627 and 0.579, 95%CI 0.530-0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648-0.740, p = 5.08 × 10-5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed.

Trends in Treatment, Outcomes, and Incidence of Orthopedic Surgery in Patients with Rheumatoid Arthritis: An Observational Cohort Study Using the Japanese National Database of Rheumatic Diseases.

OBJECTIVE: In this study, we investigated the changes in clinical outcome, treatment, and incidence of orthopedic surgery in patients with rheumatoid arthritis (RA) from 2004 to 2014. METHODS: Data were studied from the Japanese nationwide cohort database, NinJa (National Database of Rheumatic Diseases by iR-net in Japan), from 2004 to 2014. The time trends in the incidence of orthopedic procedures were analyzed using linear regression analysis. The cross-sectional annual data were compared between 2004 and 2014 to analyze the changes in clinical outcome and treatment. RESULTS: The incidence of orthopedic surgeries in patients with RA consistently decreased from 72.2 procedures per 1000 patients in 2004 to 51.5 procedures per 1000 patients in 2014 (regression coefficient = -0.0028, 95% CI -0.0038 to -0.0019, p < 0.001). The greatest reduction was found in total knee arthroplasty and total hip arthroplasty. Disease activity and functional disability improved significantly over this decade. The proportions of patients receiving methotrexate and biologic disease-modifying antirheumatic drugs significantly increased from 39.6% and 1.7% in 2004 to 63.8% and 27.4% in 2014, respectively. CONCLUSION: The overall incidence of orthopedic surgeries in patients with RA significantly decreased, accompanied by improved clinical outcomes because of the expanded use of effective drugs; however, the declining trend differed between procedures or locations. The results from the present study suggest that there might be a change in supply and demand for orthopedic surgeries.

Early therapeutic intervention with methotrexate prevents the development of rheumatoid arthritis in patients with recent-onset undifferentiated arthritis: A prospective cohort study.

OBJECTIVES: To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers. METHODS: The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year. RESULTS: The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups. CONCLUSIONS: This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.

Prevalence of joint replacement surgery in rheumatoid arthritis patients: cross-sectional analysis in a large observational cohort in Japan.

The purpose of this study was to describe the prevalence of total joint arthroplasty (TJA) in Japanese rheumatoid arthritis (RA) patients undergoing conventional drug treatment in a large observational cohort in Japan. A total of 5,177 RA patients were studied for the prevalence of TJA, who were enrolled in the NinJa database during the fiscal year of 2006. The cases of 2,695 RA patients with more than ten years of disease duration were extracted and subjected to further analysis. The prevalence of TJA increased in accordance with the disease duration, and the prevalence was markedly increased after ten years. Among the 2,695 patients with more than ten years of disease duration, 1,431 TJAs were performed in 645 (24.6%) patients. The patients with TJA had higher disease activity than those without TJA. In this cross-sectional study, TJAs were performed in approximately a quarter of the Japanese RA patients with more than ten years of disease duration. The result showed that patients with higher disease activity required TJA.