Chinese Rheumatoid Arthritis Patients Research Articles

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World.

PurposeTo compare the efficacy, safety, and cost-effectiveness of methotrexate (MTX) plus hydroxychloroquine (HCQ) vs MTX plus leflunomide (LEF) in established rheumatoid arthritis (RA) with inadequate response to MTX monotherapy in a real-world Chinese cohort.Patients and MethodsA prospective RA cohort (n=549) was screened with eligible patients who had inadequate response (disease activity score in 28 joints using erythrocyte sedimentation rate, DAS28-ESR>3.2) to initial MTX monotherapy and subsequently received either MTX+HCQ or MTX+LEF. Propensity score matching (PSM) was applied to adjust the possible baseline confounders between two groups. The primary outcome was the proportion of patients achieving first remission (DAS28-ESR<2.6) during follow-up by log rank test. Secondary outcomes were changes of DAS28, glucocorticoids (GCs) exposure, safety, cost-effectiveness, sustained remission, and low disease activity (LDA) rate after 24-month follow-up.ResultsOverall, 222 eligible patients were subjected to the aforementioned two treatment protocols (MTX+HCQ, n=102; MTX+LEF, n=120). After PSM adjustment, 97 patients in each group were analyzed. A higher remission rate was observed in the MTX+HCQ group than in the MTX+LEF group (70.1% vs 56.7%, P=0.048). The median time to remission was 11 and 16 months in the two groups, respectively. At the endpoint, more patients achieved remission (46.8% vs 32.5%, P=0.063) and maintained sustained LDA in the HCQ group (53.2% vs 38.6%, P=0.062) and also more patients withdrew GCs in this group (32% vs 16.7%, P=0.053) than those in the LEF group. Safety profiles were non-alarming, with no significant difference between the two groups. The incremental cost-effectiveness ratio yielded by MTX+HCQ over MTX+LEF was $1,111.8 per quality-adjusted life-year (QALY), within the cost-effective threshold set as the per capita gross domestic product (GDP) of China.ConclusionThe MTX+HCQ combination was seemingly superior to MTX+LEF in a real-world cohort of Chinese RA patients with inadequate response to methotrexate monotherapy in respect of the efficacy and cost-effectiveness.

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

IntroductionBaricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.MethodsIn this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician’s Global Assessment of Disease Activity, Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.ResultsStatistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.ConclusionsThe efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.Trial RegistrationNCT02265705Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00231-6) contains supplementary material, which is available to authorized users.

Serum levels of 14-3-3η are associated with increased disease risk, activity and duration of rheumatoid arthritis in Chinese patients.

The aim of the present study was to determine the association between serum 14-3-3η expression levels and disease risk, inflammation level and disease duration in Chinese patients with rheumatoid arthritis (RA). A total of 45 Chinese patients with RA, 45 patients with osteoarthritis (OA) and 44 age- and sex-matched (with the RA group) healthy control (HC) subjects were consecutively recruited for the present case-controlled study. In addition, the demographic and clinicopathological characteristics of the patients with RA were collected. Serum samples were obtained from patients with RA, patients with OA and the HCs, and the serum levels of 14-3-3η were determined by ELISA. Compared with that in the OA patients (P=0.006) and HCs (P<0.001), 14-3-3η expression was significantly increased in RA patients, and receiver operating characteristics (ROC) analysis indicated that it served as a potential predictive marker for the risk of RA. In patients with RA, serum levels of 14-3-3η were positively correlated with disease duration (P=0.003), erythrocyte sedimentation rate (P=0.006) and disease activity score in 28 joints (P=0.025). The proportion of rheumatoid factor (RF)-positive patients (P=0.023) and anti-citrullinated protein antibody (ACPA)-positive patients (P=0.002) with RA was increased (when 14-3-3η expression was increased) compared with RF-negative patients or ACPA-negative patients, respectively. Of note, 14-3-3η serum levels were able to distinguish patients with established RA (disease duration, >2 years) from patients with early RA (disease duration, ≤2 years) with an AUC of 0.759 (95% CI, 0.612-0.905), and the sensitivity and the specificity at the best cut-off point (14-3-3η=0.613 ng/ml) were 79.3 and 75.0%, respectively. Furthermore, 14-3-3η was able to differentiate between RF-positive RA patients and RF-negative patients or HCs. In conclusion, circulating 14-3-3η expression may serve as a novel biomarker for disease risk and activity of RA in Chinese patients.

Cost-effectiveness analysis of etanercept plus methotrexate vs triple therapy in treating Chinese rheumatoid arthritis patients.

Objective:This study aimed to explore the cost-effectiveness of etanercept plus methotrexate (ETN+MTX) compared to triple disease-modifying anti-rheumatic drugs (DMARDs) in treating Chinese rheumatoid arthritis (RA) patients.Methods:The 134 Chinese RA patients who were about to initiate ETN+MTX or triple DMARDs therapy based on treat-to-target strategy were consecutively recruited and categorized into ETN+MTX group (N = 49) or triple DMARDs group (N = 85). Treatment efficacy was assessed at month 3 (M3)/M6/M9/M12 after initiation of treatment. Also, 1-year treatment cost was evaluated, and cost-effectiveness analysis and sensitivity analysis were conducted.Results:RA patients in ETN+MTX group exhibited similar disease activity and quality of life at each time point while elevated 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) change (M0-M12) and low disease activity rate compared with triple DMARDs group. For 1-year treatment cost, ETN+MTX required increased drug cost, decreased other medical cost, and finally elevated total cost compared with triple DMARDs. Meanwhile, compared to triple DMARDs, ETN+MTX produced an additional quality-adjusted life year (QALY) of 0.015, resulting in an incremental cost-effectiveness ratio (ICER) of ¥2,939,506.7 per QALY that was 53.1 folds of gross domestic product (GDP) per capita in China. More interestingly, sensitivity analysis revealed that the ETN price had to be reduced at least by 71.3% before ETN+MTX became cost-effectiveness compared to triple DMARDs.Conclusion:ETN+MTX is less cost-effective in treating Chinese RA patients compared with triple DMARDs.

Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis.

Aims:We performed an updated meta-analysis to verify correlations between gene polymorphisms and adverse events in methotrexate (MTX)-treated rheumatoid arthritis (RA) patients. Then, we conducted a retrospective cohort study of Han Chinese in China.Methods:Relevant studies were collected from the PubMed database and the EMBASE database until December 2017. Pre-allele, dominant, recessive, codominant, and homozygotic models were applied. In addition, a retrospective cohort study enrolling 162 RA patients treated with MTX was conducted. Single nucleotide polymorphism (SNP) genotyping was analyzed by PCR and product sequencing.Results:A total of 39 studies were included in 20 meta-analyses; meta-analysis showed a significant association between MTX-related toxicity and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T(rs1801133) polymorphism in East Asian RA patients, and significant associations were observed between MTX-related toxicity and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) 347C>G (rs2372536), reduced folate carrier 1 (RFC-1) 80G>A (rs1051266), and adenosine triphosphate-binding cassette B1 (ABCB1) 3435C>T(rs1045642) polymorphisms in European RA patients but not in East Asian RA patients. Moreover, in our retrospective cohort study, ATIC 347C>G(rs2372536) and ABCB1 3435C>T(rs1045642) polymorphisms were not associated with MTX-related toxicity. However, a significant association was observed between MTX-related toxicity and RFC-1 80G>A (rs1051266) polymorphism in Chinese Han RA patients.Conclusion:Evidence-based results suggest that the MTHFR 677C>T(rs1801133), ATIC 347C>G(rs2372536), RFC-1 80G>A (rs1051266), ABCB1 3435C>T(rs1045642) polymorphisms are associated with MTX-related toxicity. Larger and more stringent study designs may provide more accurate findings for the effects of these SNPs on MTX-related toxicity, and larger sample-size studies of the Chinese Han population should be conducted for further validation.

Periodontal disease in Chinese patients with rheumatoid arthritis: A case-control study.

To evaluate the prevalence and severity of periodontal disease in Chinese rheumatoid arthritis patients. This cross-sectional study included 128 RA and 109 healthy controls. Two dentists conducted periodontal status including Plaque index (PI), Gingival index (GI), pocket probing depths (PPDs), Clinical attachment level (CAL) and Bleeding on probing (BOP) independently. Sociodemographic, lifestyle, clinical parameters and use of medication were assessed. Data were analyzed by Student's t test, χ2 test, Wilcoxin-Mann- Whitney's test, Correlational Analysis, univariate or multivariate logistic regression. The periodontal status was significantly worse in RA, especially the condition of dental and gingival status. RA had 4.68-fold. After adjusted potential risk factors, RA had 10.26-fold. The independent variable related to GI was DAS28 (p=.05) negatively, to the contrary, ESR (p=.013) was positively associated; the independent variable positively and related to periodontitis was educational level (p=.021) and anti-CCP positivity (p=.002). Through multivariate logistic regression, age and swollen joint were the independent variable related to periodontitis of RA (OR 1.087, p=.044) and (OR 1.560, p=.008) respectively. Chinese RA patients show higher odds of PD. It is important to take early interventions in combination with medical therapy.

Membrane-Spanning Protein Genetic Polymorphisms Related to Methotrexate Therapeutic Outcomes in a Chinese Rheumatoid Arthritis Population.

Methotrexate (MTX) is a first-line disease-modifying antirheumatic drug for rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. The differences in drug efficacy and adverse drug reactions may be caused by genetic variations. We investigated the effects of single-nucleotide polymorphisms (SNPs) in 2 genes encoding membrane-spanning proteins, namely, reduced folate carrier-1 RFC-1/SLC19A1 (G>A [rs7499], A>G [rs2838956] and 180G>A [rs1051266]) and adenosine triphosphate-binding cassette B1 (rs1045642). Tagged SNPs were genotyped in 162 patients with RA in China. Then, we analyzed the relationships between these SNPs and therapeutic outcomes related to MTX in Chinese RA patients. No significant associations were found between the RFC-1/SLC19A1 (G>A [rs7499] and A>G [rs2838956]) and adenosine triphosphate-binding cassette B1 (rs1045642) gene polymorphisms and the response to MTX in RA patients. However, MTX-related toxicity was associated with one SNP, RFC-1 rs1051266 AA vs GG (odds ratio, 6.523; 95% confidence interval, 1.596-26.565; P = .009). SLC19A1 A>G rs2838956 showed a trend toward a significant association (odds ratio, 0.377; 95% confidence interval, 0.124-1.143; P = .085) with toxicity. Our results suggest that the RFC-1 80G>A (rs1051266) SNP exerts a potentially protective effect against the risk of adverse drug reactions in Chinese RA patients treated with MTX. Further studies are required to validate these findings.

Effects of vitamin D on disease activity and serum interleukin-6 in rheumatoid arthritis.

Vitamin D3 or 25(OH)D3 may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6). The aim of this study is to determine the clinical factors of vitamin D deficiency in multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 levels. One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D3 and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading doses of vitamin D3 and repeated assessments were done. Vitamin D deficiency (<50nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D3 levels compared to Malays and Indians (P<0.001). Serum 25(OH)D3 level was still negatively associated with body mass index in RA patients (P=0.002) after adjustment for potential confounding variables. No significant association was seen between 25(OH)D3 levels and disease activity or serum IL-6 levels in both pre- and post-treatment groups. A negative association was observed between serum 25(OH)D3 and functional disability, including a 33% improvement post-treatment (mean±SD: 0.30±0.46 to 0.20±0.18). Vitamin D deficiency is prevalent in Malaysian RA patients. This study suggests that vitamin D is not associated with disease activity or serum IL-6 levels but it may have a role in functional disability in RA patients.

Myopenia is associated with joint damage in rheumatoid arthritis: a cross-sectional study.

BackgroundThe link between body mass index (BMI) and disease characteristics in rheumatoid arthritis (RA) remains controversial. Body composition (BC) has been more frequently recommended to be used instead of BMI for more accurate assessment. Our study aimed to investigate the characteristics of BC in RA patients and their associations with disease characteristics.MethodsBody composition was assessed in consecutive Chinese RA patients and control subjects by bioelectric impedance analysis. Overfat was defined by body fat percentage (BF%) as ≥25% for men and ≥35% for women. Myopenia was defined by appendicular skeletal muscle mass index (ASMI) ≤7.0 kg/m2 in men and ≤5.7 kg/m2 in women. BMI and clinical data including disease activity, function, and radiographic assessment were collected. Active disease was defined by disease activity score in 28 joints with four variables including C‐reactive protein (DAS28‐CRP) ≥2.6. Functional limitation was defined as Stanford health assessment questionnaire disability index (HAQ‐DI) >1. Radiographic joint damage (RJD) was defined as the Sharp/van der Heijde modified sharp score (mTSS) >10.ResultsThere were 457 RA patients (mean age 49.5 ± 13.1 years old with 82.7% women) and 1860 control subjects (mean age 34.3 ± 9.9 years old with 51.2% women) recruited. Comparisons of BMI and BC between RA patients and control subjects in age and gender stratification showed that lower BMI with 17.7% underweight and lower ASMI with 45.1% myopenia are the main characteristics in RA patients. Compared with those without myopenia, RA patients with myopenia had significantly higher DAS28‐CRP (median 3.5 vs. 3.0), higher HAQ‐DI (median 0.38 vs. 0.13) with higher rate of functional limitation (24.8% vs. 7.6%), and higher mTSS (median 22.3 vs. 9.0) with more RJD (71.8% vs. 45.8%) (all P < 0.001). Multivariate logistic regression analysis showed myopenia were positively associated with functional limitation (OR = 2.546, 95% CI: 1.043–6.217) and RJD (OR = 2.660, 95% CI: 1.443–4.904). All RA patients were divided into four BC subgroups according to overfat and myopenia. Those with both overfat and myopenia had the worst disease characteristics. After adjustment for confounding factors, significant additive interactions were observed between overfat and myopenia in active disease (AP = 0.528, 95% CI: 0.086–0.971), functional limitation (AP = 0.647, 95% CI: 0.356–0.937), and RJD (AP = 0.514, 95% CI: 0.139–0.890).ConclusionsMyopenia is very common in RA patients that is associated with functional limitation and joint damage in RA. Further research on the underlying mechanism and the effect of skeletal muscle mass improvement in RA management are worth exploring in the future.

Increased Risk of Thyroid Dysfunction Among Patients With Rheumatoid Arthritis.

Background: Thyroid dysfunction seems to be common among rheumatoid arthritis (RA) patients, but the risk of thyroid dysfunction in RA has not been well-defined.Methods: We performed a case-control study of 65 RA patients and 550 matched non-RA subjects to assess the risk of thyroid dysfunction among Chinese RA patients. A systematic review and meta-analysis was also conducted to comprehensively define the relationship between RA and thyroid dysfunction.Results: The case-control study indicated that the prevalence of thyroid dysfunction was significantly higher in RA patients than controls (OR = 2.89, P < 0.001). Further subgroup analyses revealed positive correlations of RA with hypothyroidism (OR = 2.28, P = 0.006) and hyperthyroidism (OR = 8.95, P < 0.001). Multivariate logistic regression analysis revealed an independent association between RA and thyroid dysfunction (Adjusted OR = 2.89, 95%CI 1.63–5.12, P < 0.001). Meta-analysis of 15 independent studies also showed an obviously increased risk of thyroid dysfunction among RA patients (RR = 2.86, 95%CI 1.78–4.58, P < 0.001). Further subgroup analysis showed RA could obviously increase risk of hyperthyroidism (RR = 2.73, 95%CI 1.29–5.77, P = 0.043) and hypothyroidism (RR = 2.02, 95%CI 1.49–2.74, P < 0.001).Conclusion: Our study provides strong evidence for the increased risk of thyroid dysfunction among RA patients. Screening of thyroid dysfunction may be recommended for RA patients.

Associations of TRAF1/C5 rs10818488 and rs3761847 polymorphisms with genetic susceptibility to rheumatoid arthritis: a case-control study and updated meta-analysis.

The results on associations of tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) rs10818488 and rs3761847 polymorphisms with rheumatoid arthritis (RA) are controversial, thus this study was performed to examine whether the aforementioned polymorphisms were associated with RA in a Chinese population. Furthermore, an updated meta-analysis was conducted. The polymorphisms were genotyped in 328 Chinese RA patients and 449 healthy controls. Studies examining the association of TRAF1/C5 rs10818488 and/or rs3761847 polymorphism with RA were exhaustively searched. No significant difference in either genotype or allele distribution between RA patients and controls was found. The updated meta-analysis was conducted based on 19 articles including the present study. A significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele in Europeans (OR = 0.843, 95% CI = 0.730-0.975, p = 0.021) and in Asians (OR = 1.070, 95% CI = 1.009-1.136, p = 0.024) was found. Additionally, a significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele under the recessive model in Asians (OR = 1.129, 95% CI = 1.023-1.246, p = 0.016) and in Africans (OR = 0.657, 95% CI = 0.507-0.851, p = 0.001) was found. Only a borderline significant association of RA with TRAF1/C5 rs3761847 polymorphism A allele was found in Europeans. Non-significant associations of RA with TRAF1/C5 rs10818488 and rs3761847 polymorphisms were found in our study. The updated meta-analysis results demonstrate that TRAF1/C5 rs10818488 polymorphism is associated with RA in Europeans, Asians and Africans, and TRAF1/C5 rs3761847 polymorphism is associated with RA in Europeans with borderline significant evidence.

Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population.

Objective: Analysis of the relationship between single nucleotide polymorphisms (SNPs) and outcomes of methotrexate (MTX) therapy for rheumatoid arthritis (RA) in China.Materials and Methods: TYMS 28 bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) enzyme proteins may be related to the outcomes of MTX therapy, according to our previous meta-analysis. A total of 162 patients with RA were included in our study. SNPs were evaluated using polymerase chain reaction (PCR). Disease Activity Score 28 (DAS28) was used to evaluate the clinical response, and adverse drug reactions (ADRs) were collected after physical examinations of the patients.Results: The MTHFR 677C>T gene showed a relationship with the ADRs of MTX in the Recessive model [TT vs. (CC+CT)] (p = 0.04, OR = 2.20, 95% CI: 1.01, 4.77). In the Codominant model [CT vs. (CC+TT)], the MTHFR 677C>T gene also showed a trend of association with ADRs (p = 0.08, OR = 0.52, 95% CI: 0.25, 1.08). No significant difference was found between TYMS, MTHFR, ATIC, MTR, and MTRR gene polymorphisms and the RA response or ADRs related to MTX in our study.Conclusion: Our results showed that the MTHFR [677C>T (rs1801133)] TT genotype is associated with ADRs to MTX in Chinese RA patients. Other SNPs, including TYMS 28bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) gene polymorphisms, were not associated with MTX treatment outcomes. Further studies are required to validate these findings.

Motion analysis of the wrist joints in Chinese rheumatoid arthritis patients: a cross-sectional study

BackgroundThe wrist is often severely affected in rheumatoid arthritis (RA) patients; however, little is known about the potential risk factors of the reduced wrist range of motion. In this study, we explored a broad range of possible risk factors of wrist range of motion in RA patients. We also determined whether measurements of wrist range of motion reflect Sharp score for the wrists.MethodsActive wrist volar flexion, dorsal flexion, radial deviation and ulnar deviation were assessed using a goniometer. RA patients underwent standardized laboratory and radiographic examinations and completed several questionnaires. A linear regression model was used to study association between the wrist range of motion and independent variables. In addition, Spearman and Pearson correlation analysis were used to compare influence factors and outcome measurements between the measurements of wrist range of motion and Sharp score for the wrists.ResultsIn this study, lower socioeconomic status, longer disease duration, severe pain, higher disease activity and drug treatments were associated with reduced wrist range of motion in RA patients (n = 102, 86.3% female, mean ± SD age, 55.0 ± 11.7 years, and mean ± SD disease duration, 8.4 ± 8.7 years). Furthermore, wrist range of motion was highly correlated with Sharp score for the wrists (P < 0.05).ConclusionsSocioeconomic status and disease-specific factors were significantly associated with wrist range of motion in RA patients. The results indicated that rheumatologists and nurses should note the measurements of wrist range of motion in RA patients, especially those with a low socioeconomic status, a long disease duration, severe pain, and high disease activity to develop strategies to improve their quality of life.

Intervention of integrative medicine treatment has impact on serum levels of ET-1, TNF-α, MLT in RA-CVD.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can destroy peripheral joints. However, very little is known regarding specific biological marker for RA in Chinese patients. In this study, we determined the serum biomarkers and clinical features of RA-CVD. We also evaluated the short-term efficacy of routine RA treatment combined with integrative medicine treatment on RA-CVD. We found that anti-cyclic citrullinated peptide (CCP) and disease activity score in 28 joints (DAS28) are associated with risks of cardiovascular disease (CVD) in RA. And, melatonin (MLT) may play a negative regulatory role in cardiovascular damage in patients with RA. Furthermore, endothelin (ET-1) and inflammatory markers may be subclinical cardiovascular damages in RA. Moreover, of the 17 patients with RA-CVD, test results of ET-1, TNF-α and OSCAR after integrative medicine treatment were significantly decreased than before treatment. Collectively, our results provide a therapeutic potential of integrative medicine to the treatment of RA-CVD.

Joint damage is amplified in rheumatoid arthritis patients with positive thyroid autoantibodies.

BackgroundAutoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse. Here, we aimed to evaluate the incidence of TAbs in a consecutive Chinese RA cohort and to investigate whether the elevated presence of TAbs is associated with joint damage and synovitis in RA patients.MethodsA total of 125 hospitalized RA patients were consecutively recruited. Clinical data and available synovial tissues were collected at baseline, and TAbs and thyroid function were detected by chemiluminescent immunoassay. Patients who tested positive for TPOAbs or TgAbs were classified as the TAbs-positive group, and patients who tested positive for neither TPOAbs nor TgAbs were recruited as the TAbs-negative group. Disease activity was assessed using DAS28-ESR (the disease activity score in 28 joints and including the erythrocyte sedimentation rate). X-ray assessment of the hand/wrist was performed according to the Sharp/van der Heijde-modified Sharp score (mTSS), and patients with an mTSS score >10 were defined as having radiographic joint damage (RJD). Serial tissue sections were stained immunohistochemically for CD3, CD15, CD20, CD34, CD38, and CD68, and synovitis were assessed according to Krenn’s synovitis score.ResultsA total of 44 (35%) patients were positive for either TPOAbs or TgAbs. Importantly, there was a significantly greater percentage of patients with RJD in the TAbs-positive group versus the TAbs-negative group (68% vs. 42%, p = 0.005). Compared with the TAbs-negative group, significantly more CD38-positive plasma cells infiltrated the TAbs-positive synovium, and a higher percentage of patients with high-grade synovitis were observed in the TAbs-positive group (5/8, 63% vs. 5/14, 36%). Moreover, RF positivity and disease activity indicators, including TJC28, DAS28-ESR, and CDAI, were significantly higher in the TAbs-positive group (all p < 0.05). Adjusted logistic regression analysis revealed that positive TAbs (OR 2.999, 95% CI [1.301–6.913]; p = 0.010) and disease duration (OR 1.013, 95% CI [1.006–1.019]; p < 0.001) were independently associated with RJD, and an odds ratio of 2.845 (95% CI [1.062–7.622]) was found for RJD in women with positive TAbs (n = 37) compared with those without TAbs (n = 59) (p = 0.038).ConclusionOur data showed that joint destruction was amplified in RA patients with an elevated presence of TAbs, which supports the importance and necessity of TAbs and thyroid function screening and monitoring in RA patient management in clinical practice.

Prediction of future rheumatoid arthritis in Chinese patients with early arthritis: An effective way of patient care

Objective: This was the first study to investigate the role of inflammatory biomarkers as predictors of future RA in Chinese patients with early onset of arthritis symptoms. The primary objective of this study was to check the involvement of inflammatory biomarkers as predictors of future RA in Chinese patients with early onset of arthritis symptoms. Methods: Adult patients of either gender (aged between 20 to 65 years) who had mild sign and symptoms of arthritis (morning stiffness, mild swollen joint, mild pain in joints) were enrolled. The sign and symptoms of arthritis were measured in each enrolled patient. All the patients were followed up for 6-month intervals till clinical diagnosis of RA confirmed (max 3 year). Laboratory investigation was performed at every follow up visit. Results: A total of 112 patients agreed to participate in our study, and willing to provide data as required by study, and completed the study. We found that the patients who had increased levels of rheumatoid factor of different immunoglobulin had high chance of developing RA. Similar trend was observed for antiperinuclear factor (APF) and antikeratin antibodies. The level of antinuclear antibodies was more among subjects who were diagnosed with RA than the subjects who don't have RA. Conclusion: Our study results suggested that the inflammatory biomarkers can be considered as predictors of future RA in Chinese patients with early onset of arthritis symptoms. Our study results support the hypothesis that biomarkers can be considered as one of the key predictors of future RA in Chinese patients with early onset of arthritis symptoms.

Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing.

Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease. However, genetic and environmental factors involved in RA pathogenesis are still remained largely unknown. To identify the genetic causal variants underlying pathogenesis and disease progression of RA patients, we undertook the first comprehensive whole-exome sequencing (WES) study in a total of 124 subjects including 58 RA cases and 66 healthy controls in Han Chinese population. We identified 378 novel genes that were enriched with deleterious variants in RA patients using a gene burden test. The further functional effects of associated genetic genes were classified and assessed, including 21 newly identified genes that were involved in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, focal adhesion and glycerophospholipid metabolism pathways relevant to RA pathogenesis. Moreover, six pathogenic variants were investigated and structural analysis predicted their potentially functional alteration by homology modeling. Importantly, five novel and rare homozygous variants (NCR3LG1, RAP1GAP, CHCHD5, HIPK2 and DIAPH2) were identified, which may exhibit more functional impact on RA pathogenesis. Notably, 7 genes involved in the olfactory transduction pathway were enriched and associated with RA disease progression. Therefore, we performed an efficient and powerful technique WES in Chinese RA patients and identified novel, rare and common disease causing genes that alter innate immunity pathways and contribute to the risk of RA. Findings in this study may provide potential diagnostic tools and therapeutic strategies for RA patients.

Chinese Registry of rheumatoid arthritis (CREDIT): II.\xa0prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis

BackgroundRheumatoid arthritis patients are at higher risk of developing comorbidities. The main objective of this study was to evaluate the prevalence of major comorbidities in Chinese rheumatoid arthritis patients. We also aimed to identify factors associated with these comorbidities.MethodsBaseline demographic, clinical characteristics and comorbidity data from RA patients enrolled in the Chinese Registry of rhEumatoiD arthrITis (CREDIT) from Nov 2016 to August 2017 were presented and compared with those from five other registries across the world. Possible factors related to three major comorbidities (cardiovascular disease, fragility fracture and malignancy) were identified using multivariate logistic regression analyses.ResultsA total of 13,210 RA patients were included (80.6% female, mean age 52.9 years and median RA duration 4.0 years). Baseline prevalence rates of major comorbidities were calculated: CVD, 2.2% (95% CI 2.0–2.5%); fragility fracture, 1.7% (95% CI 1.5–1.9%); malignancy, 0.6% (95% CI 0.5–0.7%); overall major comorbidities, 4.2% (95% CI 3.9–4.6%). Advanced age was associated with all comorbidities. Male gender and disease duration were positively related to CVD. Female sex and longer disease duration were potential risk factors for fragility fractures. Ever use of methotrexate (MTX) was negatively related to baseline comorbidities.ConclusionsPatients with rheumatoid arthritis in China have similar prevalence of comorbidities with other Asian countries. Advanced age and long disease duration are possible risk factors for comorbidities. On the contrary, MTX may protect RA patients from several major comorbidities, supporting its central role in the management of rheumatoid arthritis.

Moderating role of self-efficacy on the associations of social support with depressive and anxiety symptoms in Chinese patients with rheumatoid arthritis.

PurposeRheumatoid arthritis (RA) is significantly associated with depression and anxiety. Social support and self-efficacy are the coping resources of psychological distress. However, little research is available on the interaction of social support and self-efficacy in RA patients. This study aimed to identify the prevalence of depressive and anxiety symptoms and to examine whether or not self-efficacy moderates the associations of social support with depressive and anxiety symptoms in Chinese RA patients.MethodsA multicenter, cross-sectional study was conducted in northeast of China from December 2014 to January 2016. A total of 297 RA patients completed the Center for Epidemiologic Studies Depression Scale, Zung Self-Rating Anxiety Scale, Multidimensional Scale of Perceived Social Support and General Self-Efficacy Scale. The associations of social support, self-efficacy and social support × self-efficacy interaction with depressive and anxiety symptoms were examined by hierarchical regression analysis. If the interaction was statistically significant, simple slope analysis was conducted.ResultsThe prevalence of depressive symptoms was 58.2%, while 47.5% RA patients had anxiety symptoms. Social support and social support × self-efficacy interaction were significantly associated with depressive symptoms. Social support, self-efficacy and their interaction were significantly associated with anxiety symptoms. The association between social support and depressive symptoms was gradually reduced in the low (1 standard deviation [SD] below the mean, B=−0.614, β=−0.876, P<0.001), mean (B=−0.395, β=−0.563, P<0.001) and high (1 SD above the mean, B=−0.176, β=−0.251, P=0.002) groups of self-efficacy. For anxiety symptoms, the association was also gradually reduced in the low (B=−0.527, β=−0.774, P<0.001), mean (B=−0.288, β=−423, P<0.001) and high (B=−0.049, β=−0.071, P=0.447) groups of self-efficacy.ConclusionThere was a high prevalence of depressive and anxiety symptoms in Chinese RA patients. Self-efficacy could attenuate the associations of social support with depressive and anxiety symptoms. Adequate social support and self-efficacy intervention should be provided to alleviate psychological distress.

Rheumatoid arthritis is associated with rs17337023 polymorphism and increased serum level of the EGFR protein

ObjectiveWe have previously described the association of rheumatoid arthritis (RA) prevalence and two epidermal growth factor receptor (EGFR) SNPs (rs17337023 and rs2227983) among the Taiwanese population. This present study aimed to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA.MethodsThe cohort study included 366 Taiwan’s Han Chinese RA patients and 326 age and gender matched healthy controls. Blood samples collected from the participants were analyzed to determine their serum EGFR levels and to identify EGFR SNPs from their genomic DNA. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. The relationship between EGFR SNP and the clinical manifestations of RA was evaluated.ResultsOur results showed that a statistically significant difference in genotype frequency distributions at rs17337023 SNP for RA patients and controls (p ˂ 0.05). In addition, compared with the haplotype frequencies between case and control groups, the RA patient with the GT haplotype appeared to be a significant “protective” haplotype compared with other haplotypes (OR: 0.73, 95% CI: 0.59–0.91; p = 0.005). Furthermore, the increased serum level of EGFR was also observed in RA patients (p ˂ 0.001).ConclusionOur study showed that RA is associated with rs17337023 SNP in EGFR gene and increased serum level of the EGFR protein. These findings suggest EGFR is worthy of further investigation as a therapeutic target for RA.