HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

Association between nucleos(t)ide analogue therapy for hepatitis B and Sjögren's syndrome: 15-year analysis of the national database of Taiwan.

Hepatitis B virus (HBV) infection has been proposed to play a role in the development of Sjögren's syndrome. However, to date, there are no reports on the risk of SS in HBV-infected patients following nucleos(t)ide analogue therapy. Due to Taiwan has higher prevalence of HBV infection and therapy was well recorded in the Taiwan's single-payer national health insurance database, we hypothesized that a long-term retrospective analysis of the risk of Sjögren's syndrome in HBV-infected patients following nucleotide therapy will increase our understanding of Sjögren's syndrome development following HBV infection. We identified 26,147 adults diagnosed with HBV infection between 1997 and 2012 in claims data. Finally, a total of 3268 HBV-infected patients who ever received nucleotide therapy (treated cohort) were frequency-matched on age and sex at 1:4 ratios to select a control group of 13,072 counterparts without therapy (untreated cohort). To identify Sjögren's syndrome risk, competing risk analysis adjusted for all covariates was performed. The risk was significantly lower in the treated cohort (15-year cumulative incidence, 2.4%; 95% confidence interval [CI], 1.4%-3.7%) than in the untreated cohort (7.1%; 95% CI, 2.5%-15.2%) (p = .015), and the adjusted HR was 0.6 (95% CI, 0.41-0.88; p = .009). Multivariable stratified analysis further verified the consistent associations between nucleoside therapy and risk reduction of Sjögren's syndrome across all strata. Our finding suggests that HBV infection treated with nucleotides is associated with lower risk of Sjögren's syndrome, implying a potential role of HBV infection in the development of Sjögren's syndrome.

Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment.

BACKGROUND AND AIM: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis. METHOD: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded. RESULTS: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up. CONCLUSIONS: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.

The Essential Role of Peptidylarginine Deiminases 2 for Cytokines Secretion, Apoptosis, and Cell Adhesion in Macrophage.

OBJECTIVE: The study aims to investigate the functional roles of peptidylarginine deiminase 2 (PADI2) in macrophages. METHODS: The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) system was used to knockout PADI2 in U937 cells. U937 cells were introduced to differentiate macrophages and were stimulated with lipopolysaccharides (LPS). The protein expression of PADI2, PADI4, and citrullinated proteins were analyzed by Western blotting. The mRNA and protein levels of interleukin 1 beta (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using RT-PCR and ELISA, respectively. Cell apoptosis was analyzed using flow cytometry. Cell adhesion assay was performed using a commercially available fibrinogen-coated plate. RESULTS: PADI2 knockout could markedly suppress the PADI2 protein expression, but not the PADI4 protein expression. PADI2 knockout decreased the protein levels of citrullinated nuclear factor κB (NF-κB) p65, but not those of citrullinated histone 3, resulting in the decreased mRNA expression levels of IL-1ß and TNF-α in the U937 cells and IL-1ß and IL-6 in the differentiated macrophages and the macrophages stimulated with LPS. The cytokines levels of IL-1ß, IL-6, and TNF-α were all dramatically decreased in the PADI2 knockout group compared with in the controls. PADI2 knockout prevented macrophages apoptosis via the decreased caspase-3, caspase-2, and caspase-9 activation. PADI2 knockout also impaired macrophages adhesion capacity through the decreased protein levels of focal adhesion kinase (FAK), phospho-FAK, paxillin, phospho-paxillin, and p21-activated kinase 1. CONCLUSION: This study showed that PADI2 could promote IL-1ß, IL-6, and TNF-α production in macrophages, promote macrophage apoptosis through caspase-3, caspase-2, and caspase-9 activation and enhance cell adhesion via FAK, paxillin, and PAK1. Therefore, targeting PADI2 could be used as a novel strategy for controlling inflammation caused by macrophages.

Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

Low-dose 5-aza-2'-deoxycytidine pretreatment inhibits experimental autoimmune encephalomyelitis by induction of regulatory T cells.

Forkhead box P3 (Foxp3) is the major transcription factor controlling the development and function of regulatory T (Treg) cells. Previous studies have indicated epigenetic regulation of Foxp3 expression. Here, we investigated whether the deoxyribonucleic acid (DNA) methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) applied peripherally could modulate central nervous system (CNS) inflammation, by using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that disease activity was inhibited in a myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE mouse briefly pretreated with low-dose (0.15 mg/kg) 5-Aza, ameliorating significant CNS inflammatory responses, as indicated by greatly decreased proinflammatory cytokines. On the contrary, control EAE mice expressed high levels of IFN-γ and interleukin (IL)-17. In addition, 5-Aza treatment in vitro increased GFP expression in CD4(+)GFP(-) T cells isolated from GFP knock-in Foxp3 transgenic mice. Importantly, 5-Aza treatment increased Treg cell numbers, in EAE mice, at both disease onset and peak. However, Treg inhibition assays showed 5-Aza treatment did not enhance per-cell Treg inhibitory function, but did maintain a lower activation threshold for effector cells in EAE mice. In conclusion, 5-Aza treatment prevented EAE development and suppressed CNS inflammation, by increasing the number of Treg cells and inhibiting effector cells in the periphery.

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Context: Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). Objective: To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Methods: Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. Results: RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. Conclusion: This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

Sixteen prescribed Chinese herbal medicines provide time-dependent cardiorenal and survival benefits in patients with overall and advanced diabetic kidney disease: a real-world study in Taiwan.

Background: A causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved. Methods: This retrospective cohort study analyzed national health insurance claims data in 2000-2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers. Results: PRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61-0.70 vs. 0.81; 0.65-0.99), all-cause mortality (0.48; 0.47-0.49 vs. 0.59; 0.50-0.70), and cardiovascular mortality (0.50; 0.48-0.53 vs. 0.61; 0.45-0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24-0.38) vs. 0.61 years (0.13-1.10) for ESRD, 2.71 years (2.60-2.82) vs. 1.50 years (1.03-1.98) for all-cause mortality, and 1.18 years (1.09-1.28) vs. 0.59 years (0.22-0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD. Conclusion: This real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.

Anti-citrullinated protein antibodies activated ERK1/2 and JNK mitogen-activated protein kinases via binding to surface-expressed citrullinated GRP78 on mononuclear cells.

In a previous study, we found that anti-citrullinated protein antibodies (ACPAs) enhance nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α production by normal human peripheral blood mononuclear cells (PBMCs) and U937 cells via binding to surface-expressed citrullinated glucose-regulated protein 78 (cit-GRP78). However, the downstream signaling pathways remain unclear after binding. In the present study, we firstly measured the effects of different kinase inhibitors on ACPA-mediated TNF-α production from normal PBMCs and monocytes. Then, the native and phosphorylated mitogen-activated protein kinases (MAPKs) were detected in ACPA-activated U937 cells by Western blotting. We also explored the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in activating IκB kinase alpha (IKK-α) in ACPA-stimulated U937 cells. Finally, we measured the amount of cit-GRP78 from PBMC membrane extracts in RA patients and controls. We found that MAPK and Akt inhibitors, but not PI3K inhibitor, remarkably suppressed ACPA-mediated TNF-α production. Interestingly, ACPAs selectively activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 MAPK, in U937 cells. This activation was suppressed by cit-GRP78, but not GRP78. The JNK activation further enhanced the phosphorylation of Akt and IKK-α. The expression of cit-GRP78 on cell membrane was higher in RA than normal PBMCs. Taken together; these results suggest that through binding to surface, over-expressed cit-GRP78 on RA PBMCs, ACPAs selectively activate ERK1/2 and JNK signaling pathways to enhance IKK-α phosphorylation, which leads to the activation of NF-κB and the production of TNF-α .

Renal and survival benefits of seventeen prescribed Chinese herbal medicines against oxidative-inflammatory stress in systemic lupus erythematosus patients with chronic kidney disease: a real-world longitudinal study.

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000-2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia. Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE. Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25-0.79, p = 0.006), all-cause mortality (0.56; 0.43-0.75, p < 0.0001), non-cardiovascular mortality (0.56; 0.42-0.75, p < 0.0001), and hospitalization (0.72; 0.52-0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19-0.95, p = 0.004) for ESRD, 1.22 years (0.63-1.82, p < 0.0001) for all-cause mortality, and 1.21 years (0.62-1.80, p < 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan. Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition.

Association between Anti-Hepatitis C Viral Intervention Therapy and Risk of Sjögren's Syndrome: A National Retrospective Analysis.

Hepatitis C virus (HCV) infection is a potential risk factor for Sjögren's syndrome (SS). However, it is unclear whether anti-HCV intervention therapy could decrease SS risk. A retrospective cohort analysis from 1997-2012 comprising 17,166 eligible HCV-infected adults was conducted. By 1:2 propensity score matching, a total of 2123 treated patients and 4246 untreated patients were subjected to analysis. The incidence rates and risks of SS and death were evaluated through to the end of 2012. In a total follow-up of 36,906 person-years, 177 (2.8%) patients developed SS, and 522 (8.2%) died during the study period. The incidence rates of SS for the treated and untreated cohorts were 5.3 vs. 4.7/1000 person-years, and those of death for the treated and untreated cohorts were 10.0 vs. 14.8/1000 person-years. A lower risk of death (adjusted hazard ratio, 0.68; 95% CI, 0.53-0.87) was present in HCV-infected patients receiving anti-HCV therapy in multivariable Cox regression, and this remained consistent in multivariable stratified analysis. However, there were no relationships between anti-HCV therapy and its therapeutic duration, and SS risk in multivariable Cox regression. In conclusion, anti-HCV intervention therapy was not associated with lower SS risk in HCV-infected patients, but associated with lower death risk.

Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib.

OBJECTIVES: The aim of this study was to investigate hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving tofacitinib. METHOD: This was a retrospective study performed in a regional teaching hospital in southern Taiwan. During January 2017 and December 2020, patients with a clinician-confirmed diagnosis of RA using tofacitinib for at least 3 months were enrolled. Serum HBV DNA levels and serum alanine aminotransferase were followed up around every 3 to 6 months to assess HBV reactivation. RESULTS: A total of 98 patients with RA were enrolled, and eight were hepatitis B surface antigen positive (HBsAg+) (8.1%), 64 were HBsAg-negative (HBsAg-)/hepatitis B core antibody positive (HBcAb+) (65.3%). In the HBsAg+ patients, two patients received antiviral prophylaxis, and none of them had HBV reactivation or hepatitis flare-up. The HBV reactivation rate was 33.3% (2/6) in the HBsAg+ RA patient without antiviral prophylaxis. Among the HBsAg-/HBcAb+ patients, the HBV reactivation rate was 3.1% (2/64). The incidence rate of HBV reactivation was 153.8 per 1000 person-years for overall HBsAg+ patients and 250 per 1000 person-years after excluding patients receiving antiviral prophylaxis. The incidence rate was 11.2 per 1000 person-years for HBsAg-/HBcAb+ patients with RA receiving tofacitinib. CONCLUSION: Tofacitinib could induce HBV reactivation in both HBsAg+ and HBsAg-/HBcAb+ RA patients. HBsAg+ patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, closely monitoring HBV DNA and alanine aminotransferase should be suggested.

A Comparison of the Correlation of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) with Health-Related Quality of Life.

BACKGROUND AND AIM: The aim of this study was to compare the correlation of a recently developed systemic lupus erythematosus disease activity score (SLE-DAS) with the SLE disease activity index 2000 (SLEDAI-2K) with the Lupus Quality of Life questionnaire (LupusQoL) in Taiwanese patients with SLE. METHODS: A cross-sectional study was conducted in a regional teaching hospital in Taiwan from April to August 2019. Adult patients with a clinician-confirmed diagnosis of SLE based on the 1997 American College of Rheumatology revised criteria or the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria were recruited. SLE disease activity was measured with both SLEDAI-2K and SLE-DAS. Disease-specific quality of life was assessed using the LupusQoL. RESULTS: Of the 333 patients with SLE in this study, 90.4% were female and 40% were between the ages of 20 and 39 years. The median SLEDAI-2K score was 4.00 (interquartile range [IQR] 2.00-7.50) and the median SLE-DAS score was 2.08 (IQR 1.12-8.24) in our patients with SLE. After adjusting for sex and age intervals, both SLEDAI-2k and SLE-DAS were significantly and inversely associated with all eight domains of LupusQoL. The magnitudes of the mean absolute error, root mean square error, Akaike Information Criterion, Bayesian Information Criterion, and coefficient of determination were comparable between SLEDAI-2K and SLE-DAS. CONCLUSIONS: There were no clear differences in the use of SLE-DAS over SLEDAI-2K in assessing HRQoL in patients with SLE. We suggest that, in this aspect, both SLEDAI-2K and SLE-DAS are effective tools for measuring disease activity in patients with SLE.

Association of Traditional Chinese Medicine Body Constitution and Health-Related Quality of Life in Female Patients with Systemic Lupus Erythematosus: A Cross-Sectional Study.

BACKGROUND: Traditional Chinese medicine (TCM) body constitution has been studied in many diseases, but few have focused on systemic lupus erythematosus (SLE) and particularly their association with disease-specific quality of life (QoL). Therefore, the aim of this study was to investigate the association of TCM body constitution and QoL in female patients with SLE. METHODS: A cross-sectional study was conducted on adult female patients with a clinician-confirmed diagnosis of SLE in a regional hospital in Taiwan. TCM body constitution types were determined using the Constitution in Chinese Medicine Questionnaire (CCMQ). Disease-specific QoL of the participants was assessed using the LupusQoL. Multiple linear regression analyses were conducted to assess the associations between TCM body constitution types with the score of each of the eight domains of LupusQoL and between the numbers of multiple unbalanced body constitution types and score of each of the eight domains of LupusQoL. RESULTS: Of the 317 female patients with SLE, 22 (6.9%) were classified to have a gentleness balanced body constitution type. Among the remaining 295 patients with unbalanced body constitution types, Qi-deficiency was the most common (64.4%), followed by Yin-deficiency (57.6%). Multiple linear regression analyses showed that Qi-deficiency was significantly associated with the emotional, pain, and fatigue domains of the LupusQoL, whereas Yin-deficiency was significantly associated with the emotional and fatigue domains of the LupusQoL. In addition, all domains of the LupusQoL showed a general pattern of poorer QoL with increasing numbers of unbalanced body constitution types. CONCLUSIONS: Different TCM body constitution types were significantly associated with various domains of the LupusQoL. A high prevalence of multiple body constitution types in patients with SLE was observed. A consistent pattern of poorer LupusQoL with increasing numbers of unbalanced body constitution types was evident.

Association between clinical phenotypes of dermatomyositis and polymyositis with myositis-specific antibodies and overlap systemic autoimmune diseases.

ABSTRACT: The aim of this study was to evaluate the association between clinical phenotypes of dermatomyositis (DM) and polymyositis (PM) with myositis-specific antibodies (MSAs), and overlap diagnosis of systemic autoimmune diseases.This cross-sectional study was conducted on 67 patients with DM and 27 patients with PM recruited from a regional hospital in southern Taiwan. Clinical phenotypes of DM and PM were assessed and MSAs were measured using a commercial line blot assay. The association of clinical phenotypes of DM and PM with MSAs and overlap diagnosis of systemic autoimmune diseases was performed using univariate and multiple logistic regression analyses.Clinically, patients with DM and PM and overlap diagnosis of systemic sclerosis were associated with a higher risk of interstitial lung diseases (ILDs) (odds ratio [OR] = 6.73; P = .048), Raynaud phenomenon (OR = 7.30; P = .034), and malignancy (OR = 350.77; P = .013). The risk of malignancy was also associated with older age (OR 1.31; P = .012), and male patients were associated with a higher risk of fever. For MSAs, anti-aminoacyl-tRNA synthetase antibodies were associated with ILD, antinuclear antibody were associated with a lower risk of arthritis, anti-transcription intermediary factor 1-gamma antibodies were associated with milder symptoms of muscle weakness, anti-Ku antibodies were associated with overlap diagnosis of systemic lupus erythematosus, and anti-Ro52 antibodies were associated with the development of Raynaud phenomenon and Sjögren syndrome.MSAs and overlap diagnosis of systemic sclerosis were significantly associated with clinical phenotypes of DM and PM. Physicians should be vigilant for malignancy in older DM and PM patients with overlap diagnosis of systeic sclerosis. The possibility of developing ILD in patients with overlap diagnosis of systemic sclerosis or serum positivity of anti-aminoacyl-tRNA synthetase antibodies should be considered.

Applying Data Mining Techniques for Predicting Prognosis in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systematic chronic inflammatory disease. The disease mechanism remains unclear and may have resulted from autoimmune problems caused by genetic predisposing and pathogen infection. In clinical practice, selection of the initial treatment is based on the degree of disease activity, and treatment plans will be added gradually according to increased severity of the disease. However, treatment results can be unclear and treatment process uncertain and ambiguous, which can cause healthcare quality to become worse. This study attempts to combine expert opinions to construct various classifiers using a number of data mining techniques to analyze the different prognosis of two patient groups, by predicting whether the inflammatory indicator erythrocyte sedimentation rates of these two groups will be within the normal range with different medication strategies. Clinical data were collected for construction of different classifiers and we evaluate the prediction accuracy rate of each classifier afterwards. The optimum prediction model is selected from these classifiers to predict the prognosis of RA within these treatment strategies and analyze various results. The results show the accuracy rate of the prediction model by Logistic, SVM and DT module were 0.7927, 07829 and 0.9094, respectively. In the RA complications dataset, the accuracy rate of were 0.9393, 0.9290 and 0.9812, respectively. Futhermore, gain ratio was used to further analyze the rules and to discover which branch nodes are the most importance factor. The results of this study are helpful for formulation and development of guidelines for clinical RA treatments, and implementation of a decision support system by using the prediction model can assist medical staff to make correct decisions in the disease's early stage.

Risk factors, including different biologics, associated with depression and anxiety in patients with rheumatoid arthritis: a cross-sectional observational study.

BACKGROUND: To evaluate the associated factors of depression and anxiety in patients with rheumatoid arthritis (RA) and examine the effect of different biologics. METHODS: This cross-sectional study was conducted in a regional hospital in southern Taiwan from August of 2017 to April of 2018. A total of 625 patients with RA were included. RA disease activity was measured with Disease Activity Score over 28 joints based on erythrocyte sedimentation rate (DAS28-ESR). Depression and anxiety were measured with Hospital Anxiety and Depression Scale (HADS). RESULTS: Based on HADS scores, 38 subjects (6.1%) and 15 subjects (2.4%) were classified as depression and anxiety, respectively. Increased disease activity of RA is noted in RA patients with depression or anxiety, and among the items of DAS28-ESR, only the two subjective components: tender joint count over 28 joints (TJC28) and patient's global assessment (PGA) were significantly different. Multiple logistic regression analysis indicated that depression was significantly associated with TJC28 (adjusted odds ratio [aOR] = 1.10, 95% confidence interval [CI] 1.05-1.14) and female (aOR = 5.43, 95% CI 1.25-23.52); and anxiety was associated with TJC 28 (aOR = 1.07, 95% CI 1.00-1.15) and PGA (aOR = 1.03, 95% CI 1.01-1.06). Secondary analysis found a significantly lower risk of depression (aOR = 0.20, 95% CI 0.04-0.88) in patients receiving etanercept, but not anxiety, when compared with the non-biologic group. CONCLUSIONS: This study suggests that only subjective components of DAS28-ESR were significantly associated with depression and anxiety. In comparison with other biologics, patients receiving etanercept appeared to have a lower risk of depression.Key Points• Rheumatoid arthritis patients possessed higher risk of depression and anxiety.• Both depression and anxiety are strongly correlated with the subjective components of DAS28-ESR.• Etanercept might be the choice of biologics in rheumatoid arthritis patients with depression.

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg-/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis.

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg-/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg-/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1-4 years after the first dose of RTX and 0.5-1.5 years after the last one. In HBsAg-/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)- at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg-/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

HLA haplotype A33-B58-Cw10 may modulate radiographic development of bamboo spine in Taiwanese patients with primary ankylosing spondylitis.

OBJECTIVE: To evaluate the possible relationship between HLA alleles and bony ankylosis of the spine (bamboo spine) in Taiwanese patients with ankylosing spondylitis (AS). METHODS: A small cohort of HLA-B27 positive AS patients was conducted to analyze the effects of alleles {and haplotypes} on the development of bamboo spine. DNA typing of HLA class I and class II genes were performed by SSP method on primary ankylosing spondylitis patients with bamboo spine (n = 84) and spinal enthesopathy controls (n = 228). Odds ratios with 95% confidence intervals and P value were estimated. Determination of the most probable HLA haplotypes on all patients were constructed by comparison of the alleles carried by each patient with the HLA haplotype database established in Taiwanese population studies using homozygosity approach [1] and by expectation-maximum algorithm [2]. RESULTS: Allele frequencies of HLA A33, B58, Cw10, DR4, DR17 and DQ2 were significantly lower in bamboo patients as compared to non-bamboo controls. In contrast, allele frequencies of A24, B54, Cw15, DR11 and DR14 were significantly higher in bamboo patients. Less remarkably, high frequencies of B39, B51, Cw1 and Cw2 alleles were also noted in bamboo patients. Considering linkage disequilibria of alleles in haplotypes, HLA-A11-B27-Cw12 was the most common haplotype in both bamboo and non-bamboo groups (95.23% vs. 91.22%, respectively, P = 0.238). {Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17} were significantly lower in bamboo patients as compared to those in controls (P < 0.001, P = 0.001, P = 0.002, respectively). CONCLUSION: Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 showed a strong association with bamboo spine in Taiwanese AS patients. Detection of such haplotypes might be a great aid in the management of patients with the disease.

Factors associated with disease-specific quality of life in Taiwanese patients with ankylosing spondylitis: a cross-sectional study.

OBJECTIVE: The aim of this study was to assess the factors associated with disease-specific quality of life in Taiwanese patients with ankylosing spondylitis. DESIGN: A cross-sectional study. SETTING: A regional teaching hospital in southern Taiwan. PARTICIPANTS: Adult patients with ankylosing spondylitis recruited from the outpatient rheumatology clinics of the study hospital. PRIMARY OUTCOME MEASURE: Disease-specific quality of life assessed by the Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL). RESULTS: Of the 265 patients, 57% were 20-49 years of age, with a male preponderance (75.5%). Multiple stepwise linear regression analysis indicated that a higher disease activity, assessed by the Ankylosing Spondylitis Disease Activity Score, was significantly and independently associated with a lower quality of life in all four domains (physical function, disease activity, emotional well-being and social participation) of the EASi-QoL. In addition, various independent factors, including educational level, nature of occupation, disease duration, dietary habit and body mass index, were significantly associated with different domains of the EASi-QoL. CONCLUSIONS: Our findings indicated that, in addition to disease activity and perceived health status, a number of other factors could significantly impact the different aspects of quality of life in patients with ankylosing spondylitis, which warrant special consideration and support from healthcare providers.