Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis in patients with systemic lupus erythematosus.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have an increased risk of vascular thrombosis compared to the general population. Therefore, biomarkers for predicting the risk of thrombosis in patients with SLE are needed. METHODS: In the present study, a total of 66 patients with SLE (22 with and 44 without a history of thrombosis) were enrolled. The cases with thrombosis and the controls without thrombosis were matched for age (± 5 years) and sex. We assessed ADAMTS13 activity, D-dimer levels, and antiphospholipid antibodies. Clinical manifestations, SLE disease activity, classical risk factors, and medical history were collected. RESULTS: ADAMTS13 activity was significantly reduced, and D-dimer levels were significantly increased in patients with SLE with a history of thrombosis compared with those in patients without thrombosis. Receiver operating characteristic curve analysis revealed a good correlation between reduced ADAMTS13 activity and a history of thrombosis. Reduced ADAMTS13 activity was correlated with increased D-dimer levels only in the thrombotic group. CONCLUSION: Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis and may serve as prognostic markers for thrombosis in patients with SLE.

Humoral Immunogenicity of mRNA Booster Vaccination after Heterologous CoronaVac-ChAdOx1 nCoV-19 or Homologous ChAdOx1 nCoV-19 Vaccination in Patients with Autoimmune Rheumatic Diseases: A Preliminary Report.

Immunogenicity data on the mRNA SARS-CoV-2 vaccine booster after completing a primary series vaccination, other than the mRNA vaccine, in patients with autoimmune rheumatic diseases (ARDs) is scarce. In this study, we reported the humoral immunogenicity of an mRNA booster 90-180 days after completing heterologous CoronaVac/ChAdOx1 nCoV-19 (n = 19) or homologous ChAdOx1 nCoV-19 (n = 14) vaccination by measuring the anti-SARS-CoV-2 receptor binding domain (RBD) IgG levels at one and three months after mRNA booster vaccination. This study included 33 patients with ARDs [78.8% women; mean (SD) age: 42.9 (10.6) years]. Most patients received prednisolone (75.8%, mean [IQR] daily dose: 7.5 [5, 7.5] mg) and azathioprine (45.5%). The seropositivity rates were 100% and 92.9% in CoronaVac/ChAdOx1 and ChAdOx1/ChAdOx1, respectively. The median (IQR) anti-RBD IgG level was lower in the ChAdOx1/ChAdOx1 group than in the CoronaVac/ChAdOx1 group (1867.8 [591.6, 2548.6] vs. 3735.8 [2347.9, 5014.0] BAU/mL, p = 0.061). A similar trend was significant in the third month [597.8 (735.5) vs. 1609.9 (828.4) BAU/mL, p = 0.003]. Minor disease flare-ups occurred in 18.2% of the patients. Our findings demonstrated satisfactory humoral immunogenicity of mRNA vaccine boosters after a primary series, with vaccine strategies other than the mRNA platform. Notably, the vaccine-induced immunity was lower in the ChAdOx1/ChAdOx1 primary series.

Thai Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Outcomes and Risk Factors for Mortality.

BACKGROUND/OBJECTIVE: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) have an increased risk of premature death. Different subtypes, predictors, and ethnicities may affect the overall survival. However, the overall survival of Thai AAV patients has not been reported. We examined the mortality and prognosis of these patients. METHODS: This medical record review study included adult AAV patients, admitted to Songklanagarind Hospital from 2007 to 2017. Antineutrophil cytoplasmic antibody-associated vasculitis was diagnosed according to the 1990 American College of Rheumatology criteria or 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Follow-up data were collected until June 2018. Prognostic factors and overall survival were analyzed. RESULTS: Among 57 AAV patients, mean (SD) age was 49.3 (16.1) years. Microscopic polyangiitis was the predominant diagnosis (42%). Kidneys (67%) and lungs (65%) were the 2 most affected organs. Initial Birmingham Vasculitis Activity Score (BVAS) greater than 20 was found in 61% of patients. Corticosteroids were the main drugs, and 58% received cyclophosphamide during the induction phase. Overall mean survival time was 38.8 (42.2) months. Patient survival was 91% and 82% at 1 and 6 months, respectively. One-year and 5-year survival rates were 78% and 63%, respectively. Univariate analysis showed that initial BVAS of greater than 20, neutrophil-to-lymphocyte ratio greater than 5.8, and need for invasive ventilator were significant predictors of mortality. Initial BVAS of greater than 20 was the only predictor of death in multivariate analyses (odds ratio, 4.22; 95% confidence interval, 1.01-17.63; p = 0.048). CONCLUSIONS: The mortality rate of Thai AAV patients is high and strongly related to high disease activity. An early recognition and referral system are warranted to improve outcomes.

Prevalence and associated factors of medication nonadherence among Thai patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic disease requiring complex treatment strategies to prevent disease flare ups and to reduce hospitalizations. Medication adherence is the main concern for improving patient outcomes. Although various studies on medication nonadherence for SLE have been conducted, no definite conclusions have been reached. OBJECTIVE: To quantify the prevalence of medication nonadherence among patients with SLE and to analyse the associated factors. METHODS: A prospective, self-reported questionnaire study was conducted in Songklanagarind Hospital. Patient aged 18 years or older, who had an established diagnosis of SLE, and who had been receiving medications for at least 6 months, were included in the study. Medication adherence was assessed through a visual analogue scale (VAS) and through the medication-taking behaviour measure for Thai patients (MTB-Thai) scale. RESULTS: One hundred and seventy-two SLE patients were enrolled in the study. Most SLE patients were young to middle aged (56.40%) and had no clinical disease activity (67.4%), as assessed by a clinical SLEDAI score. Nonadherence rates were 32% and 25.3% by VAS and the MTB-Thai scale, respectively. Patients aged 55 years or older, who used the universal coverage of health care system, who used multiple medications (>10 pills/day), and who had a good attitude towards the disease were associated with a low risk of nonadherence. CONCLUSION: Up to 25% SLE patients poorly adhered to their prescriptions. Age, reimbursement scheme, pill number, and attitude towards SLE were associated with nonadherence in our patients with SLE.

Erythematous auricular papules in the fatal cases of anti-MDA5 antibody-positive interstitial lung disease.

INTRODUCTION/OBJECTIVES: The anti-melanoma differentiation-associated gene 5 (Anti-MDA5) antibody is associated with rapidly progressive interstitial lung disease (RP-ILD) and clinically amyopathic dermatomyositis (CADM). The predictors of treatment response would help in classifying the subgroups and decision-making. Here, we aimed to report an observational skin lesion that might be associated with a grave prognosis in six patients with anti-MDA5 antibody-positive ILD. METHODS: This case series included 6 anti-MDA5 antibody-positive ILD patients, who were admitted to Songklanagarind Hospital between January 2018 and June 2020. Their medical records were reviewed for clinical phenotypes, laboratory results, imaging studies, treatment, and outcomes. The cutaneous manifestations associated with fatal outcomes were observed and reported. RESULTS: Among 6 patients with anti-MDA5 antibody-positive ILD, 5 patients had CADM and one patient had no skin involvement. Four patients manifested as RP-ILD within a few months. Three deaths occurred despite highly intensive immunosuppressive treatment. All the patients in the dead group exhibited erythematous papules on their auricles and a presence of pulmonary consolidation at lower lung fields was additionally observed. CONCLUSION: Erythematous auricular papules may be a hallmark of grave prognosis in anti-MDA5 positive CADM with ILD.

Prevalence and risk factors of strongyloidiasis in patients with systemic lupus erythematosus in Southern Thailand.

Background: Strongyloidiasis can be fatal in systemic lupus erythematosus (SLE) patients, but few epidemiological studies have investigated the burden of this tropical disease among the SLE population. This study aimed to assess the prevalence and associated factors of strongyloidiasis among SLE patients in Southern Thailand. Methods: A cross-sectional study was conducted on 180 SLE patients attending the Rheumatology Clinic at Songklanagarind Hospital. Stool specimens were collected and examined using the direct smear technique and agar plate culture technique. Serum anti-Strongyloides stercoralis IgG was measured by IgG-ELISA. Results: The overall prevalence of strongyloidiasis by combined parasitologyl and/or serology was 15.6%. The prevalence of strongyloidiasis by parasitological methods was 2.2%. Positive parasitology and/or serology was associated with male sex and a SLE disease duration of less than two years. Conclusion: Strongyloidiasis is highly prevalent among the SLE population. A combination of serological and parasitological methods increases the rate of diagnosis of strongyloidiasis in SLE patients.

Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response to methotrexate: a pilot randomized, double-blind, placebo-controlled add-on trial.

OBJECTIVE: To evaluate the efficacy and safety of diacerein in patients with rheumatoid arthritis (RA) who are methotrexate inadequate responders (MTX-IR). METHOD: In this pilot, multicenter, double-blind, placebo-controlled trial, MTX-IR RA patients were randomized to either diacerein or matching placebo as add-on treatment to MTX for 24 weeks. Efficacy and safety were evaluated every 4 weeks until week 28. Primary and secondary efficacy endpoints were the percentage of patients achieving the ACR20 criteria and a moderate EULAR response at week 24, respectively. RESULTS: Forty patients were equally randomized to both study treatments; 16 and 19 participants completed the study in the diacerein and the placebo arms, respectively. Baseline characteristics were similar in both groups, except that tender joint count, DAS28-ESR score, and non-steroidal anti-inflammatory drug consumption were higher in the placebo arm. The ACR20 response at week 24 was similar in the diacerein and placebo groups (65% vs 45%, P = .20). However, treatment response according to the EULAR criteria was better in patients taking diacerein (75% vs 25% of moderate response, P = .002). In the 35 patients with assessments through week 28, diacerein was superior to placebo in ACR20 at weeks 24 and 28 (both 81% vs 47%, P = .04). Incidence of adverse events was comparable in both arms, with only chromaturia being more common with diacerein than placebo (40% vs 10%, P = .03). CONCLUSIONS: These preliminary results show the potential benefits of diacerein on pain, joint function, and disease activity in MTX-IR RA patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01264211 Key Points • Diacerein has shown positive effects on rheumatoid arthritis symptoms. • A good safety profile of diacerein has been observed when it was administered as add-on therapy to methotrexate in patients with rheumatoid arthritis.

Effectiveness and Drug Survival of Anti-Tumor Necrosis Factor α Therapies in Patients With Spondyloarthritis: Analysis From the Thai Rheumatic Disease Prior Authorization Registry.

OBJECTIVE: This study aimed to evaluate the long-term effectiveness and safety of the first anti-tumor necrosis factor α therapy (TNFi) and to identify the associated factors of drug discontinuation in patients with spondyloarthritis. METHODS: This was a medical records review study. Patients with spondyloarthritis who were prescribed the first TNFi between December 2009 and October 2014 in the Rheumatic Disease Prior Authorization registry were enrolled. Baseline clinical data were retrieved. The Cox proportional hazards model was used to identify factors associated with discontinuation of drugs. RESULTS: Among 138 patients, 97 had ankylosing spondylitis (AS), and 41 had psoriatic arthritis (PsA). The effectiveness of TNFi in AS and PsA was 55% to 59% at 4 months and 75% to 96% at 3 years, as measured by a 50% decrease in the Bath Ankylosing Spondylitis Disease Activity Index from baseline. For PsA with peripheral arthritis, improvement of the joint count by 50% was observed in 61.8% of patients at 4 months and 100% at 3 years. Survival from TNFi was 63% for AS and 56% for PsA at 3 years. For AS, the factors associated with good response leading to discontinuation of TNFi were baseline patient global assessment 3 to 6/10 (hazard ratio [HR], 6.3) and the use of leflunomide (HR, 6.0) and infliximab (HR, 4.8). A good response (38.5%) was the most common cause of discontinuation of the first TNFi, followed by toxicity (28.2%), nonadherence (20.5%), and lack of effectiveness (12.8%). CONCLUSIONS: Ankylosing spondylitis and PsA responded well to TNFi during the 3-year follow-up. The retention rate was approximately 60% for AS and PsA. A good response to the first TNFi was the most common reason for discontinuation.

Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry.

AIM: To evaluate and compare the retention rate of biological disease-modifying antirheumatic drugs (bDMARDs) in real-life practice and identify risk factors related to remission and drug discontinuation in patients with rheumatoid arthritis (RA). METHOD: A total of 256 patients fulfilling criteria for RA and starting bDMARD between December 2009 and October 2014 were selected from the Rheumatic Disease Prior Authorization registry. Baseline demographic and clinical data were recorded. The cumulative probability of bDMARD discontinuation over 5 years of follow-up and factors associated with RA remission and bDMARD withdrawal were analyzed. RESULTS: Almost half (46%) of patients were initially treated with rituximab (RTX), with 33% treated with etanercept (ETN) and 21% with infliximab (IFX). Fewer than 10% were subsequently switched to a second bDMARD. The 1- and 5-year remission rates in patients continuing their first bDMARD were 7.2% and 21.5%, respectively. At 5 years, the drug survival rates for RTX, ETN and IFX were 50%, 25% and 22%, respectively. Multivariate analysis showed that RTX was significantly associated with highest drug survival. Relative to RTX, the hazard ratios for discontinuation of IFX and ETN were 2.60 (95% confidence interval [CI] 1.53-4.42) and 2.15 (95% CI 1.36-3.42), respectively. Thirty-nine percent of patients stopped treatments, due to inadequate response (42%), serious adverse events (22%), nonadherence (14%) or remission/low disease activity (13%). CONCLUSION: Over 5 years, only one-third of patients continued using their first bDMARD. The leading cause of drug discontinuation was inadequate response.

2016 updated Thai Rheumatism Association Recommendations for the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

AIM: In June 2015, the Thai Rheumatism Association (TRA) approved an update of its recommendation for the use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic (tsDMARD) in the treatment of rheumatoid arthritis (RA) to cover those currently available in Thailand (etanercept, infliximab, golimumab, rituximab, tocilizumab, abatacept and tofacitinib). METHOD: A search of the literature was performed between January 2000 and June 2015. Existing RA recommendations, in relation to the use of bDMARDs and tsDMARD, were identified and evaluated by the AGREE II instrument prior to their use as a 'guide' for developing this TRA recommendation. An additional literature search was performed in order to answer specific clinical questions that could not be found in existing guidelines. RESULT: Thirteen recommendations were developed. They covered the use of RA classification criteria, the aim of RA treatment, when to initiate bDMARDs/tsDMARD or taper or switch them to other medications, as well as monitoring these drugs during their use. In addition, specific issues including their use and vaccination, malignancies, pregnancy and lactation, and perioperative period also were addressed. Public hearings were performed at the annual meeting of the TRA and of the Royal College of Physicians of Thailand. The recommendations were distributed to other professional associations related to RA management, as well as government sectors associated with the reimbursement policy, prior to development of the final version. CONCLUSION: These recommendations will help Thai rheumatologists prescribe bDMARDs and tsDMARD more appropriately when treating RA patients.

Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis for non-rheumatologists: Integrating systematic literature research and expert opinion of the Thai Rheumatism Association.

AIM: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS: Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS: A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS: These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient.

Apolipoprotein B as an independent predictor of arterial stiffness in systemic lupus erythematosus patients.

AIM: To determine the relationship of apolipoprotein B (Apo-B) and arterial stiffness determined by brachial-ankle pulse wave velocity (baPWV) in systemic lupus erythematosus (SLE) subjects. METHODS: Eighty-seven Thai SLE subjects with inactive disease activity were studied. Fasting blood was collected for creatinine, glucose, lipid profiles, Apo-B and Apo-A1. Pearson correlation and stepwise-linear regression were used for the analysis. RESULTS: The mean age of the subjects was 36.69 ± 10.85 years; 6.90% of them had stage 3 or more severe chronic kidney disease, 49.40% took anti-hypertensive drugs and 4.60% had abnormal glucose metabolism. The mean value for baPWV was 1332 ± 274.12 cm/s. Thirty-six percent of the subjects had increased arterial stiffness with mean Apo-B levels of 1.05 ± 0.31 g/L compared to 0.94 ± 0.24 in normal arterial stiffness. There were correlations of baPWV with age, systolic blood pressure (BP), diastolic BP and creatinine clearance. Apo-B tended to be associated with baPWV (P = 0.06) whereas low-density lipoprotein cholesterol did not (P = 0.2). By multiple regression analysis, systolic BP, age and Apo-B were the significant predictors of baPWV. CONCLUSION: Apo-B was independently associated with arterial stiffness in SLE subjects.

Comprehensibility, reliability, validity, and responsiveness of the Thai version of the Health Assessment Questionnaire in Thai patients with rheumatoid arthritis.

INTRODUCTION: The Health Assessment Questionnaire Disability Index (HAQ-DI) is a commonly used instrument to assess functional status of patients with rheumatoid arthritis (RA). Translations and adaptations of the HAQ-DI have been carried out for use with RA patients in several countries. The objective of this study was to evaluate the psychometric properties of the Thai version of the HAQ-DI (Thai HAQ) in Thai patients with RA. METHODS: Comprehensibility of the Thai HAQ was assessed by 126 patients with RA from 6 medical centers in Thailand. Another group of 115 patients with active RA was enrolled to test the reliability (internal reliability and 1-week test-retest reliability), construct validity (correlations with other measures of RA disease activity), floor and ceiling effects, and sensitivity to change of the Thai HAQ at 3 months of treatment with disease-modifying antirheumatic drugs. RESULTS: More than 98% of the patients regarded the Thai HAQ as comprehensible. The internal consistency of the Thai HAQ was satisfactory with the overall Cronbach alpha of 0.91. The test-retest reliability of the Thai HAQ was acceptable with the intraclass correlation coefficient of 0.89. Moderate correlations between the Thai HAQ and other outcomes of RA disease activity were observed, except erythrocyte sedimentation rate, with the Spearman correlation coefficients ranging from 0.42 to 0.57. The responsiveness of the Thai HAQ was moderate, with a standardized response mean of 0.75 (95% confidence interval 0.56 to 0.94). CONCLUSIONS: The Thai HAQ is comprehensible, reliable, valid and sensitive to change in the evaluation of functional status of Thai patients with RA. The Thai HAQ is an essential tool to measure treatment effects and progression of disability in RA patients and should be applied in both clinical trials and routine clinical care settings.