Prevalence of cognitive impairment and cognitive improvement in patients with systemic lupus erythematosus during a 6-month follow-up study.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a simple and reliable screening tool for early detection for cognitive impairment in systemic lupus erythematosus (SLE). Most previous studies were cross-sectional with small samples. Research on long-term cognitive changes and reversibility is limited. This study aimed to establish the prevalence of cognitive impairment and changes in SLE patients after 6 months and the associated factors. METHODS: A prospective study was conducted in 200 patients with SLE between April 2021 and March 2022. Demographic data, disease activity, and medications were recorded. MoCA was administered at baseline and 6 months; for Thais, scores 17-24 indicate mild cognitive impairment, while ≤16 signifies severe impairment. Multivariate analysis identified factors associated with cognitive impairment and improvement. RESULTS: The patients' median age was 44 years (range: 19-73), 96% were female, and 55% had < 12 years of education. The median disease duration was 11 years (range: 0-51.8), and 79% of patients had inactive disease. Cognitive impairment was found in 70% of patients (mild, 63%; severe, 7%). The most often affected domains were delayed recall (82%), abstraction (80.5%), language (76%) and visuospatial/executive function (70.5%), whereas orientation and naming were the least involved. Factors significantly associated with cognitive impairment were age > 40 years (OR, 3.71; 95% CI, 1.72-8.00), formal education < 12 years (OR, 3.11; 95% CI, 1.45-6.63), and prednisolone use (OR, 2.21; 95% CI, 1.08-4.51). Sixty-six (38.2%) of 173 patients completing the 6-month re-evaluation exhibited cognitive changes (52 [30.1%] improved; 14 [8.1%] deteriorated). Except for delayed recall, all commonly affected domains showed significant improvement. Disease activity, prednisolone, antimalarials, or immunosuppressant use did not predict cognitive improvement. CONCLUSIONS: Mild cognitive impairment is prevalent among patients with SLE. Due to the possibility of reversibility, early recognition and additional research to identify relevant factors are required.

Relationship Between Health-Related Quality of Life and Patient Acceptable Symptom State With Disease Activity and Functional Status in Patients With Ankylosing Spondylitis in Thailand.

OBJECTIVE: This study aimed to identify factors associated with EuroQoL-5 Dimensions, 5 Levels and Patient Acceptable Symptom State (PASS) and health utility (HU) in Thai patients with ankylosing spondylitis (AS). METHODS: This was a cross-sectional study of consecutive AS patients visiting Siriraj Hospital between May 31, 2012, and March 31, 2016. Demographic data and outcomes related to HU (Thai version of EuroQoL-5 Dimensions, 5 Levels), disease activity (Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate or Ankylosing Spondylitis Disease Activity Score-C-reactive protein, number of tender and swollen joints, and enthesitis), and functional status (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire) were collected. Regression analysis was used to explore factors associated with each EuroQOL-5 Dimensions (EQ-5D) domain, HU, and PASS. RESULTS: Among 119 AS patients, the mean age was 40.4 years; 61.3% were male. The mean EQ-5D was 0.75. In univariate analysis, lower disease activity and less impaired function were significantly associated with higher HU and not to mild problems in each EQ-5D domain. In multivariate regression analysis, Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein, and Health Assessment Questionnaire adjusting for age explained 77.4% of the HU variance. Patients answering yes to PASS were significantly older, had higher HU, and lower disease activity compared with those answering no to PASS. Usual activity and pain problems were importantly related to PASS after adjusting for other domains and age. CONCLUSIONS: Disease activity and functional status in AS patients were significant factors related to HU and PASS. To improve quality of life, treatment goals should be achieving remission, improving function, and controlling pain.

Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis.

The objective of this study was to investigate the association of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status with disease progression and treatment outcomes in patients with rheumatoid arthritis (RA). A total of 276 adult patients who fulfilled the American College of Rheumatology 1987 classification criteria for RA were recruited from the Rheumatology clinic, Siriraj Hospital, from January 2011 to December 2012. Demographic, clinical, and laboratory data were collected at baseline and every 3 months up to 1 year of follow-up. RF and ACPA were measured at baseline. Radiography of the hands and feet was performed at baseline and 1 year. Patients with RF+/ACPA+ had significantly more severe disease activity and impaired functional status than those who had RF-/ACPA-. Although they received more aggressive treatment with methotrexate and combination of non-biologic, disease-modifying antirheumatic drug than other groups, fewer patients in this group achieved remission at 1 year of follow-up, especially when compared to RF-/ACPA- group (12 vs. 18 %). For radiographic erosion, patients with the presence of either RF or ACPA had a higher proportion of hand erosion than seronegative patients at baseline (77, 73, 83, and 32 %, p < 0.001 for RF+/ACPA+, RF+/ACPA-, RF-/ACPA+, and RF-/ACPA-, respectively). After 1 year of follow-up, patients who developed new erosion at the hands were more prevalent in RF+/ACPA+ (32 %) and RF+/ACPA- (33 %) groups. However, "newly developed" feet erosion was most common in RF+/ACPA- group (40 %) than in other groups. Patients with positive either RF or ACPA or both have more severe and aggressive disease that requires intensive treatment to improve outcomes.

Safety and effectiveness of intravenous CT-P13 in inflammatory arthritis: post-marketing surveillance study in Thailand.

Background: The infliximab biosimilar CT-P13 was approved in Thailand in 2015. Methods: This open-label, multicenter, post-marketing surveillance study evaluated the safety (events of special interest [ESIs]; primary end point) and effectiveness of 46 weeks of CT-P13 treatment according to routine practice in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA), with 1 year follow-up post-treatment. Results: 30 patients were enrolled (16 RA, 8 AS and 6 PsA). Infections were the most frequently reported study drug-related ESIs (2 RA and 2 AS). One patient with RA and one with PsA experienced infusion-related reactions. No cases of tuberculosis, malignancy (as expected, given 1 year follow-up), or drug-induced liver disease were reported. Disease activity improved across indications. Conclusion: CT-P13 was well tolerated and effective across indications.

Infliximab is one biological medicine used to treat inflammatory diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). CT-P13 is a near-identical copy, called a biosimilar, of the original ('reference') version of infliximab. CT-P13 is the first biosimilar to receive regulatory approval for treatment of the same three diseases from the European Medicines Agency (EMA) and US Food and Drug Administration. Biosimilarity means that CT-P13 does not differ from the original version of infliximab in clinically important ways, such as how safe it is and how well it works. CT-P13 and reference infliximab provided similar symptom relief during previous clinical trials, and both drugs caused similar side effects. It is important to monitor the safety and performance of CT-P13 when given during routine clinical practice, and in different ethnic populations, such as through the study reported here. Following regulatory approval in Thailand, 30 patients prescribed CT-P13 during routine clinical practice participated in this study. The study included 16 patients with RA, eight with AS and six with PsA. The patients took CT-P13 for 46 weeks and were monitored for a further year. Side effects of CT-P13 were as expected based on previous experience and did not raise any safety concerns. Based on the known safety profile of CT-P13, the study looked at some side effects in particular: infections were the most common of these side effects, experienced by 16 patients overall (seven patients with RA, five patients with AS and four patients with PsA). CT-P13 improved symptoms for all of the diseases. The study suggests that CT-P13 can be given safely and reduces symptoms in Thai patients with AS, RA or PsA. Thai Clinical Trials Registry: TCTR20170817005 (www.thaiclinicaltrials.org/show/TCTR20170817005).

Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis has manifestations in various organs including ophthalmic involvement. The present study evaluates prevalence of dry eye and secondary Sjogren's syndrome using salivary scintigraphy which has not been used in previous reports. OBJECTIVE: To evaluate the prevalence of secondary Sjogren's syndrome in patients with rheumatoid arthritis, including clinical characteristics and dry eye, compared with non-Sjogren's syndrome. DESIGN: Descriptive cross sectional study MATERIAL AND METHOD: Sixty-one patients with rheumatoid arthritis were recruited at Siriraj Hospital during March 2009-September 2010 and filled in the questionnaires about dry eye for Ocular Surface Disease Index (OSDI) with a history taking of associated diseases, medications, duration of symptoms of dry eyes and dry mouth. The Schirmer I test without anesthesia, tear break-up time, rose bengal staining score, severity of keratitis and salivary scintigraphy were measured and analyzed. RESULTS: Prevalence of secondary Sjogren's syndrome and dry eye were 22.2% (95% CI 15.4 to 30.9) and 46.7% (95% CI 38.0 to 55.6), respectively. Dry eye interpreted from OSDI, Schirmer 1 test, tear break-up time and rose bengal staining was 16.4%, 46.7%, 82% and 3.3% respectively. Fifty-two percent of patients had a history of dry eye and dry mouth with mean duration 27.4 and 29.8 months, respectively. Superficial punctate keratitis and abnormal salivary scintigraphy were found in 58.2% and 77.8%. Duration of rheumatoid arthritis, erythrocyte sedimentation rate were not correlated with secondary Sjogren's syndrome. Dry eye from OSDI with secondary Sjogren's syndrome (33.3%) compared with non-Sjogren's syndrome (9.5%) was significant difference (p = 0.008). Adjusted odds ratio for secondary Sjogren's syndrome in OSDIL score > 25 was 13.8 (95% CI 2.6 to 73.8, p = 0.002) compared to OSDI score < 25. CONCLUSION: Awareness and detection of dry eye syndrome and secondary Sjogren's syndrome in rheumatoid arthritis was crucial for evaluation of their severity and proper management.

Antimalarial-induced maculopathy: accuracy of Amsler grid as a diagnostic tool and risk factors.

OBJECTIVE: To determine the sensitivity, specificity, and agreement of Amsler grid (AG) in detecting antimalarial induced maculopathy (AM) compared to combination of dilated ocular examination and Humphrey visual field (HVF) 10-2 and to estimate the risk factors of AM. MATERIAL AND METHOD: 20 patients with AM and 20 patients with no AM were included between October 1, 2010 and June 30, 2011 in Siriraj Hospital, Thailand. Sensitivity, specificity and unweighted kappa were used to determine accuracy of AG. Logistic regression was used to explore risk factors associated with AM. RESULTS: The sensitivity and specificity of AG were 40% and 100%, respectively. The agreement of AG and HVF 10-2 was poor with kappa of 0.4. Creatinine clearance < 60 ml/min/1.73 m2 and bilateral macular abnormality were associated with AM at the same odds ratio of 8.9 (95% confidence interval: 1.3 to 61.2). CONCLUSION: AG may be used as an additional test between ocular evaluation visits providing the availability and low cost. Patients with renal impairment and bilateral macular abnormality are associated with AM.

Can we predict final outcome of internal medicine residents with in-training evaluation.

OBJECTIVE: To assess the predictive value of in-training evaluation for determining future success in the internal medicine board certifying examination. MATERIAL AND METHOD: Ninety-seven internal medicine residents from Faculty of Medicine Siriraj Hospital who undertake the Thai Board examination during the academic year 2006-2008 were enrolled. Correlation between the scores during internal medicine rotation and final scores in board examination were then examined. RESULTS: Significant positive linear correlation was found between scores from both written and clinical parts of board certifying examination and scores from the first-year summative written and clinical examinations and also the second-year formative written examination (r = 0.43-0.68, p < 0.001). Monthly evaluation by attending staffs was less well correlated (r = 0.29-0.36) and the evaluation by nurses or medical students demonstrated inverse relationship (r = -0.2, p = 0.27 and r = -0.13, p = 0.48). CONCLUSION: Some methods of in-training evaluation can predict successful outcome of board certifying examination. Multisource assessments cannot well extrapolate some aspects of professional competences and qualities.

Budget Impact of Sequential Treatment with Biologics, Biosimilars, and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Thai Patients with Rheumatoid Arthritis.

BACKGROUND: Targeted treatment of rheumatoid arthritis (RA) includes biological DMARDs (bDMARDs) and JAK inhibitors (JAKi). These agents are recommended at the same level on the basis of their efficacy and safety data. However, no local evidence of the impact of RA treatment regimens on total budget spending is available to date. This study aimed to explore the budget impact of different sequential targeted treatments in Thai patients with RA who failed at least three conventional synthetic DMARDs. METHODS: We used the adapted model to evaluate the budget impact of adding tofacitinib in different order to RA targeted treatment regimens. The Thai RA population eligible for treatment was assessed on the basis of local prevalence and experts' opinion. Cost-impact analysis was evaluated for the treatment sequences of four different lines of targeted therapies using inputs like clinical efficacy, safety, and costs. The model used a decision tree structure with treatment nodes corresponding to treatment response outcomes for a cohort of patients. The comparisons included five bDMARDs [etanercept (ETN), infliximab (IFX), golimumab (GOL), rituximab (RTX), tocilizumab (TCZ) intravenous formulation], two JAKi [tofacitinib (TOF) and baricitinib (BAR)], and two IFX biosimilars (PF-06438179/GP1111 and CT-P13). A total of 80 treatment sequences within each containing four sequential first-, second-, third-, and fourth-line options were generated. RESULTS: The findings of the base case scenario indicated the treatment sequence with RTX as first-line, followed by IFX biosimilar (PF-06438179/GP1111), TOF, and TCZ, respectively, produced the lowest budget impact of US $693.54 million. Sensitivity analyses confirmed the robustness of our findings. CONCLUSION: The order of targeted therapy starting with RTX, then IFX biosimilar, TOF, and finally TCZ incurred the lowest budget impact over a 5-year time horizon for treating moderate to severe RA. Our findings may help payers and policy makers consider appropriate budget allocation on chronic non-communicable diseases, especially RA.

Autoantibody profiles and clinical association in Thai patients with autoimmune retinopathy.

Autoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to be involved in the pathogenesis. This retrospective cohort study assessed the antiretinal autoantibody profiles and their association with clinical outcomes of AIR patients in Thailand. We included 44 patients, 75% were females, with the overall median age of onset of 48 (17-74, IQR 40-55.5) years. Common clinical presentations were nyctalopia (65.9%), blurred vision (52.3%), constricted visual field (43.2%), and nonrecordable electroretinography (65.9%). Underlying malignancy and autoimmune diseases were found in 2 and 12 female patients, respectively. We found 41 autoantibodies, with anti-α-enolase (65.9%) showing the highest prevalence, followed by anti-CAII (43.2%), anti-aldolase (40.9%), and anti-GAPDH (36.4%). Anti-aldolase was associated with male gender (P = 0.012, OR 7.11, 95% CI 1.54-32.91). Anti-CAII showed significant association with age of onset (P = 0.025, 95% CI - 17.28 to - 1.24), while anti-α-enolase (P = 0.002, OR 4.37, 95% CI 1.83-10.37) and anti-GAPDH (P = 0.001, OR 1.87, 95% CI 1.32-2.64) were significantly associated with nonrecordable electroretinography. Association between the antibody profiles and clinical outcomes may be used to direct and adjust the treatment plans and provide insights in the pathogenesis of AIR.

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.

The preservation method and timing on accuracy of manual leukocytes counts in synovial fluid.

OBJECTIVES: To compare the efficacy of heparin and EDTA and determine the impact of time delays in stabilizing leukocyte counts in synovial fluid. MATERIAL AND METHOD: 33 specimens were collected in heparin-preserved and EDTA-preserved containers. Total cell count was performed manually at 1 hour and 24 hours. Correlation between cell counts from both preservatives and the leukocyte number at 1 hour and 24 hours were analyzed by means of agreement measurement. RESULTS: There were good correlations between the leukocyte numbers from the specimens preserved by heparin and EDTA (ICC = 0.889, r = 0.879, P < 0.0001 at 1 hour and ICC = 0.822, r = 0.693, p < 0.0001 at 24 hour). At 24 hours, total cell counts from EDTA-preserved samples were comparable to those obtained at 1 hour (ICC = 0.985, r = 0. 986, p < 0. 0001) and were not different from those of the heparinized samples (ICC = 0.833, r = 0. 751, p < 0.0001) but the ICC value was higher. CONCLUSION: EDTA was as effective as heparin for preservation of synovial fluid. Therefore, it can be used routinely as a preservative of synovial fluid.

Metabolic syndrome is associated with disease activity in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association between metabolic syndrome (MS) and disease activity in patients with rheumatoid arthritis (RA). METHODS: Siriraj Rheumatoid Arthritis registry is a prospective cohort study establishing since May 2011. A total of 267 patients who had complete data in February 2015 were included in these analyses. All clinical and laboratory data related to disease activity, functional status, and parameters of MS according to the 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) were collected. Univariate and backward stepwise multivariate analyses were performed to identify factors associated with MS. RESULTS: Most (88%) were female with the mean age±standard deviation of 59±11.1 years old. MS was found in 43 patients (16%). Patients with MS had a significantly lower proportion of patients with remission (time-adjusted mean of disease activity score 28 or DAS28<2.6) than those with non-MS (2.3% vs. 16.5%, P=0.02). Multiple logistic regression analysis identified 3 independent factors associated with MS including body mass index [OR 1.2, 95% CI 1.1 to 1.3], educational level≤12 years [OR 5.92, 95% CI 1.47 to 23.83], and disease remission [OR 0.11, 95% CI 0.01 to 0.93]. This model correctly predicted 84% of cases. CONCLUSION: Remission rate is significantly lower in RA patients with MS. Disease activity of RA, body mass index, and educational level are associated with metabolic syndrome in patients with RA.

Prevalence and risk factors for chloroquine maculopathy and role of plasma chloroquine and desethylchloroquine concentrations in predicting chloroquine maculopathy.

AIM: To determine the prevalence and to identify the risk factors of chloroquine maculopathy (CM), and to evaluate the association of plasma chloroquine (CQ) and desethylchloroquine (DCQ) levels and CM. METHODS: Rheumatoid arthritis (RA) patients who had taken CQ for at least 6 months and stable CQ dosage for at least 2 months were included. CM was diagnosed by dilated ocular examination and automated visual field. Plasma CQ and DCQ levels were determined by liquid chromatography tandem mass spectrometry method. Logistic regression was used to explore risk factors associated with CM. RESULTS: One hundred and ninety-three patients were included with median CQ duration (range) of 50.2 months (6.0-269.8) and cumulative dose of 137.4 g (16.4-1226.5). The prevalence of CM was 13.5%. Factors associated with CM identified from univariate analysis were age > 60 years, and creatinine clearance with odds ratio (OR) (95%CI) of 5.79 (2.42, 13.84), and 0.98 (0.96, 1.00). In multivariate analysis, older age, usage > 5 years, and current dose from 2.5 mg/kg ideal body weight [IBW]/day were the factors significantly associated with CM with OR of 5.89 (2.38, 14.57), 2.94 (1.10, 7.83), and 3.32 (1.04, 10.60), respectively, while plasma CQ and DCQ showed no association with CM. CONCLUSIONS: The prevalence of CM was 13.5% among RA patients taking CQ for at least 6 months. Age > 60 years, duration of CQ usage > 5 years and current CQ dose ≥2.5 mg/kg IBW/day were the risk factors for CM. The plasma CQ or DCQ levels demonstrated no correlation in developing CM.

A newly recognized polyosteolysis/hyperostosis syndrome.

We report a newly recognized bone disorder consisting of polyostotic expansile osteolysis affecting long bones and iliac bones; hyperostosis of the skull, thoracic cage, and medial portion of both clavicles; pectus carinatum; gigantiform synovial masses of the elbows and knees; atrial septal defect; cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones can be grouped into four general types of skeletal pathology: (1) expansile osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis, and (4) hyperostosis. Some bones remained unaffected. We have named the condition "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any previously reported bone disorder, including familial expansile osteolysis, juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous dysplasia). Because our patient shared some features in common with juvenile Paget disease, we thought that mutational analysis of TNFRSF11B was indicated, even though our patient had some manifestations not found in juvenile Paget disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the parents of our propositus were first cousins suggests that polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive inheritance.