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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.

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.

Objective: We undertook a 2-part, phase I, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab, a human anti-interleukin-6 monoclonal antibody, in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE)., Methods: In part A, patients with histologically confirmed CLE were randomized to 4 infusions of placebo or 1, 4, or 10 mg/kg sirukumab every 2 weeks. In part B, SLE patients diagnosed according to American College of Rheumatology criteria with a score of 5-12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index were randomized to 4 infusions of placebo or 10 mg/kg sirukumab every 2 weeks., Results: We treated 31 CLE patients (23 with sirukumab, 8 with placebo) and 15 SLE patients (10 with sirukumab, 5 with placebo). Adverse events (AEs) occurred more often with sirukumab than placebo in CLE patients (91% versus 63%) and in SLE patients (90% versus 80%). Sirukumab led to sustained, dose-independent decreases in white blood cell counts, absolute neutrophil counts (neutropenia), and platelet counts (thrombocytopenia) and to minor elevations in total cholesterol levels. The majority of infections were mild respiratory infections. which were reported similarly across CLE cohorts but more often in sirukumab-treated than in placebo-treated SLE patients. Two serious AEs of infection occurred (pneumonia in the 10 mg/kg-treated group and iatrogenic wound infection in the 4 mg/kg-treated group). Sirukumab showed linear pharmacokinetics in CLE patients. Systemic exposure and half-life were comparable between CLE and SLE patients. No patient developed antibodies to sirukumab through 22 weeks. C-reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14., Conclusion: Treatment with intravenous sirukumab infusions was generally well tolerated in both CLE and SLE patients with mild, stable, active disease. Sirukumab demonstrated linear pharmacokinetics over the dose range studied and comparable systemic exposure and half-life in CLE and SLE patients., (Copyright © 2013 by the American College of Rheumatology.)

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., (© 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Proinflammatory cytokines play a role in the pathogenesis of anemia of chronic disease (ACD), which is a common cause of anemia in rheumatoid arthritis (RA). Anemia in RA is associated with increased apoptosis of erythroid cells. However, there is unclear information on the mechanism of ACD in the disease. The purpose of this study is to investigate the role of cytokines on nitric oxide-mediated apoptosis in erythroid progenitor cells of ACD in RA patients. Erythroid progenitor cells from healthy subjects and RA patients with ACD were treated with cytokines like interleukin-1β, tumor necrosis factor-α, and interferon-γ at concentrations of 2, 20, and 40 ng/ml for 14 days. Cell viability and cell apoptosis were analyzed by trypan blue staining and flow cytometry, respectively. The results showed that the highest effect of cytokines on reduction cell viability and induction cell apoptosis was found in 20 ng/ml IFN-γ-treated cells of RA patients. In addition, IFN-γ showed significantly increased nitric oxide production and iNOS mRNA expression, which was measured by Griess assay and real-time PCR, respectively. The percentage of cell apoptosis and NO production was reduced after an inducible nitric oxide synthase inhibitor, SMT, treatment. In conclusion, IFN-γ could induce nitric oxide production-mediated apoptosis process, which might be involved in the pathogenesis of ACD in RA patients.

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.

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.

Background: Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined., Methods: A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up., Results: Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2-76) weeks in albendazole group, 39 (2-74) weeks in single dose ivermectin group, and 26 (2-74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups., Conclusion/significance: This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness., Trial Registration: ClinicalTrials.gov NCT00765024.

Objective: To study of clinical manifestations of osteoarticular tuberculosis., Material and Method: This study is an observational retrospective study design from the electronic medical record database of Siriraj Hospital in 2005-2006., Results: Ninety- nine patients fit in to the inclusion criteria. All were non HIV-infected. There were 44 males (44.4%) and 55 females (55.6%) with a male/female ratio of 8:10. The mean and median age was 50.9 +/- 19.8 and 50 years, respectively, with a range from 1-85 years. The most frequent chief complaint was pain (84.8%), followed by functional disability/neurological deficit (47.5%), constitutional symptoms (38.4%), fever (24.2%), localized swelling (21.2%), fistulas and drainage (11.1%) and discovery as a co-morbid disease (1%). The most frequent clinical manifestation was tuberculous spondylodiscitis (66.7%) followed by tuberculous septic arthritis (28.3%), tuberculous osteomyelitis (10.1%), tuberculous tenosynovitis (4.0%), tuberculous bursitis (2.0%) and tuberculous pyomyositis (2.0%). Concurrent pulmonary TB was 30.3%. The mean and median time to diagnosis was 20.4 +/- 16.9 and 13 weeks, respectively, with a range from 4 days to 104 weeks. The shortest duration of time to diagnosis was 0-4 weeks (19.2%) followed by 12-16 weeks (14.1%) and 20-24 weeks (13.1%). The longest duration of time to diagnosis was 104 weeks (1%). The diagnosis from histopathology was 46.5%, positive AFB 40.4%, positive PCR 33.3% and positive culture 19.2%. The radiological abnormalities were osteolytic lesion (79.8%), narrowing intervertebral disc space/joint space (54.5%), cold abscess (49.5%) and vertebral collapse (43.4%). Surgery with medical treatment was performed on 72.7% while the percentage of those receiving medical treatment only was 27.3%. The results of treatment were improvement with residual deformities/dysfunction occurring in 97%. Death occurred in 3%., Conclusion: Osteoarticular tuberculosis is common in all age groups. Tuberculous spondylodiscitis was the most frequent clinical manifestation in Siriraj Hospital, Thailand. Although the patients were provided with adequate medical and surgical therapy, osteoarticular tuberculosis was still associated with mortality and morbidity.

An epidemiological study of 392 elderly Thai patients with osteoarthritis (OA) of the knee, 86 males and 306 females, with a mean age of 67.8 years, was performed. The prevalence of knee OA was 34.5-45.6 per cent. Most of the patients had completed primary education and had sufficient income. More than half of the patients had pain in both knees, but many of the elderly people used neither knee supports nor walking aids (82.7 and 90.6%). Sixty-four per cent had no previous knowledge concerning the value of exercise. Sixty-five per cent of the patients had never used any pain medication. Three-fourths of the subjects evaluated themselves to have fair to good health. Sixty per cent presented with knee pain when climbing the stairs, and 64.8 per cent had a fair quality of life. Almost all the subjects had mild to moderately severe grade of OA and their X-ray findings were level II-III. The average quadriceps strength and six-minute walking distance were 12.95 +/- 5.51 kilograms and 363.69 +/- 99.34 meters respectively. The five factors that significantly correlated with walking ability were age, sex, the functional incapacity score, using walking aids and level of severity found on X-ray. Previous knowledge about knee exercise did not affect walking ability, but may have been due to the irregularity of the exercise schedule they performed. The elderly should be encouraged to exercise regularly in addition to receive knowledge about proper exercise.

Osteoarthritis (OA) is a common chronic and progressive degenerative joint condition. A major consequence of knee OA is physical disability; especially difficulty with activities requiring ambulation and transfer, which are necessary to maintain independence and a good quality of life. The purposes of this study were to determine the efficacy of a muscle exercise program along with education about knee care, and investigate the clinical factors which influence its therapeutic efficacy. A prospective study was carried out among elderly Thai people aged 60 years and over, living in an urban community of the Bangkok metropolitan area around Siriraj Hospital, between October 1997 and September 1999. The number of elderly people with osteoarthritis of the knee was 392 (male:female=86:306) with a mean age of 67.7+/-6 years. They were interviewed for demographic data and information about their symptoms. The range of the knee movement, quadriceps strength and the six-minute walking distance and a knee X-ray were evaluated. Group exercise was arranged twice a week for 8 weeks for the intervention group only. The results of the study revealed that the quadriceps strength in the intervention group had a tendency to increase and the walking distance was significantly improved especially in the first two months but there was a tendency to decline by the sixth and twelfth month after enrollment. On the other hand, there was no statistically significant difference of both important outcomes for the control group when assessed in the second month. The findings at the sixth and twelfth month after enrollment were that the quadriceps strength was slightly increased but the walking distance was decreased when compared with the initial assessment. An exercise frequency of 12 sessions in two months was sufficient to improve muscle strength and walking distance. Group exercise produces a significant improvement in strength and walking ability, especially in the first two months. Deterioration over time could be due to multiple factors, such as lack of regular exercise, lack of motivation, lack of family support or poor economic status, so we should encourage the elderly to exercise regularly.