The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

OBJECTIVE: Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for >6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged ≤65 and >65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1~3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. RESULTS: Overall, 121 patients were analysed. Mean±standard deviation tacrolimus dose baseline-Week 24 was 1.81±0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5±0.8 (baseline) to 3.7±1.5 (Week 24; p < 0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was −0.06±0.38 (p=0.1550) and −0.04±0.28 (p=0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. CONCLUSION: Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA.
Antirheumatic Agents* ; Arthritis, Rheumatoid* ; Blood Sedimentation ; Bone Density ; Classification ; Densitometry ; Femur ; Humans ; Joints ; Korea ; Mass Screening ; Osteoporosis ; Rheumatology ; Tacrolimus*

OBJECTIVES: The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. METHODS: Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin–clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. RESULTS: The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin–clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin–clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. CONCLUSION: Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis.
Animals ; Arthritis ; Arthritis, Experimental* ; Aspirin ; Female ; Humans ; Rats

Behcet's disease (BD) is a multi-systemic inflammatory disease of unknown origin that affects nearly all organs including the nervous system. Although the neurological involvement is less frequent than other major presentations, it is important because it can produce severe disabilities. Peripheral nervous system manifestations are relatively rare in BD. Although few cases of peripheral neuropathy or myopathy have been reported in BD, they are cases of multiple neuropathies, sensorimotor peripheral neuropathy, or neuropathy autonomic dysfunction. Guillain-Barre syndrome (GBS), also known as an acute inflammatory demyelinating polyneuropathy, is an acute demyelinating polyradiculopathy of uncertain etiology. No case of GBS associated with BD in Korea has been reported. Herein we report on a patient of BD who suffered from weakness of extremities and was diagnosed as GBS.
Extremities ; Guillain-Barre Syndrome* ; Humans ; Korea ; Muscular Diseases ; Nervous System ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Polyradiculopathy

This article has been retracted.

Systemic lupus erythematosus (SLE) is an autoimmune disorder affected by multiple genetic, hormonal and environmental factors, which makes it impossible to identify the exact cause of this ailment by only investigating SLE patients, who are genetically heterogeneous, and live in various environments. Therefore, the study of mouse models of lupus has provided valuable clues to help identify, and to validate, novel molecular pathways and targets implicated in the pathogenesis of the disease. While there is no perfect model to reflect all the disease phenotypes observed in human patients, disease subsets are represented in various animal models, which allows modulation of a particular pathophysiological pathway, resulting in the possibility of dissecting its specific contribution to disease development. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci, from which several candidate genes have been found, while induced models of lupus have provided insight into the role of environmental factors, as well as a better understanding of the cellular mechanisms by which SLE develops. Animal models also allow us to screen and evaluate potential preventive and therapeutic agents. Correlation of specific pathways in animal models to subsets of human disease offers the unique possibility of more accurate preclinical predictions of efficacy for single or combinatorial therapeutic approaches in the clinic. Here, we introduce various animal models of SLE, and review current data focused on genetic factors that are associated with susceptibility or phenotypes of lupus, leading into the present understanding of the genetic basis in lupus pathogenesis.
Animals ; Humans ; Lupus Erythematosus, Systemic ; Mice ; Models, Animal ; Phenotype

BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.
Animals ; Antigens, CD3 ; Arthritis ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Biomarkers ; Collagen Type II ; Down-Regulation ; Gene Expression ; Genes, T-Cell Receptor ; Immunization ; Joints ; Models, Animal ; Oligonucleotide Array Sequence Analysis ; Rats ; Receptors, Antigen, T-Cell ; Synovial Membrane ; T-Lymphocytes ; Thymus Gland ; Transcriptome

BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.
Animals ; Antigens, CD3 ; Arthritis ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Biomarkers ; Collagen Type II ; Down-Regulation ; Gene Expression ; Genes, T-Cell Receptor ; Immunization ; Joints ; Models, Animal ; Oligonucleotide Array Sequence Analysis ; Rats ; Receptors, Antigen, T-Cell ; Synovial Membrane ; T-Lymphocytes ; Thymus Gland ; Transcriptome

Infliximab is a chimeric mouse/human monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha) that is used worldwide to treat rheumatic disease. However, the reactivation of tuberculosis, including extrapulmonary menifestation, is a severe side effect of anti-TNF-alpha treatment. Mycobacterium tubercluosis causes two forms of joint involvement, TB arthritis and Poncet's disease. Poncet's disease is a rare aseptic form of arthritis, known as reactive arthritis in tuberculosis. We encountered a case of tuberculous peritonitis with Poncet's disease in a 38-yearold man with a history of ankylosing spondylitis that was treated with infliximab. We report this case with a review of the literature.
Antibodies, Monoclonal ; Arthritis ; Arthritis, Reactive ; Humans ; Joints ; Mycobacterium ; Peritonitis, Tuberculous ; Rheumatic Diseases ; Spondylitis, Ankylosing ; Tuberculosis ; Tumor Necrosis Factor-alpha ; Infliximab

Leflunomide is a disease-modifying antirheumatic drug that has been available in Korea since 2003. Leflunomide induced interstitial pneumonitis has been reported as an adverse effect in other countries but not in Korea. A 57-year-old woman was treated with leflunomide since she had been resistant to methotrexate, hydroxychloroquine and sulfasalazine. She developed high fever, dyspnea, and non-productive cough 3 months after the administration of leflunomide. She was diagnosed leflunomide-induced interstitial pneumonitis based on history, physical, laboratory, radiologic and pathologic findings. The patient was treated by prednisolone 1 mg/kg/day with cholestyramine 24 g/day, resulting in dramatic improvement. Here we report a case of leflunomide induced pneumonitis treated successfully with high dose steroid.
Arthritis, Rheumatoid ; Cholestyramine Resin ; Cough ; Dyspnea ; Female ; Fever ; Humans ; Hydroxychloroquine ; Korea ; Lung Diseases, Interstitial* ; Methotrexate ; Middle Aged ; Pneumonia ; Prednisolone ; Sulfasalazine