Seasonal vitamin D levels and lupus low disease activity state in systemic lupus erythematosus.

BACKGROUND: Seasonal variation and sunlight exposure can impact serum vitamin D levels, potentially influencing lupus symptoms. We investigated seasonal vitamin D levels and their correlation with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). METHODS: Serum 25(OH) vitamin D3 (25(OH)D3) levels were categorised as deficient (25(OH)D3 < 10 ng/mL), insufficient (10-30 ng/mL) and sufficiency (>30 ng/mL) in participants analysed in winter (n = 407) and summer (n = 377). Logistic regression analysis was performed to assess the impact of vitamin D levels on achieving a lupus low disease activity state (LLDAS), stratified by season. RESULTS: The mean serum 25(OH)D3 levels differed significantly between the winter and summer measurement groups (22.4 vs. 24.2 ng/mL; p = .018). The prevalences of vitamin D deficiency, insufficiency and sufficiency in the winter group were 12.8%, 66.6% and 20.6%, respectively, compared with 4.5%, 67.9% and 27.6% in the summer group. Achieving LLDAS was highest in the vitamin D sufficiency group (winter: 56.6%, summer: 55%) and lowest in the vitamin D deficiency group (winter: 15.4%, summer: 13.6%), with significant differences (all p < .001). Multivariate analysis identified SLE disease activity index ≤4, normal anti-double-stranded DNA and vitamin D sufficiency as significant factors for achieving LLDAS in both seasons. CONCLUSIONS: Sufficient vitamin D levels are important for achieving LLDAS in patients with SLE during winter and summer. Therefore, physicians should pay attention to the adequacy of vitamin D levels and consider recommending vitamin D supplementation for patients with vitamin D insufficiency.

Uncovering risk factors for adverse events and infections in rheumatoid arthritis and rheumatoid arthritis with interstitial lung disease under treatment with biologics or targeted synthetic DMARDs: insights from the KOBIO Registry.

OBJECTIVES: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry. METHODS: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD. RESULTS: Among all patients with RA, 45.7% withdrew b/tsDMARDs, whereas among those with RA-ILD, a higher proportion of 57.4% withdrew their treatment regimen. The main reason for withdrawing b/tsDMARDs in the RA-ILD group was AEs, with infections accounting for the largest proportion of reported AEs. In multivariable analysis of the risk factors for overall AEs and infections in the RA-ILD group, older age was identified as a risk factor for overall AEs (odds ratio [OR], 3.01; p=0.014), and only a current smoking status was identified as a risk factor for infections (OR, 2.11; p=0.035). CONCLUSIONS: Patients with RA-ILD exhibited a higher rate of b/tsDMARDs withdrawal due to overall AEs and infections than those with RA without ILD. In the RA-ILD group, older age was identified as a risk factor for overall AEs, whereas a current smoking status was identified as a risk factor for infections.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

PURPOSE: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. METHODS: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. RESULTS: Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. CONCLUSION: Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.

Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation.

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.

Efficacy and drug retention of tofacitinib in rheumatoid arthritis: from the nationwide Korean College of Rheumatology Biologics registry.

OBJECTIVES: Janus kinase inhibitors are expected to change the management patterns and prognosis of chronic rheumatic diseases. This study aimed to evaluate the efficacy, drug retention, and adverse events of tofacitinib, a Janus kinase inhibitor, for rheumatoid arthritis (RA) using a Korean nationwide database. METHODS: Data of patients with RA receiving tofacitinib were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry, including clinical characteristics and disease activity markers for RA. Outcomes of clinical efficacy, drug survival rate, and safety profiles were compared between biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and -failure patients. Mann-Whitney U-test, logistic regression analysis, Kaplan-Meier analysis, and log-rank test were used in data analysis. RESULTS: Three hundred patients with RA received tofacitinib therapy (16.3% male; mean age 55.4±11.9 years); 91 patients were bDMARD-naive. Baseline disease activity markers and proportions of patients who were taking conventional synthetic DMARDs were not different between bDMARD-naive and bDMARD-failure patients. American College of Rheumatology responses and disease activity score-28 did not differ between bDMARD-failure and -naive patients at the 1-year follow-up. The drug retention rate of tofacitinib did not differ between bDMARD-failure (155 per 2.4 years) and -naive patients (89 per 1.9 years) (log-rank test, p=0.202). In logistic regression, the positivity of RF and ACPA were associated with reduced drug retention (p=0.01 and 0.02, respectively). Totally 83 (27.7%) of patients had adverse, and 14 (4.7%) patients had herpes zoster infection. CONCLUSIONS: Nationwide real-world data showed that tofacitinib therapy is effective in patients with RA independent of previous use of a bDMARD. The drug retention of tofacitinib did not differ between bDMARD-failure and -naive patients, and RF or ACPA positivity may be associated with reduced discontinuation of tofacitinib.

A link between CD8+CD27-CD28- T cells expressing chemerin chemokine-like receptor 1 and rheumatoid arthritis.

OBJECTIVES: Transcription of the chemerin chemokine-like receptor 1 (CMKLR1) has been observed in T cell subsets, but its role in T cells has not been well studied. As previously reported, the levels of its ligand, chemerin, are increased in the plasma and synovial fluid of patients with rheumatoid arthritis (RA); hence, we aimed to explore the expression and role of CMKLR1 in the T cells of these patients. METHODS: Peripheral blood and synovial fluid from patients with RA or osteoarthritis and healthy individuals were collected to analyse the frequency of CD27-CD28- T cells and the expression of CMKLR1 and TNF-α by flow cytometry. Chemotaxis of T cells was assessed using a Transwell migration assay. Chemerin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: CMKLR1 was preferentially expressed in CD27-CD28- T cell subsets. Its surface levels were reduced by stimulation with anti-CD3 antibody or chemerin. We found a correlation between CMKLR1+CD8+CD27-CD28- T cell frequency and disease activity score 28 of RA. Chemerin treatment up-regulated but CMKLR1 inhibitor treatment down-regulated TNF-α expression in CD8+CD27-CD28- T cells, half of which express CMKLR1 on average. Moreover, chemerin induced migration of these cells. Analysis of blood and synovial fluid samples of RA showed a reduction of CMKLR1+CD27-CD28- T cell levels in the synovial fluid, with a few exceptions. CONCLUSIONS: Our results suggest that CMKLR1 expression in T cells may be involved in RA pathogenesis through modulation of TNF-α expression and cell migration.

Effects of COVID-19 and Influenza Vaccination on Rheumatic Diseases: Results From a Survey of Patient-Reported Outcomes After Vaccination.

BACKGROUND: This study aimed to compare the occurrence of adverse events (AEs) and disease flares after vaccination against coronavirus disease 2019 (COVID-19) and influenza in patients with autoimmune rheumatic diseases (ARDs). METHODS: Between November 2021 and March 2022, a survey was conducted among patients with ARD who received COVID-19 and influenza vaccinations. The questionnaire included 11 mandatory and closed-ended questions, and the following items were collected: medical history, immunization history, type of vaccine, patient-reported AEs, flare-up of the underlying disease after vaccination, and a confirmed diagnosis of COVID-19 or influenza. We compared the occurrence of vaccine-related adverse reactions to the COVID-19 and influenza vaccines based on the survey results. Multivariate logistic regression analysis was used to identify the factors affecting AEs or disease flares and to compare the post-vaccine response to mixed and matched vaccines. RESULTS: We analyzed 601 adults with ARD who received the COVID-19 vaccine, with a mean age of 49.6 years (80.5% female). A total of 255 participants (42.4%) received a complete course of primary vaccination, 342 (56.9%) completed the booster dose, and 132 (38.6%) received a mixed vaccine. The frequencies of AEs (188 [52.2%] vs. 21 [5.8%]; P < 0.001) and disease flares (58 [16.2%] vs. 5 [1.4%]; P < 0.001) after COVID-19 vaccination were significantly higher than those after influenza vaccination. In the risk factor analysis, previous allergic reaction to other vaccines (odds ratio, 1.95; confidence interval, 1.07-3.70; P = 0.034) was the only factor associated with the occurrence of AEs. There was no difference in the post-vaccine responses between the mixed and matched vaccines. CONCLUSION: The results of the survey of patients with ARD revealed that patient-reported AEs and underlying disease flares after receiving the COVID-19 vaccine were significantly higher than those after the influenza vaccine.

Increased Immunoglobulin Gamma-3 Chain C in the Serum, Saliva, and Urine of Patients with Systemic Lupus Erythematosus.

Immunoglobulin gamma-3 chain C (IGHG3) levels have been detected in the blood and tissue of patients with systemic lupus erythematosus (SLE). This study aims to assess its clinical value by measuring and comparing levels of IGHG3 in different body fluids in patients with SLE. The levels of IGHG3 in saliva, serum, and urine from 181 patients with SLE and 99 healthy controls were measured and analyzed. In patients with SLE and healthy controls, salivary IGHG3 levels were 3078.9 ± 2473.8 and 1413.6 ± 1075.3 ng/mL, serum IGHG3 levels were 478.1 ± 160.9 and 364.4 ± 97.9 µg/mL, and urine IGHG3 levels were 64.0 ± 74.5 and 27.1 ± 16.2 ng/mL, respectively (all p < 0.001). Salivary IGHG3 was correlated with ESR (correlation coefficient [r], 0.173; p = 0.024). Serum IGHG3 was correlated with leukocyte count (r, -0.219; p = 0.003), lymphocyte count (r, 0.22; p = 0.03), anti-dsDNA antibody positivity (r, 0.22; p = 0.003), and C3 levels (r, -0.23; p = 0.002). Urinary IGHG3 was correlated with hemoglobin level (r, -0.183; p = 0.021), ESR (r, 0.204; p = 0.01), anti-dsDNA antibody positivity (r, 0.262; p = 0.001), C3 levels (r, -0.202; p = 0.011), and SLE disease activity index (r, 0.332; p = 0.01). Urinary IGHG3 was higher in patients with nephritis than in those without (119.5 ± 110.0 vs. 49.8 ± 54.4 ng/mL; p < 0.01). IGHG3 was increased in the saliva, serum, and urine of patients with SLE. While salivary IGHG3 was not identified to be specific to SLE disease activity, serum IGHG3 showed correlations with clinical characteristics. Urinary IGHG3 levels were associated with disease activity and renal involvement in SLE.

Association between nuclear factor of activated T cells C2 polymorphisms and treatment response in rheumatoid arthritis patients receiving tumor necrosis factor-alpha inhibitors.

OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.

Clinical Characteristics of Patients With Psoriatic Spondylitis Versus Those With Ankylosing Spondylitis: Features at Baseline Before Biologic Therapy.

BACKGROUND: Clinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement. METHODS: In this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent. Data from 2,221 patients with ankylosing spondylitis (AS) registered during the same period were also analyzed. We divided patients with PsA into patients with or without axial involvement and then added AS patients with psoriasis (total three subgroups) for comparative analyses. RESULTS: Asymmetric oligoarthritis was the most common clinical manifestation in patients with PsA, followed by symmetric polyarthritis and spondylitis. Our analysis indicated that methotrexate and sulfasalazine were the two most prescribed disease-modifying antirheumatic drugs for patients with PsA before starting biologic therapy. The patients with psoriatic spondylitis had more peripheral joint involvement (P = 0.016), less prior uveitis (P < 0.001), and lower human leukocyte antigen B27 (HLA-B27) positivity (P < 0.001) than the AS patients with psoriasis. Furthermore, syndesmophytes and radiographic sacroiliitis were prevalent among patients with PsA and AS patients with psoriasis who had the HLA-B27 gene. CONCLUSION: Our study shows that the degree of peripheral arthritis is less severe in Korean patients with PsA who require biologics and reestablishes that psoriatic spondylitis is a common and important clinical pattern in Korean patients with PsA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965132.

Effectiveness and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis: real-world data from the KOBIO Registry.

OBJECTIVES: We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). METHODS: Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). RESULTS: Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. CONCLUSIONS: Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.

Salivary Biomarkers in Patients with Sjögren's Syndrome-A Systematic Review.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary ß2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated.

An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease.

Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET formation stimulate autoimmune responses related to a wide range of inflammatory autoimmune diseases by exposing autoantigens in susceptible individuals. The association between increased NET formation and autoimmunity was first reported in antineutrophil cytoplasmic antibody-related vasculitis, and the role of NETs in various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, has since been elucidated in research. Herein, we discuss the mechanistic role of neutrophils, including NETs, in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), and provide their clinical values as biomarkers for monitoring and prognosis.

Salivary Immunoglobulin Gamma-3 Chain C Is a Promising Noninvasive Biomarker for Systemic Lupus Erythematosus.

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively; p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively; p < 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.

Preclinical rheumatoid arthritis and rheumatoid arthritis prevention.

PURPOSE OF REVIEW: This review is to provide an update on the current understanding of rheumatoid arthritis (RA) development related to disease development prior to the onset clinically apparent synovitis (i.e. Pre-RA), and opportunities for disease prevention. RECENT FINDINGS: A growing number of studies have demonstrated that serum elevations of autoantibodies rheumatoid factor, antibodies to citrullinated protein/peptide antigens (ACPAs) and antibodies to other posttranslationally modified proteins (e.g. carbamylated proteins) are highly predictive of future development of inflammatory arthritis/RA during a period that can be termed Pre-RA. Other factors including genetic, environmental, symptoms and imaging findings can also enhance prediction. Moreover, several novel biomarkers and changes in autoantibodies (e.g. glycosylation of variable domains) have been identified in Pre-RA. There has also been growing evidence that initiation and propagation of RA-related autoimmunity during the Pre-RA phase may be related to mucosal processes. The discovery of Pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent IA in at-risk individuals. Additional studies are evaluating the ability of drugs including abatacept, hydroxychloroquine and methotrexate to prevent or delay future RA. SUMMARY: The results from ongoing natural history and prevention trials in RA should further inform several critical issues in RA prevention including identification and enrolment of individuals at high-risk of imminent RA, the efficacy, safety and cost-effectiveness of prevention, and potentially the identification of new targets for prevention.

Retention rate and long-term safety of biosimilar CT-P13 in patients with ankylosing spondylitis: data from the Korean College of Rheumatology Biologics registry.

OBJECTIVES: To evaluate the long-term drug retention, efficacy, and safety of the infliximab biosimilar CT-P13 in Korean patients with ankylosing spondylitis (AS) in clinical practice. The primary outcome was drug retention (i.e. time to treatment discontinuation or changing to another biologic) in Korean patients with AS. Additional outcomes included efficacy and safety. METHODS: Data were collected through the Korean College of Rheumatology Biologics (KOBIO) registry (ClinicalTrials.gov identifier: NCT01965132). CT-P13 efficacy was assessed using standard disease activity parameters, and safety was evaluated by adverse events (AEs). RESULTS: Between December 2012 and December 2017, 244 patients with AS treated with CT-P13 were enrolled. Of those, 203 (83.2%) received CT-P13 as first-line therapy. The median duration of treatment was 2.05 years. After 4 years' follow-up, the retention rate of CT-P13 in the overall patient population was 66%. Treatment changes or discontinuations occurred in 38 (15.6%) and 32 (13.1%) patients, respectively. Lack of efficacy was the most common reason for treatment changes, whereas AEs were the most common single cause of discontinuation. Disease activity decreased markedly from baseline following initiation of CT-P13 treatment, and thereafter remained stable. A total of 313 AEs occurred in 118 patients (48.4%); the majority (94.6%) were mild or moderate in severity. The most common treatment-related AEs were infusion or injection-site reactions (4.1% of patients), uveitis (3.7%), and skin rash (3.7%). CONCLUSIONS: In this real-world study, CT-P13 demonstrated encouraging drug retention rates and times, together with reasonable long-term efficacy and safety, in Korean patients with AS.

Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in Patients With Polymyalgia Rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls. METHODS: Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents. RESULTS: The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p < 0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p < 0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p < 0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p < 0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043). CONCLUSION: TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.

Tocilizumab-induced anaphylaxis in patients with adult-onset Still's disease and systemic juvenile idiopathic arthritis: a case-based review.

The benefits afforded by tocilizumab (TCZ) in patients with adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) have been described in previous studies. However, few reports have evaluated severe hypersensitivity reactions (HSRs) to TCZ in patients with AOSD or SJIA. We describe three instances of TCZ-induced anaphylactic reactions in AOSD/SJIA patients, and review relevant prior reports on patients with various rheumatic diseases. Two of our cases exhibited shock and cardiovascular collapse; TCZ was discontinued in all three cases. All events occurred within 20 min of TCZ infusion, after at least three prior infusions, indicating an IgE-mediated mechanism and previous sensitization to TCZ. In all three cases, mild HSRs had been observed about 1 month before the anaphylactic events, but pre-medication with antihistamines and corticosteroids failed to prevent anaphylaxis. All three cases had active AOSD or SJIA disease, and were refractory to other immunosuppressive agents. It is essential to be aware that severe anaphylaxis to TCZ can develop in patients with active refractory AOSD or SJIA, and to be cautious when medicating certain patients. Anaphylaxis is a serious condition that can be fatal; TCZ infusion should not be re-challenged via pre-medication in patients who exhibited mild HSRs before TCZ without desensitization.

Seasonal Variations and Associated Factors of Gout Attacks: a Prospective Multicenter Study in Korea.

BACKGROUND: We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. METHODS: We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. RESULTS: Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; -0.9%, fall; -1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. CONCLUSION: In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

The levels of CXCL12 and its receptor, CXCR4, as a biomarker of disease activity and cutaneous manifestation in adult-onset Still's disease.

OBJECTIVES: This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD). METHODS: Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry. RESULTS: The serum CXCL12 levels in patients with AOSD (2,452±1,531 pg/mL) were higher than those in HC (1,708±1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449±16,627 pg/mL) were higher than those in HC (3,046±2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4±27.5% and that of CXCL12-positive inflammatory cells was 16.7±13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin. CONCLUSIONS: These results provide that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.