Effectiveness and safety of adalimumab in patients with intestinal Behçet's disease: a real-world prospective observational study in South Korea.

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

High Baseline Neutrophil-to-Lymphocyte Ratio Could Serve as a Biomarker for Tumor Necrosis Factor-Alpha Blockers and Their Discontinuation in Patients with Ankylosing Spondylitis.

BACKGROUND: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). METHODS: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. RESULTS: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). CONCLUSIONS: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia.

BACKGROUND: The present study aimed to evaluate microbial diversity, taxonomic profiles, and fecal short chain fatty acid (SCFA) in female patients with fibromyalgia syndrome (FMS). METHODS: Forty participants (19 patients with FMS and 21 controls) were included in the study, and the diagnosis of FMS was made based on the revised American College of Rheumatology criteria. DNA extraction from fecal samples and 16S rRNA gene sequencing were conducted to estimate microbial composition. To compare alpha diversity, the Shannon index accounting for both evenness and richness, Pielou's evenness, and Faith's phylogenetic diversity (PD) were calculated. Unweighted and weighted UniFrac distances, Jaccard distance, and Bray-Curtis dissimilarity were used to calculate beta diversity. Furthermore, stool metabolites were analyzed using gas chromatography-mass spectrometry, and a generalized regression model was used to compare the SCFA of stools between FMS and healthy controls. RESULTS: Compared with the control, patients with FMS had lower observed OTU (p = 0.048), Shannon's index (p = 0.044), and evenness (p < 0.001). Although patients with FMS had a lower PD than did controls, statistical significance was not reached. We observed significant differences in unweighted (p = 0.007), weighted UniFrac-based diversity (p < 0.005), Jaccard distance (p < 0.001), and Bray-Curtis dissimilarity (p < 0.001) between the two groups. Although the FMS groups showed lower propionate levels compared with those of the control group, only marginal significance was observed (0.82 [0.051] mg/g in FMS vs. 1.16 [0.077] mg/g in the control group, p = 0.069). CONCLUSIONS: The diversity of the microbiome in the FMS group was lower than that in the control group, and the reduced stool propionate levels could be associated with the decreased abundance of propionate-producing bacteria.

Carotid Arterial Stiffness and Cardiometabolic Profiles in Women with Fibromyalgia.

BACKGROUND: The present study aimed to evaluate the association between FM and cardiometabolic risk factors and carotid arterial stiffness in FM patients. METHODS: The cardiometabolic risk profile was defined based on the Adult Treatment Panel III panel. Carotid intimal media thickness (cIMT) and arterial stiffness were assessed using high-resolution ultrasonography. Multivariate logistic analysis was performed to estimate the association between FM and cardiometabolic risk factors. We used a general linear regression to compare the cIMT and carotid beta-index between the participants with and without FM. Pearson's coefficient was calculated to evaluate the potential correlation between cardiometabolic risk profiles, cIMT, and arterial stiffening in FM. RESULTS: FM participants showed a higher risk of central obesity (odds ratio [OR] = 3.21, 95% confidence interval [CI] 1.49, 6.91), high triglyceride (OR = 4.73, 95% CI 2.29, 9.79), and impaired fasting glucose (IFG) (OR = 4.27, 95% CI 2.07, 8.81) compared to the control group. The FM group exhibited higher beta-index values than the control group (p = 0.003). Although IFG and triglyceride glucose index showed a tendency to correlate with the beta-index, statistical significance was not observed. CONCLUSIONS: FM was associated with an increased risk of central obesity, high triglyceride levels, and IFG. Furthermore, advanced arterial stiffness of the carotid artery was observed in FM, which might be correlated with insulin resistance.

Comparison of persistence rates between allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout: an 8-year retrospective cohort study.

INTRODUCTION/OBJECTIVES: Lifelong urate-lowering therapy (ULT) with xanthine oxidase inhibitors (XOIs), such as allopurinol and febuxostat, is the cornerstone of gout treatment. This study aimed to compare drug persistence between allopurinol and febuxostat as first-line ULT in patients with gout in real practice. METHOD: In this retrospective cohort study, we evaluated 602 patients with gout in whom allopurinol or febuxostat was newly initiated from December 2011 to November 2018 at a tertiary rheumatology centre. Persistence was defined as the duration from the first description date to the end of treatment with XOIs or the end of the study period (November 2019). RESULTS: Among the 602 gout patients, the mean age was 60.2 years and 234 (38.9%) patients had tophi. Allopurinol and febuxostat were started in 237 (39.3%) and 365 (60.6%) patients, respectively. During the study period, 282 (46.8%) patients stopped taking XOIs, and the most common reason for XOI withdrawal was poor health literacy (61.3%). The 1- and 5-year persistence rates of XOIs were 67.2% and 40.9%, respectively. In the Kaplan-Meier analysis, persistence rates of allopurinol were significantly lower than those of febuxostat (p < 0.001). In the multivariable Cox regression model, allopurinol use was a significant risk factor for discontinuation of XOIs (HR = 2.01, p < 0.001). In addition, the presence of tophi and symptom duration < 24 months was independently associated with a higher risk of XOI withdrawal. CONCLUSIONS: Long-term persistence of XOIs was suboptimal, and allopurinol had worse persistence rates than febuxostat among patients with gout. Key Points • Long-term persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) among patients with gout was suboptimal, and the major reason for XOI discontinuation was poor health literacy in our study. • We demonstrated that allopurinol had worse persistence rates than febuxostat among patients with gout, suggesting that febuxostat is a better option for long-term ULT in light of medication adherence in a real-world setting. • Patients with gout with tophi and shorter symptom duration were found to be at high risk for poor persistence of XOIs.

Clinical characteristics and survival of 413 patients with systemic lupus erythematosus in southeastern areas of South Korea: A multicenter retrospective cohort study.

AIMS: To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. METHODS: We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. RESULTS: Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83 months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR] = 7.19, P = .001), pleuritis and/or pericarditis (HR = 3.28, P = .012), childhood-onset (HR = 3.57, P = .012), and late-onset (HR = 4.65, P = .011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. CONCLUSION: This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

BACKGROUND: To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). METHODS: This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. RESULTS: A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). CONCLUSIONS: Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as predictors of 12-week treatment response and drug persistence of anti-tumor necrosis factor-α agents in patients with rheumatoid arthritis: a retrospective chart review analysis.

Data are scarce regarding the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with treatment response and persistence of anti-TNF-α agents in patients with rheumatoid arthritis (RA). Thus, we investigated whether baseline NLR and PLR could predict 12-week treatment response and long-term persistence of anti-TNF-α agents in RA patients. This is a retrospective chart review analysis of 82 women with RA who started anti-TNF-α agents as the first-line biologic therapy and 328 healthy age-matched women. RA patients were divided into high and low baseline NLR or PLR subgroups using the median split. European League against Rheumatism (EULAR) treatment response was evaluated at 12 weeks. RA patients had significantly higher NLR and PLR than controls. High baseline NLR and PLR groups showed higher 12-week EULAR non-response rate than low NLR (30% vs 7.1%, p = 0.01) and PLR groups (27.5% vs 9.5%, p = 0.047), respectively. After adjusting for confounding factors, high baseline NLR (OR 5.57, p = 0.014) and PLR (OR 4.24, p = 0.04) were significantly associated with a higher risk of EULAR non-response at 12 weeks. During the study period, 47 (57.3%) RA patients (lack of efficacy: n = 31; adverse events: n = 16) discontinued anti-TNF-α agents. High baseline NLR was associated with an increased risk of anti-TNF-α agent withdrawal due to lack of efficacy (HR 2.12, p = 0.045). Our data suggest that baseline NLR and PLR are useful markers for predicting the treatment outcome of anti-TNF-α agents in RA patients.

Evaluation of an Automated Screening Assay, Compared to Indirect Immunofluorescence, an Extractable Nuclear Antigen Assay, and a Line Immunoassay in a Large Cohort of Asian Patients with Antinuclear Antibody-Associated Rheumatoid Diseases: A Multicenter Retrospective Study.

We assessed the diagnostic utility of the connective tissue disease (CTD) screen as an automated screening test, in comparison with the indirect immunofluorescence (IIF), EliA extractable nuclear antigen (ENA), and line immunoassay (LIA) for patients with antinuclear antibody- (ANA-) associated rheumatoid disease (AARD). A total of 1115 serum samples from two university hospitals were assayed using these four autoantibody-based methods. The AARD group consisted of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), and mixed connective tissue disease (MCTD). The qualitative results of all four autoantibody assays showed a significant association with AARDs, compared to controls (P < 0.0001 for all). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for differentiating total AARDs, SLE, SSc, SS, and MCTD from controls were 0.89, 0.93, 0.73, 0.93, and 0.95, respectively. The ROC-AUCs of combination testing with LIA were slightly higher in patients with AARDs (0.92) than those of CTD screen alone. Multivariate analysis indicated that all four autoantibody assays could independently predict AARDs. CTD screening alone and in combination with IIF, EliA ENA, and LIA are potentially valuable diagnostic approaches for predicting AARDs. Combining CTD screen with LIA might be effective for AARD patients.

Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample.

Hyperuricemia is not only a risk factor for gout but also an independent determinant of hypertension, diabetes, and chronic kidney diseases. Although the incidence of gout in Korean adults is increasing, epidemiologic studies on hyperuricemia in the general Korean population are limited. Thus, this study aimed at evaluating the prevalence of hyperuricemia and its associated factors among non-institutionalized Korean adults. The present study included 5548 participants (2403 men and 3145 women) aged ≥ 19 years from The Korea National Health and Nutrition Examination Survey. Based on the new 2016 census data, the age-standardized prevalence and mean uric acid level were calculated using the chi-square test and t test, respectively. A multivariate logistic regression analysis was performed to evaluate the risk factors associated with hyperuricemia. The age-standardized prevalence of hyperuricemia and mean uric acid level in the general Korean population was 11.4% (17.0% in men and 5.9% in women) and 5.1 mg/dL (5.83 mg/dL in men and 4.36 mg/dL in women), respectively. The prevalence of hyperuricemia was high in young Korean adults, and a U-shaped association was observed between hyperuricemia and age. While obesity, metabolic syndrome, renal impairment, and low-grade inflammation were positively associated with hyperuricemia in both sexes, alcohol consumption, education, and current smoking status had a positive association with hyperuricemia only in women. Hyperuricemia is prevalent in the young population in Korea, and special efforts are necessary to reduce the potential harmful effects of hyperuricemia on the health of adults, particularly the younger-generation adults, in Korea.