Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8–1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892–1.2265) for the maximum plasma concentration and 1.0530 (0.9611–1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations.The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18–4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89–37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

Background and Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods: Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results: Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). Conclusions High IgA levels in patients with KD are prognostic for the risk of CALs.

Background and Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods: Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results: Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). Conclusions High IgA levels in patients with KD are prognostic for the risk of CALs.

BACKGROUND: Lamivudine and abacavir sulfate are widely used nucleoside/tide reverse transcriptase inhibitors (NRTI) backbone agents, which are recommended in major international treatment guidelines. The fixed-dose combination of lamivudine and abacavir sulfate has been developed to contribute to low pill burden of antiretroviral therapy (ART) regimen and patient adherence. A mandatory post-marketing surveillance was conducted in Korea to monitor the safety of Kivexa (lamivudine 300 mg/abacavir 600 mg). MATERIALS AND METHODS: An open label, multi-center, non-interventional post-marketing surveillance was conducted to monitor the safety of Kivexa from July 2011 to July 2017 in 23 hospitals in Korea. Subjects over 12 years old taking Kivexa per prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events during the study period. Secondary outcomes included the occurrence of adverse drug reaction, the occurrence of serious adverse events and the effectiveness of Kivexa. RESULTS: A total of 600 patients from 23 hospitals were enrolled within the 6 years of study. The total observation period was 1,004 person-years. Three hundred and ten patients reported 674 adverse events. The incidence of upper respiratory infection (65 cases, 10.9%) was the highest, followed by diarrhea (20 cases, 3.3%), and nausea (18 cases, 3.0%). 109 subjects reported 71 events of adverse drug reactions, and the most common reaction was nausea in 2.33% of the subjects. Thirty-one subjects reported serious adverse events, none of them were considered drug related. From the total of 600 subjects, excluding 48 subjects who were ‘effectiveness unassessable’ by investigators, 552 patients were eligible for the subjective effectiveness analysis. 459 (83.2%) were evaluated as ‘improved’. Proportion of subjects whose human immunodeficiency virus-RNA is <50 copies/ml was 61.2% (309/505) at the beginning of observation and increased to 91.9% (464/505) at the end of study period. CONCLUSIONS The post-marketing surveillance showed the safety of Kivexa in HIV-1 patients in Korea. Ischemic cardiovascular events and hypersensitivity associated with Kivexa were few. There was no significant new safety information. This data may be helpful in implementing Kivexa and lamivudine/abacavir sulfate containing drugs in Korea.

BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. RESULTS: BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10⁻¹¹ for BLK, and OR, 1.26; p=1.42×10⁻⁴ for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10⁻⁵). CONCLUSIONS KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD.