Sanofi (South Korea)

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m 2 , oxaliplatin 100 mg/m 2 intravenously day 1, S-1 40 mg/m 2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

BACKGROUND: Hyperuricemia accompanying tumor lysis syndrome is a serious complication in neoplasia with rapid proliferation and destruction. To confirm the efficacy of recombinant urate oxidase (rasburicase) and its safety profile, a phase IV compassionate use prospective study was performed in Korean pediatric patients with hematologic malignancies. PROCEDURE: Rasburicase was administered at 0.2 mg/kg/day once daily for 3-5 days (twice daily allowed during the first 72 hr) by intravenous route for hyperuricemia (uric acid > 7.5 mg/dl). The study period was 5 weeks and consisted of a baseline assessment within 48 hr before the administration of rasburicase, 3-5 days of assessment during treatment and a follow-up assessment at 4 weeks after its final administration. RESULTS: The uric acid endpoint (< or =7.0 mg/dl) was reached in 97.3% (36/37) of the patients and uric acid levels were significantly reduced in all patients (P < 0.001). Drug related toxicities were mild and reversible without any grade 4 or serious adverse event associated with rasburicase. CONCLUSION: This study confirms that rasburicase is a safe and effective agent for the treatment of hyperuricemia associated with hematologic malignancies in pediatric patients.

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

BACKGROUND: The aim of the present 24-week multicentre randomized non-inferiority trial was to compare the efficacy and safety of two insulin intensification strategies in uncontrolled type 2 diabetes despite optimized basal insulin therapy. METHODS: Patients with fasting plasma glucose (FPG) <130 mg/dL and HbA1c 7.0%-10.0% while on insulin glargine were randomized to a basal-prandial group (stepwise addition of insulin glulisine) or a premixed insulin group (insulin aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The primary endpoint was the change in HbA1c after 24 weeks (non-inferiority margin 0.4%). RESULTS: At Week 24, the adjusted mean change from baseline HbA1c was -0.94 ± 0.09% and -1.04 ± 0.09% in basal-prandial and premixed insulin groups, respectively, with a mean difference of -0.09% (95% confidence interval [CI] -0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was observed during stabilization of the total daily insulin dose in the premixed insulin group (Weeks 0-12). After stabilization of the total daily insulin dose, the rate of hypoglycemia and the total daily insulin dose were similar in the two groups. CONCLUSIONS: The efficacy and safety of the two intensifying regimens were similar after stabilization of the total daily insulin dose when oral agents were maintained. Starting with a lower total daily insulin dose with a gradual change in the treatment regimen was helpful in reducing the rate of hypoglycemia during initial stabilization of the total daily insulin dose.

Endomyocardial biopsy often fails to show myocardial inflammation for patients with clinically suspected myocarditis. The serum isoforms of troponin T (cTnT) level is a very sensitive marker of myocardial injury and it is elevated even in the absence of myocardial inflammation. We investigated the correlations for myocardial injury, virus titers and inflammation in acute viral infection. Using the murine coxsackievirus group B3 (CVB3) myocarditis model, the histopathologic findings and virus titers in mouse hearts were compared with the serum cTnT levels measured by ELISA at various time points. Viable virus titers in the hearts peaked at 3 days after infection (8.22 +/- 0.13 log10 PFU/100 mg of heart); they decreased at day 7 and no viable virus was detected from day 14. Myocardial inflammation was minimal at day 3, peaked at day 7 and markedly decreased at day 14. The individual serum TnT levels were significantly increased at day 3 (7.37 +/- 1.46 ng/ml), persisted to day 7 (0.73 +/- 0.08 ng/ml), and normalized at day 14. Serum cTnT levels were correlatable with virus titers in the heart (r = 0.744, P <0.01), but the serum cTnT levels were not correlated with the degrees of inflammation. Using the less myocarditic strain of CVB3, similar relationships were observed between the changes for the serum cTnT levels and the heart virus titers. During the course of viral infection, myocardial injury precedes the pathologic evidence of inflammation, and the elevated cTnT levels provide evidence of myocardial injury even in the absence of any histologic findings of myocarditis.

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, "a little" changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either "moderate" or "very much" change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

BACKGROUND: Countries with strong vaccination programmes, including the Republic of Korea, have experienced changes in the epidemiology of Japanese encephalitis (JE), with an increase in cases seen among adults. However, the reasons for this increase are not clearly understood. This study describes the change in age-specific JE virus (JEV) seroprevalence over time in Korea, with a view to understanding this transition. METHODS: A search of Embase, MEDLINE, PubMed, KoreaMed, Korea Education and Research Information Service, National Library of Korea, and the Seoul National University Medical Library was conducted using the keywords 'Japanese encephalitis' combined with 'Korea', 'seroprevalence', 'seropositivity', 'seroepidemiology', 'serosurvey', 'immunity', and 'antibody'. RESULTS: Eighteen studies published between 1946 and 2012 were retrieved. In 1946, seropositivity was 51% in the 1-10 years age group, 79% in those aged 11-20 years, and 94% in those ≥61 years of age. In the 1970s, seropositivity in children and adolescents was low (10-59%); seropositivity in this group increased to 90-92% in 1984-1985, and increased further to 98% in 2012. Seropositivity among adults aged 41-50 years and 51-60 years in the 2010s ranged between 83.1% and 97.9% and between 77.5% and 98.3%, respectively. CONCLUSIONS: The implementation of the universal JE vaccination programme in the 1980s has increased the seroprevalence of JEV in Korea, especially in children who are targeted for vaccination.

VaxigripTetra® (Sanofi Pasteur, Lyon, France) is a quadrivalent split-virion inactivated influenza vaccine (IIV4) containing two B-lineage strains approved in the European Union and Taiwan in 2016 for individuals ≥ 3 years of age. Here, we describe an observer-blind, randomized, controlled, multicenter trial study evaluating the immunogenicity and safety of the Northern Hemisphere 2015-2016 formulations of IIV4 and the licensed split-virion trivalent inactivated influenza vaccine (IIV3) in the Republic of Korea (ClinicalTrials.gov no. NCT02550197). The study included 300 Korean adults 18-60 years of age randomized 2:1 to receive a single injection of IIV4 or IIV3. For each of the four vaccine strains in IIV4, 21 days after vaccination, geometric mean post-/pre-vaccination ratios of hemagglutination inhibition titers were ≥ 3.97. Seroconversion/significant increases rates were ≥ 40% for all but the A/H1N1 strain, for which the rate was 39.7%. Results were similar for the three strains in IIV3. For the additional B-lineage strain not in IIV3 (Victoria), hemagglutination inhibition antibody titers were higher for IIV4 than for IIV3. Solicited reactions and adverse events were similar between IIV4 and IIV3, and no serious adverse events or new safety signals were detected. These results confirm the robust immunogenicity and acceptable safety of IIV4 in adults 18-60 years of age and show that including a second B-lineage strain should provide broader protection against B-strain influenza without affecting vaccine safety or the immunogenicity of other three vaccine strains.

4067 Background: The phase 3 PRODIGY study compared neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy followed by surgery followed by adjuvant S-1 with surgery followed by adjuvant S-1 for Korean patients with resectable locally advanced gastric cancer (LAGC) (Kang et al. J Clin Oncol. 2021). The planned analysis of the primary endpoint of PRODIGY showed that the addition of neoadjuvant DOS to surgery and adjuvant S-1 improved progression-free survival (PFS). We herein report the long-term follow-up outcomes, including overall survival (OS), from this trial. Methods: Patients with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma with clinical T2-3N+ or T4Nany disease were enrolled from 18 Korean study sites. Patients were randomly assigned to D2 surgery followed by adjuvant S-1 (40–60 mg orally twice a day, days 1–28 q6w for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m 2 , oxaliplatin 100 mg/m 2 intravenously day 1, S-1 40 mg/m 2 orally twice a day, days 1–14 q3w for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary endpoint was PFS. OS was the secondary endpoint. This analysis presents the final assessment of the outcomes after 5 years. Results: A total of 266 and 264 patients were randomly assigned to the CSC and SC arms, respectively, among which 238 and 246 patients were treated and included in the full analysis set. As of the data cut-off date (SEP-2022), the median follow-up duration of the surviving patients was 99.5 months (range, 68.6–127.7 months). As compared to SC, CSC significantly increased the OS (adjusted hazard ratio, 0.72; 95% CI, 0.54 to 0.97; stratified log-rank P=0.028) with a 5-year OS rate of 66.8% and 63.0% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (adjusted hazard ratio, 0.71; 95% CI, 0.53 to 0.94; stratified log-rank P=0.019) with a 5-year PFS rate of 60.6% and 56.9% for the CSC and SC arms, respectively. Conclusions: The addition of neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy, as part of perioperative chemotherapy, to surgery and adjuvant S-1 prolonged the OS and PFS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1 alone. Neoadjuvant DOS chemotherapy should be considered one of the standard treatment options for patients with LAGC in Asia. Clinical trial information: NCT01515748 .

OBJECTIVES: To assess the safety and immunogenicity of a meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) in a Korean population. METHODS: This was a phase III, blind-observer, controlled study in which participants aged 11-55 years were randomized (2:1 ratio) to a single dose of MenACYW-D or tetanus/diphtheria/acellular pertussis (Tdap) vaccine. Outcomes included rates of seroconversion against all serogroups (≥4-fold increase in antibody titer from pre-vaccination), geometric mean titers (GMTs) at days 0 and 28 based on a serum bactericidal assay using baby rabbit complement, rates of seroprotection (titer ≥1:128) at day 28, and safety. RESULTS: A total of 300 participants were enrolled in the study (200 MenACYW-D and 100 Tdap). Seroconversion rates for serogroups A, C, Y, and W-135 were 77.8%, 88.3%, 74.6%, and 92.4%, respectively, for the MenACYW-D group and 9.3%, 8.1%, 12.2%, and 8.2%, respectively, for the Tdap group. The proportions of participants with pre-vaccination titers ≥1:128 were 57.3%, 12.6%, 51.5%, and 22.2% for serogroups A, C, Y, and W-135, respectively; post-vaccination rates were 98.5%, 89.4%, 96.0%, and 95.0% for the MenACYW-D group. A lower proportion of participants reported solicited reactions with MenACYW-D (46.2%) compared with Tdap (76.8%). CONCLUSION: A single dose of MenACYW-D was well tolerated and elicited a robust immune response in Korean adolescents and adults.

BACKGROUND: This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). METHODS: In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. RESULTS: Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators' assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients' LDL-C levels was the primary reason for non-intensification of statin therapy. CONCLUSION: Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

BACKGRUOUND: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. METHODS: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. RESULTS: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. CONCLUSION: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

INTRODUCTION: The Korean National Health Insurance revised its reimbursement criteria to expand coverage for anti-osteoporotic drug treatments in 2011 (expanding diagnostic criteria and the coverage period for anti-osteoporotic therapy) and 2015 (including osteoporotic fracture patients regardless of bone mineral density). We examined whether the two revisions contributed to an increase in the prescription rates of anti-osteoporotic drugs in Korea. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Sample data from 2010 through 2016. A segmented regression analysis of interrupted time series was performed to assess changes in the monthly prescription rates of anti-osteoporotic drugs among women aged 50 or older, defined as the proportion of elderly women prescribed with anti-osteoporotic drugs. RESULTS: Both the levels (i.e., abrupt jump or drop) and the trends (i.e., slope) of the prescription rates of anti-osteoporotic drugs in the general population, osteoporotic patients, and osteoporotic fracture patients showed no significant changes after the first revision. However, there was a significant increase in the trends in the general population (β = 0.0166, p = 0.0173) and in osteoporotic patients (β = 0.1128, p = 0.0157) after the second revision. Women aged 65 to 79 years were the most significantly increased group in terms of the treatment proportion after the second revision because the trend was significant after the second revision in all three study populations (β = 0.0300, 0.1212, 0.1392, respectively; p < 0.05). CONCLUSIONS: Although the two revisions expanded reimbursement coverage, only the second revision on reimbursing based on osteoporotic fracture regardless of bone mineral density was associated with increasing the proportion of post-menopausal women being treated with anti-osteoporotic drugs.

BACKGROUND: This study aimed to evaluate cardiovascular risk in subjects with pre-diabetes and diabetes in Korea. METHODS: In this pan-Korean, non-interventional, cross-sectional study, data were collected from medical records of 10 hospitals between November 2013 and June 2014. Subjects (aged ≥40 years) with medical records of dysglycemia and documentation of total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, and smoking status in the past 6 months were included. The primary endpoint was to determine the Framingham risk score (FRS). The relationships between FRS and cardiovascular risk factors, glycated hemoglobin, and insulin usage were determined by multiple linear regression analyses. RESULTS: =0.002) among subjects with pre-diabetes (n=306) in comparison to subjects without these coexisting risk factors. CONCLUSION: Overall, Korean subjects with pre-diabetes and diabetes have an increased cardiovascular risk, which is significantly higher in those subjects with diabetes than with pre-diabetes. The present data can be used to develop measures to prevent and manage cardiovascular complications in Koreans with impaired glucose metabolism.

PURPOSE: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. MATERIALS AND METHODS: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. RESULTS: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. CONCLUSION: Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

BACKGROUND: This study evaluated the effect of a booster vaccination of a new, live attenuated, Japanese encephalitis chimeric vaccine (JE-CV). Previously this vaccine has been used as a booster 12 months after priming with an inactivated vaccine and at >24 months after priming with the same JE-CV. This study evaluates the immunogenicity and safety of the JE-CV given at 12-24 months after JE-CV priming. METHODS: Phase III, open-label study in the Republic of Korea in which 119 children previously vaccinated with JE-CV at 12-24 months of age received a JE-CV booster at 12-24 months after primary vaccination. JE neutralizing antibody titers were measured using >50% plaque reduction neutralization test prebooster and 1 month postbooster vaccination. Seroprotection (SP) was defined as ≥10 (1/dil). Safety was assessed for 28 days postvaccination by parental reports. Serious adverse events were monitored for 6 months postvaccination. RESULTS: Antibody persistence was high prebooster (SP rate 93.5%). There was a strong anamnestic response postbooster vaccination, with an SP rate of 100% and a >50-fold increase in geometric mean titer from the prebooster level. Both antibody persistence and the booster response were independent of whether the booster was given at 12-17 or 18-24 months. The safety profile was good and comparable with the primary vaccination; there were no vaccine-related serious adverse events and no deaths. CONCLUSIONS: This study confirms the suitability of a JE-CV booster vaccination at 12-24 months after a primary dose of the same vaccine given at 12-24 months of age in children in the Republic of Korea.

INTRODUCTION: PENTAXIM™ (Sanofi), DTaP-IPV//Hib, a pentavalent combination vaccine for protection against diphtheria, tetanus, pertussis, poliomyelitis, and invasive infections caused by Haemophilus influenzae type b, has been licensed in South Korea by the Ministry of Food and Drug Safety (MFDS) on May 9, 2016, and is currently used in routine vaccination. The aim of this phase IV study, conducted as a post-licensure commitment in South Korea, was to evaluate the safety of the DTaP-IPV//Hib vaccine when administered in infants at 2, 4, and 6 months of age in the real-world clinical practice. METHODS: This multicenter, observational, post-marketing surveillance (PMS) study was conducted in real-world practice in South Korea. Infants aged 2 months or older were enrolled across seven centers from July 31, 2018 to February 11, 2020. The study outcomes included occurrence, time to onset, duration, intensity, and causality assessment (for unsolicited adverse events [AEs] only) for several pre-listed solicited injection-site and systemic reactions, unsolicited AEs, and serious adverse events (SAEs). RESULTS: Data from 619 participants were included in the safety analysis. Overall, 618 AEs were reported by 273 (44.1%) participants consisting of 121 solicited injection-site reactions (15.4%), 344 solicited systemic reactions (24.6%), and 153 unsolicited AEs (15.7%) of which, 124 were unexpected AEs (12.9%) (regardless of intensity). None of the unsolicited AEs were reported to have a causal relationship with the study vaccine. One SAE of pyrexia (solicited reaction) was reported. Most AEs were of mild intensity, and all participants recovered. CONCLUSION: This PMS study of the DTaP-IPV//Hib vaccine confirmed its safety profile in a real-life setting in South Korea and justified that the vaccine is well tolerated when used in infants aged 2 months or older for the primary series.

INTRODUCTION: ) has been approved in South Korea for use in subjects aged ≥ 12 months since 2015. As part of the license agreement, a post-marketing surveillance study was undertaken to actively monitor the safety profile of JE-CV in the Korean population. METHODS: An observational, active safety surveillance study was conducted from 3 April 2015 through to 2 April 2019 at 12 centers in South Korea. Subjects aged ≥ 12 months who received a single dose of JE-CV (primary or booster) during a routine healthcare visit were recruited and followed up for solicited reactions (7 and 14 days for injection site and systemic reactions, respectively), non-serious unsolicited adverse events and serious adverse events within 42 days after vaccination. RESULTS: Overall, 810 subjects who received JE-CV were included in our analysis, the majority received the vaccine as a primary vaccination (94.9%; 769/810). There were 179 solicited reactions reported by 111 subjects; the majority of solicited reactions occurred within 0-3 days (80.4%; 144/179), were of 1-3 days' duration (79.3%; 142/179) and of grade 1 intensity (70.9%; 127/179). There were three grade 3 adverse reactions (irritability, pyrexia and malaise); all resolved within a few days. The incidence of solicited reactions were highest in those aged 12 to < 24 months (34.7% [52/150] subjects; 107 events) and 2 to < 10 years (17.8% [8/45] subjects; 14 events). All unsolicited adverse events (serious and non-serious) were unrelated to vaccination. There were no discontinuations due to adverse reactions/events. CONCLUSION: JE-CV has a good safety profile under practice conditions in South Korea. No new safety issues were identified. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02933710.

The highdose quadrivalent influenza vaccine (QIVHD) has shown improved protection against influenza and its complications in older adults. We aimed to evaluate the costeffectiveness of QIVHD compared with QIVSD among Korean adults aged ≥ 65 years in reducing influenzarelated disease burden. We evaluated the 2016/2017 and 2017/2018 seasons and their average values using a static decision tree model. The difference in efficacy between standard-dose (SD) and high-dose (HD) was calculated based on the results of a clinical trial comparing Fluzone® High-Dose Vaccine and Fluzone® Vaccine in older adults. Incremental cost-effectiveness ratios (ICERs) were assessed from the healthcare system perspective. A discount rate of 4.5% was applied to life-year-gained (LYG) values and utilities. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economic sources of uncertainty. In the analysis of the 2017/2018 season, the QIV-HD strategy generated an excess of 0.00182 life-years (Lys)/person and 0.003953 quality-adjusted life-years (QALYs)/person compared with QIV-SD. The ICER was 6,467.56 United States Dollars (USD)/QALY. In the analysis from the 2016/2017 season, QIV-HD caused a surplus of 0.00117 Lys/person and 0.003272 QALYs/person compared with QIV-SD. ICER was 7,902.46 USD /QALY. From the average data of the 2016/2017 and 2017/2018 seasons, an excess of 0.00147 Lys/person and 0.003561 QALYs/person were generated using QIV-HD compared with QIV-SD, while the ICER was 7,190.44 USD /QALY. From the healthcare system perspective, QIV-HD was a more cost-effective vaccination option in reducing influenza-related disease burden and healthcare costs in Koreans aged ≥ 65 years compared with QIV-SD.

BACKGROUND/AIMS: Efficacy and safety data of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), is not yet well established in the Korean population. We assessed them in ODYSSEY-KT through the pre-specified Korean subanalysis. METHODS: In the ODYSSEY-KT study, South Korean and Taiwanese patients with hypercholesterolemia and high cardiovascular risks were randomized (1:1) to alirocumab or placebo. Alirocumab was self-administered subcutaneously at 75 mg every 2 weeks with a maximally tolerated statin dose with or without other lipid-modifying therapies. Alirocumab dose was increased to 150 mg every 2 weeks at week 12 if low density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL at week 8. Primary endpoint was percent change in LDL-C from baseline to week 24. Results from Korean cohort (n = 83: 40 for alirocumab and 43 for placebo, respectively) analyses are reported here. RESULTS: In alirocumab group, the least square of mean change percent in LDL-C levels was -65.7% (placebo: 11.1%; p < 0.0001) and 92.0% of them achieved LDL-C < 70 mg/dL (placebo: 12.7%; p < 0.0001) at week 24. Alirocumab also showed significantly greater improvements in high density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, lipoprotein(a), and apolipoprotein B than placebo (p < 0.05). Two consecutive calculated LDL-C values < 25 mg/dL were observed in 37.5% of alirocumab-treated patients. Overall, 45.0% alirocumab-treated and 51.2% placebo-treated patients experienced treatment-emergent adverse events (TEAEs) without discontinuation of treatment due to TEAEs. CONCLUSION: Alirocumab has demonstrated to be effective in improvement of LDL-C and related lipid profiles in Korean cohort. Alirocumab was generally well tolerated with no significant safety signals.