Safety of COVID-19 Vaccination During Pregnancy and Lactation: A VigiBase Analysis

Background@#There is limited evidence on the safety of coronavirus disease 2019 (COVID-19) vaccination during pregnancy and lactation. Thus, we aimed to evaluate the association between COVID-19 vaccination during pregnancy and lactation and reporting risk of adverse pregnancy or lactation outcomes. @*Methods@#Using VigiBase, we performed a disproportionality analysis with caseon case design. Cases were defined based on the Standardized MedDRA Queries (SMQs) of “pregnancy and neonatal topics” and non-cases were defined as all other adverse events. We included all reports with COVID-19 vaccines as the suspected cause. Using the full database as the comparators, reporting odds ratios (RORs) with 95% confidence intervals (CIs) were estimated by logistic regression while adjusting for maternal age. Infants’ age and sex were additionally adjusted in analyzing the risk of COVID-19 vaccination during lactation. @*Results@#We identified 10,266 and 6,474 reports with the SMQ of “pregnancy and neonatal topics” associated with COVID-19 vaccines during pregnancy and lactation, respectively. No significant RORs of adverse pregnancy outcomes associated with COVID-19 vaccines during pregnancy were observed; however, “functional lactation disorders” showed significant disproportionality during lactation with adjusted ROR of 1.48 (95% CI, 1.21–1.79). Further analysis that analyzed “functional lactation disorders” at a preferred term level, showed higher ROR in mastitis (2.76 [95% CI, 1.45–5.27]). @*Conclusion@#Overall, we did not observe a positive association between COVID-19 vaccination during pregnancy and risk of reporting adverse pregnancy outcomes. However, we found a significant disproportionate reporting association between COVID-19 vaccination during lactation and “functional lactation disorders”, specifically mastitis. Continuous surveillance is warranted to confirm the safety of COVID-19 vaccine during pregnancy and lactation.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study

Background@#Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. @*Methods@#We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. @*Results@#Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65–1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60–4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60–4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. @*Conclusion@#This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Cardiovascular Safety of COVID-19 Vaccination in Patients With Cancer:A Self-Controlled Case Series Study in Korea

Background@#Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea. @*Methods@#We conducted a self-controlled case series study using the K-COV-N cohort (2018– 2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0–28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI). @*Results@#Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90–1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95–1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83–1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68–1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88–23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis. @*Conclusion@#For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.

Adverse Events Following COVID-19Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase

Background@#During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. @*Methods@#In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization’s global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12–17 years, ICSRs following any vaccines on adolescents aged 12–17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. @*Results@#Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents;myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05–27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89–9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72– 1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44–0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59–2.09) were not significantly higher following COVID-19 vaccination. @*Conclusion@#In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

The COVID-19 Vaccine Safety Research Center: a cornerstone for strengthening safety evidence for COVID-19 vaccination in the Republic of Korea

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC’s initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC’s second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol:Nested Case-Control and Case-Time-Control Studies

Purpose@#Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. @*Materials and Methods@#We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens–Johnson syndrome (SJS), using the claims database of South Korea, 2010–2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. @*Results@#We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71–3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09–3.47). @*Conclusion@#In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

Short-term safety profile of COVID-19 vaccination in children and adolescents with underlying medical conditions: a prospective cohort study

Purpose@#This article was to collect data on the safety of coronavirus disease 2019 (COVID-19) vaccines in children with underlying medical conditions. @*Methods@#We constructed a prospective cohort of children and adolescents aged 5 to 19 years who had received at least one dose of COVID-19 vaccine. Patients diagnosed with and treated for chronic kidney disease, autoimmune disease, or other chronic conditions at the Seoul National University Children’s Hospital were recruited from June to December 2022. A mobile survey questionnaire was sent to their guardians. The presence of adverse events on the day (day 0), 3 weeks (day 21), and 6 months (day 180) after the 1st dose of COVID-19 vaccine was recorded by the guardians. @*Results@#A total of 73 children participated. The median age was 14 years, and 64.4% of the patients were male. On the day of immunization, 65.8% of the patients reported at least one adverse event. Pain at the injection site, fatigue, headache, arthralgia, and myalgia were the most common symptoms. The prevalence of adverse events decreased over time (65.8% on day 0, 27.4% between days 0 and 21, and 24.6% between days 21 and 180). Severe acute respiratory syndrome coronavirus 2 infection after the 1st dose occurred in 17 patients (23.3%) and one of the patients (5.88%) was hospitalized due to infection. @*Conclusions@#Adverse events after COVID-19 vaccination were generally mild in children and adolescents with underlying medical conditions. Our findings provide evidence for the safety of COVID-19 vaccination in the vulnerable pediatric population.

Effectiveness and Safety of COVID-19 Vaccination During Preconceptional and Preclinical Pregnancy Period: A National Population Study

Background@#We aimed to assess the risk of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and early abortive outcomes after the association between coronavirus disease 2019 (COVID-19) vaccination during the preconceptional period and preclinical pregnancy, which are likely to be inadvertent vaccination. @*Methods@#We used data from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort from December 2020 to December 2021. The vaccinated pregnant women were matched to unvaccinated pregnant controls at a 1:4 ratio.The risks of SARS-CoV-2 infection and intensive care unit (ICU) admission within 14 days of infection were analyzed to assess its effectiveness. For safety measures, the adjusted relative risks (aRRs) of early abortive outcomes for the first COVID-19 vaccination during the preconceptional and preclinical periods were calculated considering covariates. We compared the risk of early abortion between mRNA and viral vector vaccines. @*Results@#The overall COVID-19 vaccination rates during the preconceptional period and preclinical pregnancy were 3.1% (6,662/215,211) and 2.6% (5,702/215,211), respectively.The cumulative incidence of ICU admission within 14 days of SARS-CoV-2 infection was 6/100,000 in the unvaccinated group, whereas there were no ICU admissions in the vaccinated groups. The risks of early abortive outcomes were not significantly different between the preconceptional vaccination group and the unvaccinated group (aRR, 1.04; 95% confidence interval [CI],0.99–1.10) or between preclinical pregnancy vaccination and their matched controls (1.02; 95% CI, 0.96–1.08). mRNA and viral vector vaccines have shown similar risks for early abortive outcomes and miscarriages. @*Conclusion@#Our findings have provided compelling evidence regarding the effectiveness and safety of COVID-19 vaccination prior to and during early pregnancy. Further research is required to extend the safety and efficacy profiles of COVID-19 vaccines to pregnant women and their babies.

Predictors of COVID-19 Vaccine Hesitancy Among Parents of Children Aged 5–11 Years in Korea

This was a cross-sectional study using the data collected from a nationwide survey between November and December 2022 to explore factors associated with hesitancy towards coronavirus disease 2019 (COVID-19) vaccination for children. Among 3,011 participants with child aged 5–11 years, 82.5% demonstrated hesitancy towards vaccinating their child. This was more common among mothers (odds ratio 1.84 [95% confidence interval 1.46–2.31]), those residing outside metropolitan area (urban: 2.46 [1.89–3.20]; rural: 2.87 [2.09–3.93]) or with history of COVID-19 diagnosis (2.22 [1.78–2.76]). Parents were also hesitant if their child recently had COVID-19 (3.41 [2.67–4.37]). Conversely, they were less likely to be hesitant if they had three or more children (0.66 [0.46–0.94]) or if their child has underlying medical condition(s) (0.54 [0.41–0.71]). Our findings highlight high prevalence of parental hesitancy towards COVID-19 vaccination for children, and call for targeted outreach efforts from the stakeholders to facilitate the vaccine uptake in this pediatric population.

A Nationwide Survey of mRNA COVID-19 Vaccinee’s Experiences on Adverse Events and Its Associated Factors

Background@#Although coronavirus disease 2019 (COVID-19) vaccines have been distributed worldwide under emergency use authorization, the real-world safety profiles of mRNA vaccines still need to be clearly defined. We aimed to identify the overall incidence and factors associated with adverse events (AEs) following mRNA COVID-19 vaccination. @*Methods@#We conducted web-based survey from December 2 to 10 in 2021 with a 2,849 nationwide sampled panel. Study participants were individuals who had elapsed at least twoweeks after completing two dosing schedules of COVID-19 vaccination aged between 18–49 years. We weighted the participants to represent the Korean population. The outcome was the overall incidence of AEs following mRNA COVID-19 vaccination and associated factors.We estimated the weighted odds ratios (ORs) using multivariable logistic regression models to identify the factors associated with AEs. @*Results@#Of the 2,849 participants (median [interquartile range] age, 35 [27–42] years; 51.6% male), 90.8% (n = 2,582) for the first dose and 88.7% (n = 2,849) for the second dose reported AEs, and 3.3% and 4.3% reported severe AEs, respectively. Occurrence of AEs was more prevalent in mRNA-1273 (OR, 2.06; 95% confidence interval [CI], 1.59–2.67 vs. BNT162b2), female sex (1.88; 1.52–2.32), and those with dermatologic diseases (2.51; 1.32–4.77). History of serious allergic reactions (1.96; 1.06–3.64) and anticoagulant medication use (4.72; 1.92–11.6) were associated with severe AEs. @*Conclusion@#Approximately 90% of participants reported AEs following mRNA COVID-19 vaccination. Substantial factors, including vaccine type (mRNA-1273), female sex, and dermatologic diseases were associated with AEs. Our findings could aid policymakers in establishing vaccination strategies tailored to those potentially susceptible to AEs.

Trends in Prescribing of Antiseizure Medications in South Korea: Real-World Evidence for Treated Patients With Epilepsy

Background@#and Purpose We investigated the trends in the prescribing of antiseizure medication (ASM) over a 9-year period, and provide real-world data regarding ASM prescriptions of patients with epilepsy in South Korea. @*Methods@#This study used data in the Korean National Health Information Database for the period from 2009 to 2017. We included 18 oral ASMs, which were classified into older and newer ASMs based on them first becoming available on the market before or after 1991, respectively. The annual trends in ASM prescriptions were plotted over the 9-year study period, and changes in these trends were evaluated as average annual percentage changes (AAPCs) using Poisson regression. Age- and sex-stratified analyses were also conducted. @*Results@#Overall, the proportion of prescriptions involving polytherapy with three or more ASMs increased from 10.08% in 2009 to 10.99% in 2017 (AAPC=0.9%, p<0.001) over the 9-year study period. Among monotherapies, although valproate (VPA) was the most frequently prescribed ASM, the prescription rate of levetiracetam (LEV) steadily increased regardless of age and sex over the study period. The monotherapy prescription trends differed depending on age and sex. In the five most frequently used ASM combination regimens, the prescription rates of VPA/LEV, LEV/oxcarbazepine, and LEV/lamotrigine regimens showed increasing tendencies. In contrast, prescription rates for all combined regimens of older ASMs declined over time in all age groups. @*Conclusions@#This is the first epidemiological study of the changes in prescription trends for ASM in South Korea based on nationwide data from 2009 to 2017. We found progressive increases in the use of newer ASMs for both monotherapy and duotherapy, and for polytherapy with three or more ASMs over the 9-year study period.

Increasing Trends in the Incidence and Prevalence of Epilepsy in Korea

Background@#and Purpose There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009–2017. @*Methods@#This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). @*Results@#The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). @*Conclusions@#There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.

Survival, Prognosis, and Clinical Feature of Refractory Myasthenia Gravis: a 15-year Nationwide Cohort Study

Background@#Myasthenia gravis (MG) is a rare classic autoimmune disease where immunosuppressant therapies have been successful to reduce MG attributable mortality fairly well. However, patients with refractory MG (rMG) among the actively treated MG (aMG) are nonresponsive to conventional therapy and display high disease severity, which calls for further research. We aimed to determine survival, prognosis, and clinical feature of patients with rMG compared to non-rMG. @*Methods@#Retrospective nationwide cohort study using Korea's healthcare database between 2002 and 2017 was conducted. Patients with rMG (n = 47) and non-rMG (n = 4,251) who were aged > 18 years, followed-up for ≥ 1 year, and prescribed immunosuppressants within 2 years after incident MG diagnosis were included. Patients with rMG were defined as administered plasma exchange or intravenous immunoglobulin at least 3 times per year after receiving ≥ 2 immunosuppressants. All-cause mortality, myasthenic crisis, hospitalization, pneumonia/ sepsis, and emergency department (ED) visits were measured using Cox proportional hazard models and pharmacotherapy patterns for rMG were assessed. @*Results@#The rMG cohort included a preponderance of younger patients and women. The adjusted hazard ratio was 2.49 (95% confidence interval, 1.26–4.94) for mortality, 3.14 (2.25–4.38) for myasthenic crisis, 1.54 (1.15–2.06) for hospitalization, 2.69 (1.74–4.15) for pneumonia/sepsis, and 1.81 (1.28–2.56) for ED visits for rMG versus non-rMG. The immunosuppressant prescriptions were more prevalent in patients with rMG, while the difference was more remarkable before rMG onset rather than after rMG onset. @*Conclusion@#Despite the severe prognosis of rMG, the strategies for pharmacotherapeutic regimens were similar in those two groups, suggesting that intensive monitoring and introduction of timely treatment options in the early phase of MG are required.

Exploring the Perception on Drug Utilization Review System and DUR Modernization Pilot Project: A Qualitative Study Using Focus Group Interviews

Objective@#To explore the perception of drug utilization review (DUR) system and DUR modernization pilot project among healthcare professionals and patients. @*Methods@#We conducted 8 times of focus group interviews (FGI) between August 1, 2019 to December 31, 2019. The healthcare professionals and patients who participated in the DUR modernization pilot project were included in the present study. Based on the type of project participation or medical institution, the participants were divided into the following four groups: group 1, hospital; group 2, clinic; group 3, pharmacy; and group 4, patient. Within each group, interviews were conducted under a pre-defined agenda to identify the implicit perceptions of the participants; the contents of the interviews were, then, categorized. @*Results@#Healthcare professionals established a consensus on the positive aspects of the DUR system and DUR modernization pilot project. However, substantial concerns remain, such as additional workload associated with monitoring adverse events or acquiring consents from patients. Furthermore, a difference of opinion over the DUR convenience system was observed. Among 3 DUR convenience system, the personal medication history review service was highly utilized, but pop-up hold function and communication system was rarely used. @*Conclusion@#We observed that systematic intervention using the DUR system is effective for both healthcare providers and consumers. Adverse events caused by inappropriate drug use can be prevented by continuous patient monitoring. Therefore, the role of DUR system needs to be expanded to establish a safe drug management system.

A survey for Management of Drug Safety Evaluation System for Investigational Product

Objective@#To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. @*Methods@#We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. @*Results@#All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. @*Conclusion@#All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Treatment Patterns of Osteoporosis and Factors Affecting the Prescribing of Bone-forming Agents: From a National Health Insurance Claims Database

Objective@#To analyze osteoporosis treatment patterns and teriparatide prescription-associated factors in Korea by using a national health insurance claims database. @*Methods@#We utilized the Health Insurance Review & Assessment Service National Patients Sample claims database to identify patients (aged ≥50 years) with at least one osteoporosis claim (International Classification of Disease 10th revision code: M80, M81, M82) and at least one prescription for osteoporosis medication (antiresorptive agents:bisphosphonates, selective estrogen receptor modulators, denosumab, and calcitonin; bone-forming agent: teriparatide) in 2018. Demographic characteristics and healthcare utilization patterns were analyzed. Factors associated with teriparatide prescriptions were assessed using a multivariate logistic regression model. @*Results@#Records showed that 44,815 patients were prescribed osteoporosis medications in 2018; the percentage of patients prescribed each treatment was as follows: 86.6% bisphosphonates, 13.9% selective estrogen receptor modulators, 3.1% calcitonin, 2.1% denosumab, and 0.7% teriparatide. A greater proportion of patients prescribed teriparatide were ≥75 years (53.4% vs. 33.8%) and had fractures (63.9% vs. 12.8%) compared to the same for antiresorptives (p<0.001). Patients prescribed teriparatide had higher Charlson comorbidity index values (1.2±1.3 vs. 0.9±1.2) and were more frequently hospitalized (0.8±1.3 vs. 0.1±0.5) than those prescribed antiresorptives (p<0.001). Elderly patients (≥75 years old; adjusted OR=1.66; 95% CI 1.16-2.38) and those with fractures (adjusted OR=6.23; 95% CI 4.76-8.14) were more likely to be prescribed teriparatide than antiresorptives. @*Conclusion@#Patients prescribed teriparatide were older and more likely to have severe osteoporosis than those prescribed antiresorptives.

Arthralgia and Myalgia Associated with the Use of Bisphosphonate:An Active Monitoring Study

Objective@#We investigated arthralgia and myalgia associated with the use of oral bisphosphonate (BP) by conducting a survey of patient. @*Methods@#The pharmacists conducted a survey between 1 Oct 2019 and 30 Sep 2020 among patients who were dispensed BP in community pharmacies to assess their demographic and medical characteristics, and their experiences with, and process for pain. Logistic regression analyses were performed to find the risk factors associated with the pain, and the odds ratios (OR) and 95% confidence intervals (CI) were determined. @*Results@#A total of 160 patients who used BP participated in the survey (74 [46.3%] used risedronate; 61 [38.1%] used alendronate; 23 [14.4%] used ibandronate), and 20 (12.5%) of them experienced pain. Significant statistical differences of the characteristics between patients who experienced pain or not were observed regarding menopause, and parity. Compared with women who had one or two parity, women who had more than three parity were associated with the decreased risk of pain (OR, 0.24; 95% CI, 0.04-0.98). Moreover, steady exercise was associated with the decreased risk of pain compared to less exercise (OR, 0.37; 95% CI, 0.14-0.98). @*Conclusion@#Our findings suggest that the risk of pain in BP-treated patients might be different regarding the different ingredients of BP, and dosing frequency. This survey highlights a need for a further safety research to understand the factors influencing the pain associated with the BP treatment.

10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea

Background@#In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015. @*Methods@#BMD was classified as normal (T-score ≥–1.0 standard deviation [SD]), osteopenia (T-score –2.5 SD), and osteoporosis (T score ≤–2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD. @*Results@#Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD. @*Conclusion@#Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study

Background/Aims@#Although anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians. @*Methods@#Using the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy. @*Results@#A total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60). @*Conclusions@#More than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab

Trend of Antibiotic Use in Children with Acute Otitis Media in Korea

Public interventions have shown to optimize the use of antibiotics in children with acute otitis media (AOM). In this study, we describe the AOM-related antibiotic use among children in South Korea using national cohort data. We retrieved the Health Insurance Review & Assessment Service data to construct a national cohort of children aged 0–6 years who had been diagnosed with AOM between 2012 and 2018. Of 25,212,264 children included, the antibiotic prescription has increased for amoxicillin/amoxicillin-clavulanate from 56.1% in 2012 to 61.8% in 2018. Prescription has decreased for cephalosporin (35.1% in 2012 to 31.8% in 2018) and macrolide (8.7% in 2012 to 6.4% in 2018). National cohort data have shown an increased trend in AOM-related aminopenicillin prescription and downward trend cephalosporin and macrolide use in South Korea. A multi-faceted approach is required to control the antimicrobial resistance at a population level.