Cost-Effectiveness of All-Oral Regimens for the Treatment of Multidrug-Resistant Tuberculosis in Korea: Comparison With Conventional Injectable-Containing Regimens

Background@#Regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) have been changed from injectable-containing regimens to all-oral regimens. The economic effectiveness of new all-oral regimens compared with conventional injectable-containing regimens was scarcely evaluated. This study was conducted to compare the cost-effectiveness between all-oral longer-course regimens (the oral regimen group) and conventional injectablecontaining regimens (the control group) to treat newly diagnosed MDR-TB patients. @*Methods@#A health economic analysis over lifetime horizon (20 years) from the perspective of the healthcare system in Korea was conducted. We developed a combined simulation model of a decision tree model (initial two years) and two Markov models (remaining 18 years, sixmonth cycle length) to calculate the incremental cost-effectiveness ratio (ICER) between the two groups. The transition probabilities and cost in each cycle were assumed based on the published data and the analysis of health big data that combined country-level claims data and TB registry in 2013–2018. @*Results@#The oral regimen group was assumed to spend 20,778 USD more and lived 1.093 years or 1.056 quality-adjusted life year (QALY) longer than the control group. The ICER of the base case was calculated to be 19,007 USD/life year gained and 19,674 USD/QALY. The results of sensitivity analyses showed that base case results were very robust and stable, and the oral regimen was cost-effective with a 100% probability for a willingness to pay more than 21,250 USD/QALY. @*Conclusion@#This study confirmed that the new all-oral longer regimens for the treatment of MDR-TB were cost-effective in replacing conventional injectable-containing regimens.

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.

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.

Signal Detection of Adverse Events Following Pneumococcal Vaccines from the Korea Adverse Event Reporting System Database, 2005–2016

PURPOSE: We aimed to analyze the surveillance reports of adverse events (AEs) due to different types of pneumococcal vaccines, in addition to detecting and validating signals of pneumococcal vaccines by comparing AEs with labels.MATERIALS AND METHODS: We analyzed the percentages of AEs according to vaccine type [pneumococcal polysaccharide vaccines (PPSVs) and pneumococcal conjugate vaccines (PCVs)] in children and adults using data from the Korea Adverse Event Reporting System (KAERS) database from 2005 to 2016. A signal was defined as an AE that met all three indices of data mining: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We validated the detected signals by calculating sensitivity, specificity, as well as positive and negative predictive values of the signals against label information.RESULTS: Of the 39933 AE reports on vaccination, 5718 (7.0%) were related to pneumococcal vaccine. The most frequent AE after vaccination with PPSV was fever (23.9%) in children and injection-site reaction in adults. The most frequent AE after vaccination with PCV in children was pharyngitis (26.2%). In total, 13 AEs met all three indices for signal detection. Among these, hypotension, apathy, sepsis, and increased serum glutamic oxaloacetic transaminase level were not listed on vaccine labels. In validation analysis, PRR and ROR performed slightly better than IC for adults who were vaccinated with PPSVs.CONCLUSION: Overall, 13 new signals of PPSVs, including four signals not listed on the labels, were detected. Further research based on additional AE reports is required to confirm the validity of these signals for children.

Benzodiazepine-Related Cognitive Impairment or Dementia: A Signal Detection Study Using a Case/Non-Case Approach

Objective@#The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a caseon-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. @*Methods@#Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). @*Results@#Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66–4.38). Higher ROR estimates were shown in female (2.33, 1.48–3.67) and in those with polypharmacy (2.20, 1.35–3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. @*Conclusion@#These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

Comparative Analysis of Ethical-the-counter Drugs and Over-the-counter Drugs for the Adverse Events from the Community Pharmacy

OBJECTIVE: To compare adverse event reporting patterns between ethical-the-counter and over-the-counter drugs from community pharmacies and outpatient settings. METHODS: We conducted a descriptive study using the adverse event reporting database, wherein data were collected from the regional pharmacovigilance centers of the Korean Pharmaceutical Association between January 1, 2016 and December 31, 2016. The reported drugs were classified into either ethical-the-counter or over-thecounter drugs, and we compared the distribution of patient age and gender, frequent adverse events and medications, serious adverse events, and causality assessment results, where causality assessments were performed according to the World Health Organization-The Uppsala Monitoring Centre's system. RESULTS: We included 17,570 reports (75,451 drug-adverse event pairs). Ethical-the-counter and over-the-counter drugs accounted for 81.4% and 18.6% of the total adverse event reports, respectively. The use of over-the-counter drugs was higher in females and patients aged 65 years. Alimentary tract and metabolism drugs, and respiratory system drugs were the most frequent ethical-the-counter and over-the-counter drugs, respectively. From causality assessment results, “possible” (75.4%) was the most commonly assigned category for ethical-the-counter drugs, while “possible” (44.0%) and “unlikely” (47.7%) were the most common categories for over-the-counter drugs. The distribution of serious adverse events were similar for both ethical-thecounter and over-the-counter drugs. CONCLUSION: Differences were observed in age, gender, reported medications, and symptoms for both ethical-the-counter and over-the-counter drugs. Further pharmacovigilance activities considering the adverse event characteristics of over-the-counter drugs, which are comparable to ethical-the-counter drugs, should be performed.