Earticle

Objective: This study aimed to provide efficacy and safety information on the use of erenumab for prevention of episodic and chronic migraines. Methods: The keywords “Erenumab and migraine” were used to search the PubMed database to then compile efficacy and safety data for erenumab. Data from relevant Phase 2 and Phase 3 clinical trials were analyzed, using RevMan for statistical analysis. Results: Three clinical trials (one Phase 2 and two Phase 3 studies) were retrieved. All three trials used the same primary endpoint (change from baseline in monthly migraine days (CBMD)) to evaluate efficacy and safety of erenumab use for prevention of episodic and chronic migraines. Subcutaneous doses of erenumab (70 or 140 mg) were administered monthly in each trial, for 3 months (Studies 2, and 3) or 6 months (Study 1). The mean differences in CBMD in the 70 mg and 140 mg erenumab arms were -1.36 and -1.98, respectively, compared to that in the placebo arm. Some adverse events, such as nasopharyngitis and upper respiratory tract infection, were reported, but no differences in safety between erenumab and placebo were found to be significant. Conclusions: Erenumab showed superior efficacy in prevention of migraines compared to placebo. However, additional information regarding the long-term safety of erenumab should be collected. Therefore, post-marketing surveillance for adverse events is needed.

Backgrounds: Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) increased prevalence and economic burden. Objectives: This study aimed to investigate drug use pattern in IBD patients in a real world. Methods: National Health Insurance claim data from 2010 to 2014 were used in this population-based study. All IBD patients diagnosed during study period were enrolled. IBD medications included 5-aminosalicylic acid (ASA), glucocorticoid, immunomodulator and anti-tumor necrosis factor-α agent(anti TNF-α). Growth rate of IBD prevalence, prescribed drug classes, duration of drug therapy and medication cost were analyzed. Number and percentage of patients for categorical variables, and mean and median for continuous variables were presented. Results: Total numbers of patients were 131,158 and 57,286 during 5 years, and their annual growth rate were 3.2 and 5.7% for UC and CD. UC and CD were prevalent in the 40-50 (41.2%) and 20-30 age groups (36.0%). About 60% of IBD patients was prescribed any of medications. 5-ASA was the most frequently prescribed, followed by corticosteroid and immunomodulator. Anti TNF-α use was the lowest, but 5 times higher than UC in CD. Combination therapies with different class of drugs were in 29% for UC and 62% for CD. Mean prescription days per patient per year were 306 and 378, and the median medication cost per patient per year was KRW 420,000 (USD 383) and KRW 830,000 (USD755), for UC and CD, respectively. Conclusions: Increasing prevalence of IBD requires further studies to contribute to achieve better clinical outcomes of drug therapy.

Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received 5 g/m2 MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or 150 μM MTX at 24 hours, and 2 or 5 μM at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > 100 μM showed higher percentage than group with MTX concentration < 100 μM (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at 150 μM MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at 2 μM, p = 0.024 at 5 μM). Conclusions: MTX concentrations greater than 100 μM show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that manifests as joint damage or athletic disability via sustained inflammation of the synovial membrane. The risk of cardiovascular disease (CVD) is higher in RA patients. This study aimed at evaluating the association between CVD comorbidities and RA by comparing a pharmacotherapy group with a nonpharmacotherapy group. Methods: Patient sample data from the Health Insurance Review and Assessment Service (HIRA-NPS- 2016) were used. Inverse probability of treatment weighting (IPTW) using the propensity score was used to minimize the differences in patient characteristics. Logistic regression analysis was used to evaluate the risk of CVD comorbidities. Results: The analyses included 1,207,213 patients, of which 33,122 (2.8%) had RA. The odds ratios (OR) of CVD comorbidities were increased in RA patients; ischemic heart disease (IHD: OR 1.75; 95% CI 1.73, 1.77), cerebral infarction (CERI: OR 1.28; 95% CI 1.26, 1.30), hypertension (HTN: OR 1.44; 95% CI 1.43, 1.45), diabetes mellitus (DM: OR 2.04; 95% CI 2.03, 2.06), and dyslipidemia (DL: OR 3.49; 95% CI 3.47, 3.51). The ORs of IHD, CERI, HTN, and DM in the traditional DMARD and biologic treatment groups were decreased, compared with those in the non-pharmacotherapy group. Conclusions: Thus, CVD risk was higher in RA patients, considering age, sex, and socioeconomic status. Appropriate pharmacotherapy could decrease the risk of CVD comorbidities in RA patients.

The purpose of this systematic review and meta-analysis was to assess the preventive effect of theophylline on acute kidney injury and the ameliorative effect of theophylline on renal function in asphyxiated neonates. A literature search of the PubMed/Medline, Embase, and Cochrane Library databases for information published up to February 2019 was conducted. All studies that reported the incidence rate of acute kidney injury, serum creatinine level, and glomerular filtration rate after the randomized administration of theophylline or placebo were included. In total, eight studies involving 498 neonates were eligible. The incidence rate of acute kidney injury was significantly lower in the theophylline group than in the placebo group (risk ratio [RR]: 0.42, 95% confidence interval [CI]: 0.32-0.55, p < 0.001). The changes in serum creatinine level in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 and 5 days of age (weighted mean difference [WMD]: -0.51, 95% CI: -0.62 to -0.40, p < 0.001, and WMD: -0.26, 95% CI: -0.34 to -0.18, p < 0.001, respectively). The changes in glomerular filtration rate in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 days of age and the last day of follow-up (WMD: 12.30, 95% CI: 9.39-15.21, p < 0.001, and WMD: 9.35, 95% CI: 6.43-12.27, p < 0.001, respectively). These results suggested that theophylline has a beneficial effect on the prevention of acute kidney injury in neonates with perinatal asphyxia.

Objective: To examine the perceptions and attitudes toward spontaneous adverse drug reaction (ADR) reporting system among community pharmacists and identify factors that influence reporting, by implementing a survey. Methods: A structured questionnaire was developed and distributed online. Request for the survey was posted on the website of pharmacy’s billing program, and the survey was conducted for 8 days. We collected the participants’ response on their work environment, experience of ADR reporting, and their perception and attitude on the reporting system. Multivariate logistic regression was used to evaluate factors influencing ADR reporting. Results: A total of 382 pharmacists participated in the survey. Significant contributing factors for reporting level were age (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.84-0.96), knowledge of reporting method (OR, 53.56; 95% CI, 9.10-315.41), installation of reporting program (OR, 31.92; 95% CI, 4.16-244.75), and encouragement from the Korean pharmaceutical association (OR, 4.13; 95% CI, 1.11-15.35). Regarding the attitude toward spontaneous ADR reporting system, ‘lack of time for reporting’ (OR, 0.29; 95% CI, 0.15-0.53) and ‘complexity of reporting procedure’ (OR, 0.51; 95% CI, 0.31-0.84), were associated with a low likelihood of reporting. Conclusion: Our results indicated that the knowledge of ADR reporting method, installation of the reporting program, and encouragement from the Korean Pharmaceutical Association contribute to active reporting. It is necessary to simplify the reporting method, make the ADR reporting program user-friendly, and provide educational interventions to increase participation in spontaneous reporting by the community pharmacists.

Atorvastatin is one of the most widely prescribed medications for dyslipidemia treatment. In Korea, post combined therapy with ezetimibe, a 73-year-old woman was reported by a community pharmacy to have experienced visual field defect, which recovered after drug discontinuation. She had never experienced this symptom before, and several studies have reported an association between use of statins and visual disorders such as blurred vision, diplopia, and cataract. Blockage of cholesterol accumulation, oxidative stress, or myopathy is expected to be a cause of this symptom. Naranjo scale, Korean causality assessment algorithm (Ver.2), and World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria were the three tools used to determine causality between the visual disorder and atorvastatin. The results represent ‘probable’, ‘certain’, and ‘probable/likely’ causality, respectively. Our results, in combination with a review of literature, indicate that ocular adverse effects are highly likely related to atorvastatin.