Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis.

OBJECTIVES: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA). METHODS: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs. RESULTS: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs. CONCLUSION: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.

Medications influencing the risk of fall-related injuries in older adults: case-control and case-crossover design studies.

BACKGROUND: Medications influencing the risk of fall-related injuries (FRIs) in older adults have been inconsistent in previous guidelines. This study employed case-control design to assess the association between FRIs and medications, and an additional case-crossover design was conducted to examine the consistency of the associations and the transient effects of the medications on FRIs. METHODS: This study was conducted using a national claims database (2002-2015) in Korea. Older adults (≥ 65 years) who had their first FRI between 2007 and 2015 were matched with non-cases in 1:2 ratio. Drug exposure was examined for 60 days prior to the date of the first FRI (index date) in the case-control design. The hazard period (1-60 days) and two control periods (121-180 and 181-240 days prior to the index date) were investigated in the case-crossover design. The risk of FRIs with 32 medications was examined using conditional logistic regression after adjusting for other medications that were significant in the univariate analysis. In the case-crossover study, the same conditional model was applied. RESULTS: In the case-control design, the five medications associated with the highest risk of FRIs were muscle relaxants (adjusted odd ratio(AOR) = 1.35, 95% confidence interval (CI) = 1.31-1.39), anti-Parkinson agents (AOR = 1.30, 95%CI = 1.19-1.40), opioids (AOR = 1.23, 95%CI = 1.19-1.27), antiepileptics (AOR = 1.19, 95%CI = 1.12-1.26), and antipsychotics (AOR = 1.16, 95%CI = 1.06-1.27). In the case-crossover design, the five medications associated with the highest risk of FRIs were angiotensin II antagonists (AOR = 1.87, 95%CI = 1.77-1.97), antipsychotics (AOR = 1.63, 95%CI = 1.42-1.83), anti-Parkinson agents (AOR = 1.58, 95%CI = 1.32-1.85), muscle relaxants (AOR = 1.42, 95%CI = 1.35-1.48), and opioids (AOR = 1.35, 95%CI = 1.30-1.39). CONCLUSIONS: Anti-Parkinson agents, opioids, antiepileptics, antipsychotics, antidepressants, hypnotics and sedatives, anxiolytics, muscle relaxants, and NSAIDs/antirheumatic agents increased the risk of FRIs in both designs among older adults. Medications with a significant risk only in the case-crossover analysis, such as antithrombotic agents, calcium channel blockers, angiotensin II antagonists, lipid modifying agents, and benign prostatic hypertrophy agents, may have transient effects on FRIs at the time of initiation. Corticosteroids, which were only associated with risk of FRIs in the case-control analysis, had more of cumulative than transient effects on FRIs.

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study.

Previous studies have reported a higher risk of falls among tricyclic antidepressant (TCA) users compared to selective serotonin reuptake inhibitor (SSRI) users, yet SSRIs are known as a safer antidepressant class for use in older adults. This study examined the effects of antidepressant use on the risk of fall-related injuries after classifying antidepressant drugs, polypharmacy, and central nervous system (CNS) drugs by therapeutic classes and identifying factors influencing risk of fall-related injuries. A retrospective matched cohort study based on propensity scores was conducted among older adults, aged 70-89 years, who initiated antidepressant use between 1 January 2012 and 31 December 2014 using the national health insurance system senior cohort in Korea. The proportional hazard Cox regression model was used to examine the association between fall-related injuries and antidepressants. The subgroup analyses were performed to assess the risk of fall-related injuries by the number of concurrently administered medications, therapeutic classes of antidepressants, and CNS class medications. This study found that duloxetine, escitalopram, paroxetine, amitriptyline, imipramine, and trazodone significantly increased the risk of fall-related injuries in older adults. When antidepressants were prescribed to older adults, prescribers carefully considered factors including the dose, number of concurrently administered medications, and therapeutic classes of CNS.

Budget Impact of Switching to Biosimilar Trastuzumab (CT-P6) for the Treatment of Breast Cancer and Gastric Cancer in 28 European Countries.

BACKGROUND: As the economic burden of treating cancer patients has been soaring in European countries, performing a budget impact analysis is becoming one of the requirements for payers' application dossiers. OBJECTIVE: The objective of this study was to estimate the budgetary impact of introducing the biosimilar trastuzumab (CT-P6) from the payer's perspective and to determine the number of additional patients who could be treated with resulting savings in 28 European countries. METHODS: A budget impact model was developed to analyze the financial impact of switching from originator trastuzumab to biosimilar CT-P6 in the treatment of early and metastatic breast cancer and metastatic gastric cancer with a time horizon of 1-5 years. Budgetary savings and the number of patients potentially affected were measured based on epidemiological and sales volume data. The base-case analysis assumed that the price of CT-P6 is 70% of the originator price, the switching rate of originator to CT-P6 in the first year is 20%, and the annual growth in the switching rate for each subsequent year is 5%. RESULTS: For analyses using the base-case scenario following CT-P6 introduction, the total estimated budgetary savings over a 5-year period (depending on the scenario) ranged from €1.13 billion to €2.27 billion based on epidemiological data, or from €0.91 billion to €1.82 billion based on sales volume data. In the first year only, the projected budgetary savings ranged from €58 million to €136 million, and the number of additional patients who could be treated using the savings ranged from 3503 to 7078 by sensitivity analysis. CONCLUSIONS: The conducted budget impact analysis assessing a switch from originator trastuzumab to biosimilar CT-P6 in 28 European countries indicates that budget savings could be between €0.91 billion and €2.27 billion over the next 5 years. These savings could be used to help improve patient access to local biologics in their respective countries while simultaneously strengthening the overall public health landscape across the European Union.