Pharmacoepidemiology and Drug Safety最新文献

{"title":"Incidence and Clinical Significance of Drug-Induced Antibodies and Hemolytic Anemia Associated With Beta-Lactam Antibiotics: A Prospective Cohort Study.","authors":"Li Wang, Lixin Wang, Zengzhen Wei, Chunyan Huang, Li Qin, Bin Tan","doi":"10.1002/pds.70259","DOIUrl":"10.1002/pds.70259","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced immune hemolytic anemia (DIIHA), a rare complication of beta-lactams, lacks population-level data on subclinical antibody prevalence.</p><p><strong>Objective: </strong>To quantify drug-induced antibody incidence and hematologic impact in beta-lactam-treated patients.</p><p><strong>Methods: </strong>Prospective cohort of 4040 patients receiving ceftriaxone, piperacillin/trizobactam, piperacillin/sulbactam 2:1 and piperacillin/tazobactam at a Chinese tertiary hospital (2020.1-2020.9). Antibodies were detected via immunoadsorption assays. The primary outcomes were changes in hemoglobin, bilirubin, and lactate dehydrogenase (LDH) levels.</p><p><strong>Results: </strong>Antibody positivity occurred in 18.07% (730/4040), highest with piperacillin/sulbactam 2:1 (24.02% vs. 0.43% Ceftriaxone, p < 0.001). Seropositive patients had a significant hemoglobin decline (Δ = -5.00 g/L, 95% CI -6.2 to -3.8) and bilirubin elevation (Δ = +0.95 μmol/L, 95% CI +0.4 to +1.5), but only 0.2% (2/730) progressed to severe anemia. Subclinical hemolysis (LDH > 250 U/L) was prevalent (89.3%).</p><p><strong>Conclusion: </strong>Beta-lactams exhibit high asymptomatic antibody rates (18.07%) with minimal severe hemolysis risk (0.2%). Protocolized monitoring and HLA screening may optimize safety. This first large-scale prospective cohort quantifies the underrecognized epidemic of subclinical antibody formation, challenging traditional pharmacovigilance frameworks that focus solely on overt hemolysis.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70259"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Data Quality by Proxy: Can We Evaluate All Dimensions of the European Medicines Agency Data Quality Framework for Registry-Based Post-Authorization Safety Studies?","authors":"Pamela Dobay, Meritxell Sabidó","doi":"10.1002/pds.70296","DOIUrl":"10.1002/pds.70296","url":null,"abstract":"<p><strong>Purpose: </strong>An increasing number of studies based on secondary data use, including registry-based studies, have been initiated to address post-authorization regulatory commitments. We map differences across tools used in data quality (DQ) assessments, including those embedded in fitness-for-purpose (FFP) assessments, and describe their strengths and limitations for use in DQ assessments of registries considered for use in post-approval safety studies (PASS). We focus on the use case where marketing authorization holders (MAHs) cannot directly analyze patient-level data. Furthermore, we propose complementary measures to improve DQ assessment, including a set of data quality indicators (DQIs).</p><p><strong>Methods: </strong>We analyzed the extent to which the selected tools used in registry assessments address DQ dimensions and metrics defined in the European Medicines Agency-DQ Framework (EMA-DQF). We specifically considered the use case where DQ assessment was purely based on registry documentation and qualitative due to data access restrictions.</p><p><strong>Results: </strong>None of the tools covered all DQ dimensions and metrics; they had limited utility for evaluating extensiveness (i.e., completeness and coverage), semantic coherence, and reliability (i.e., accuracy and plausibility). Furthermore, some supporting document requirements were more useful than others. For example, the data dictionary is useful for evaluating precision and structural coherence. In contrast, publications have limited utility in DQ assessment.</p><p><strong>Conclusions: </strong>We propose a set of consistent definitions of information requirements and quantitative DQIs that complement existing tools that can be used for evaluating DQ throughout the registry-based PASS lifecycle. If DQIs cannot be evaluated during the preparation of the PASS protocol, uncertainties and their potential impact on the study results need to be acknowledged in the relevant study documents. Additionally, scenario mapping for the removal or replacement of registries with insufficient DQ after PASS initiation is needed.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70296"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12893874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of the Self-Controlled Case Series for Drug Safety Signal Detection: A Multi-Database Study.","authors":"Astrid Coste, Angel Y S Wong, Francois Haguinet, Andrew Bate, Ian J Douglas","doi":"10.1002/pds.70298","DOIUrl":"10.1002/pds.70298","url":null,"abstract":"<p><strong>Background: </strong>Differences in performance of the Self-Controlled Case Series (SCCS) for signal detection have been reported across different databases. However, there has been limited comparative analysis of performance and it remains unknown whether combinations of databases could enable more effective signal detection.</p><p><strong>Objectives: </strong>This study aims to compare the performance of the SCCS for signal detection across several data sources, and to determine whether combinations of databases can improve SCCS performance.</p><p><strong>Methods: </strong>We applied the SCCS to macrolides and fluoroquinolone antibiotics, in four databases: Merative MarketScan Commercial Claims and Medicare, the Clinical Practice Research Datalink (CPRD) Aurum and the Système National des Données de Santé. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. The observation period lasted 2 years, with a 30-day risk-window after each dispensing. Diagnostic performance was measured using sensitivity, specificity and area under the receiver operating curve (AUC) with respect to the product labels, both for individual and combinations of databases.</p><p><strong>Results: </strong>The sensitivity of the SCCS ranged from 0.57-0.89 across individual databases, and the specificity from 0.43-0.77 when limited to drug-outcome pairs sufficiently powered. The combination of all databases achieved the maximum sensitivity of 0.89 (0.41 specificity) for the full reference set, and a sensitivity of 1 (0.35 specificity) for drug outcome pairs with enough power. Whilst AUCs ranged from 0.66 to 0.71 across individual databases, the highest performing combination was CPRD plus MarketScan Commercial Claims (0.76 AUC).</p><p><strong>Conclusions: </strong>Using a carefully designed reference set of drug-outcome pairs well suited to the study design, the SCCS performance varied substantially by database due to differences in population, reporting, healthcare and coding systems and prescribing patterns. Multi-database studies showed increased performance of SCCS for signal detection.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70298"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts from II ISPE LATAM Pharmacoepidemiology Congress, 9-11 October 2025, Sorocaba, Brazil.","authors":"","doi":"10.1002/pds.70309","DOIUrl":"https://doi.org/10.1002/pds.70309","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 Suppl 1 ","pages":"e70309"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing and Research in Medicines Management - PRIMM, 35th Annual Scientific Meeting, Manchester, UK, 12 December 2025, Shaping the Digital Future of Healthcare: Data-Driven Decision-Making.","authors":"","doi":"10.1002/pds.70330","DOIUrl":"https://doi.org/10.1002/pds.70330","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 Suppl 2 ","pages":"e70330"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discontinuation of Renin-Angiotensin System Inhibitors and Risk of End-Stage Renal Disease and Cardiovascular Outcomes Among Patients With Type 2 Diabetes and Chronic Kidney Disease: A Nationwide Taiwanese Cohort Study.","authors":"Yaa-Hui Dong, Chia-Hsuin Chang, Li-Chiu Wu, Sengwee Toh","doi":"10.1002/pds.70323","DOIUrl":"https://doi.org/10.1002/pds.70323","url":null,"abstract":"<p><strong>Purpose: </strong>This nationwide cohort study examined the effects of discontinuation versus continuation of renin-angiotensin system inhibitors (RASis) on major renal and cardiovascular outcomes after the estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m² in patients with type 2 diabetes and treated with RASis.</p><p><strong>Methods: </strong>Using linked Taiwanese databases with claims and clinical data, we identified patients with type 2 diabetes who used RASis during 2016-2020, and either discontinued or continued RASis within 180 days when their eGFR fell below 45 mL/min/1.73 m². The outcomes of interest included end-stage renal disease (ESRD), myocardial infarction, stroke, heart failure, and all-cause mortality. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for RASi discontinuation versus RASi continuation using on-treatment and intention-to-treat analyses and inverse probability weighting to adjust for baseline and time-varying covariates.</p><p><strong>Results: </strong>We identified 251 853 eligible patients, of whom 37 108 (15%) discontinued RASis and 214 745 (85%) continued RASis. The on-treatment HR associated with RASi discontinuation was 2.52 (95% CI, 2.33-2.73) for ESRD, 1.18 (1.08-1.30) for myocardial infarction, 1.28 (1.19-1.37) for stroke, 1.18 (1.13-1.24) for heart failure, and 1.77 (1.70-1.84) for all-cause mortality. Results from the intention-to-treat analysis were similar, albeit more conservative. Findings remained consistent across eGFR strata (≥ 30 to < 45 and < 30 mL/min/1.73 m²), urine albumin-creatinine ratio categories (≥ 300 and < 300 mg/g), and patient subgroups with various baseline characteristics.</p><p><strong>Conclusion: </strong>Our results support continuing RASi treatment even when the eGFR declines to below 45 mL/min/1.73 m² based on potential renal, cardiovascular, and survival benefits.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70323"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ondansetron Use for Women With Hyperemesis Gravidarum and Risks of Spontaneous Abortion and Stillbirth: A Retrospective Cohort Study.","authors":"Jianzhou Yang, Miao Hong, Feng Liang, Yujie Han, Rihua Xie, Daniel Krewski, Donald Mattison, Daniel J Corsi, Mark Walker, Darine El-Chaâr, Doug McNair, Junjie Xu, Shi Wu Wen","doi":"10.1002/pds.70335","DOIUrl":"https://doi.org/10.1002/pds.70335","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ondansetron, a selective 5-hydroxytryptamine type 3 serotonin receptor antagonist, is the most prescribed medication to treat hyperemesis gravidarum in the United States. However, certain characteristics of ondansetron, such as QT interval prolongation and its ability to cross the placenta, may suggest possible fetal harm following maternal exposure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess the association between ondansetron use and risk for spontaneous abortion and stillbirth in pregnant women affected by hyperemesis gravidarum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Retrospective cohort study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Electronic healthcare databases from over 500 healthcare facilities across the United States between 2001 and 2016.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Pregnant women affected by hyperemesis gravidarum are eligible for evaluation of spontaneous abortion and stillbirth, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;The hazard ratios (HRs) and 95% confidence intervals (CIs) for spontaneous abortion and stillbirth were estimated for women exposed to ondansetron versus women not exposed to an antiemetic in a time-dependent manner, using a Cox proportional-hazards regression model. Dose-response relationships between ondansetron use and respective outcomes were assessed, with ondansetron doses categorized as no use, 1-4, 5-15, and ≥ 16 mg. We conducted post hoc analyses to compare the risks of spontaneous abortion and stillbirth among ondansetron users with those exposed to other antiemetics, as well as with those exposed only to the two most frequently used antiemetics, promethazine and metoclopramide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There were 34 273 and 50 862 pregnant women affected by hyperemesis gravidarum, eligible for evaluation of spontaneous abortion and stillbirth, respectively. Following propensity score matching on a 1:1 ratio between women solely exposed to ondansetron and women not exposed to antiemetics, a total of 10 238 and 13 585 pairs were included in the main analysis of spontaneous abortion and stillbirth, respectively. Exposure to ondansetron was associated with a decreased risk for spontaneous abortion compared with women not exposed to an antiemetic (adjusted HR 0.82, 95% CI 0.73, 0.91) under the time-dependent Cox model. There was no significant dose-dependent relationship between spontaneous abortion and ondansetron exposure. There was no association between ondansetron exposure and stillbirth. The adjusted HR for stillbirth with time-dependent defined exposure was 1.34 (95% CI 0.87-2.08) in mild cases and 0.72 (95% CI 0.23-2.26) in severe cases. A reduction in spontaneous abortion risk with ondansetron users compared to other antiemetic users was also observed (aHR 0.85, 95% CI 0.73-0.98).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Obstetric use of ondansetron suggested a decreased risk of spontaneous abortion, with no increased risk of stillbirth among pregnant women affecte","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70335"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Indapamide Prolonged-Release and Perindopril Versus Perindopril Monotherapy for Treated Uncontrolled Hypertension: A Target Trial Emulation.","authors":"Céline Darricarrere, Virginie Simon, Manel Pladevall-Vila, Emmanuelle Jacquot, Morgane Ballon, Marie Mangin, Dominique Procureur, Jaume Aguado, Xabier Garcia-Albeniz","doi":"10.1002/pds.70295","DOIUrl":"10.1002/pds.70295","url":null,"abstract":"<p><strong>Objective: </strong>To assess the effectiveness of indapamide prolonged release and perindopril in combination using blood pressure (BP) records collected in routine practice.</p><p><strong>Methods: </strong>Using a target trial emulation framework, an observational retrospective cohort study was conducted. The data source was the United Kingdom's CPRD Aurum general practice database. Adults with systolic BP (SBP) ≥ 145 mmHg treated with perindopril 4/5 mg for ≥ 4 weeks at a stable dose who either added indapamide 1.5 mg to perindopril (n = 193) or continued on perindopril monotherapy (n = 14 571) were included. Balance between treatment arms was achieved with propensity score matching; results were explored in additional analyses using different eligibility criteria and alternative statistical methodologies. The primary outcome was change in SBP from baseline to Week 8 between indapamide added to perindopril versus perindopril monotherapy.</p><p><strong>Results: </strong>In the primary analysis, indapamide added to perindopril yielded an additional SBP reduction of -6.3 mmHg (95% confidence interval [CI] -8.7 to -3.9) over perindopril monotherapy at Week 8. Results of additional analyses were consistent with the main analysis, but effect estimates varied due to diverse underlying assumptions.</p><p><strong>Conclusions: </strong>Target trial emulation allowed assessment of antihypertensive treatment effectiveness, and indapamide plus perindopril yielded clinically meaningful decreases in SBP over perindopril monotherapy. Secondary and sensitivity analyses support that these findings were robust.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70295"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychotropic Use Among Classroom Teachers in Espírito Santo: A Cross-Sectional Study.","authors":"Yohan Cancilheri Mazzini, Paulo Vitor Ramos Vitori, Kimberly Domingos Schneider, Gustavo Magno Baldin Tiguman, Kérilin Stancine Santos Rocha, Dyego Carlos Souza Anacleto de Araújo","doi":"10.1002/pds.70327","DOIUrl":"10.1002/pds.70327","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the prevalence of psychotropic use among classroom teachers and to identify associated factors.</p><p><strong>Methods: </strong>A cross-sectional study was conducted between January and February 2024 in Espírito Santo, Brazil. The study included teachers from 20 state schools selected through probabilistic sampling. Data were collected in person using a self-administered questionnaire that addressed sociodemographic characteristics, working conditions, mental health history, mental health screening scales, and the use of psychotropic medications. Poisson regression with robust variance was employed to estimate the prevalence ratio of psychotropic and antidepressant use. The study was approved by the research ethics committee.</p><p><strong>Results: </strong>The study included 453 teachers. The prevalence of psychotropic medication use was 20.0% (95% CI: 16.9%-22.9%), while the prevalence of antidepressant use was 16.9% (95% CI: 13.8%-19.8%). In the multivariate analysis, a higher prevalence of psychotropic use was observed among cisgender women (PR = 1.91; 95% CI: 1.07-3.39) and teachers with depressive symptoms (PR = 2.30; 95% CI: 1.26-4.22). Antidepressant use was also more frequent among cisgender women (PR = 2.07; 95% CI: 1.12-3.85) and those with depressive symptoms (PR = 2.01; 95% CI: 1.05-3.82), while teachers working in schools located in Santa Teresa showed a lower prevalence compared to those in Vitória (PR = 0.31; 95% CI: 0.10-0.90).</p><p><strong>Conclusion: </strong>The findings indicate a considerable prevalence of psychotropic and antidepressant use among teachers, particularly among cisgender women and those presenting depressive symptoms.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70327"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Different As-Treated Approaches: A Methodological Study Using Real-World Data on Psoriasis Treatments.","authors":"Sejun Kim, Andreas Jensen, Alexander Egeberg, Lone Graff Stensballe","doi":"10.1002/pds.70337","DOIUrl":"10.1002/pds.70337","url":null,"abstract":"<p><strong>Background: </strong>Accurate pharmaco-epidemiological assessment of the safety of biological treatments is essential but methodologically challenging.</p><p><strong>Aims: </strong>This study evaluated how different assumptions regarding treatment switching and treatment episode definitions affect outcome estimates in psoriasis patients, focusing on malignancies and serious infections.</p><p><strong>Methods: </strong>Data from Danish national registers (2009-2022) were analyzed for hospitalized psoriasis patients treated with ustekinumab, non-biologics, tumor necrosis factor-α inhibitors, and other interleukin inhibitors excluding ustekinumab. Various as-treated approaches were assessed and compared to the Intention-to-Treat (ITT) approach. The as-treated approaches included: (1) RC-switch, considering switching only between ustekinumab and the comparator in question, (2) Bio-switch, considering switches among all biologics, (3) Multi-switch, analyzing all groups simultaneously, and (4) Hierarchy-switch, analyzing switching by a predefined hierarchy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using Cox models. Sensitivity analyses incorporated treatment episodes based on the defined daily dose (DDD) and grace periods.</p><p><strong>Results: </strong>Broader treatment switching allowances affected outcome estimates. For malignancies, the Bio-switch approach yielded the largest HR changes relative to the ITT. For serious infections, also, Bio-switch produced the largest HR shifts, for example, HR 1.32 (CI 1.09, 1.58) versus ITT HR 1.08 (CI 0.91, 1.29). Sensitivity analyses showed that accounting for episode gaps influenced HRs and widened CIs.</p><p><strong>Conclusion: </strong>The number of events within the exposure group varied by approaches, influencing the HR estimates. The multi-switch approach effectively captured treatment switching and reduced statistical uncertainty, supporting clearer safety conclusions. Tracking each treatment period with gaps reflects real-world practice but may lower statistical power and should be carefully considered in analyses.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 2","pages":"e70337"},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}