{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:43:30Z","timestamp":1773254610847,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate pharmaco\u2010epidemiological assessment of the safety of biological treatments is essential but methodologically challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from Danish national registers (2009\u20132022) were analyzed for hospitalized psoriasis patients treated with ustekinumab, non\u2010biologics, tumor necrosis factor\u2010\u03b1 inhibitors, and other interleukin inhibitors excluding ustekinumab. Various\n                      <jats:italic>as\u2010treated<\/jats:italic>\n                      approaches were assessed and compared to the\n                      <jats:italic>Intention\u2010to\u2010Treat<\/jats:italic>\n                      (ITT) approach. The\n                      <jats:italic>as\u2010treated<\/jats:italic>\n                      approaches included: (1) RC\u2010switch, considering switching only between ustekinumab and the comparator in question, (2) Bio\u2010switch, considering switches among all biologics, (3) Multi\u2010switch, analyzing all groups simultaneously, and (4) Hierarchy\u2010switch, 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Broader treatment switching allowances affected outcome estimates. For malignancies, the Bio\u2010switch approach yielded the largest HR changes relative to the ITT. For serious infections, also, Bio\u2010switch 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The number of events within the exposure group varied by approaches, influencing the HR estimates. The multi\u2010switch approach effectively captured treatment switching and reduced statistical uncertainty, supporting clearer safety conclusions. Tracking each treatment period with gaps reflects real\u2010world practice but may lower statistical power and should be carefully considered in analyses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70337","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:56:01Z","timestamp":1769687761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparing Different\n                    <scp>\n                      <i>As\u2010Treated<\/i>\n                    <\/scp>\n                    Approaches: A Methodological Study Using Real\u2010World Data on Psoriasis Treatments"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-4685","authenticated-orcid":false,"given":"Sejun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Children and Adolescent Medicine Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"},{"name":"Mary's Data Powerhouse, Mary Elizabeth's Hospital, Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Children and Adolescent Medicine Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"},{"name":"Mary's Data Powerhouse, Mary Elizabeth's Hospital, Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Egeberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Dermatology Bispebjerg Hospital, University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lone Graff","family":"Stensballe","sequence":"additional","affiliation":[{"name":"Department of Children and Adolescent Medicine Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"},{"name":"Mary's Data Powerhouse, Mary Elizabeth's Hospital, Danish National University Hospital \u201cRigshospitalet\u201d  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research (CBER) Center for Drug Evaluation and Research (CDER) \u201cE9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials \u201d(2021)."},{"key":"e_1_2_10_3_1","unstructured":"Committee for Medicinal Products for Human Use \u201cICH E9 (R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials \u201d(2020)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7033"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441\u2010019\u201000061\u2010x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1986"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2021.106494"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.421"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2023.2200870"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.2158"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2023.2259829"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1917"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4097\/kja.23278"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.025561"},{"key":"e_1_2_10_15_1","volume-title":"Causal Inference: What If","author":"Hernan M. 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