{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:03:25Z","timestamp":1789949005743,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Proton pump inhibitor (PPI) use has been associated with poorer outcomes in patients receiving immune checkpoint inhibitors (ICIs), but most previous studies have compared PPI users with non\u2010users, which may differ in their underlying need for acid\u2010suppressive therapy. We evaluated the association between PPI use and mortality using histamine\u20102 receptor antagonist (H2RA) users as an active comparator among patients with advanced non\u2010small cell lung cancer (NSCLC) receiving ICIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using a Japanese administrative claims database. Patients with advanced NSCLC who initiated first\u2010line ICI\u2010based therapy and received either a PPI or an H2RA within 30\u2009days before or on the day of ICI initiation were included. The index date was defined as the initiation date of the first\u2010line ICI\u2010based regimen. The primary outcome was all\u2010cause mortality within 3\u2009years. Propensity score overlap weighting was used to balance baseline characteristics, and weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 6360 eligible patients, 5409 received conventional PPIs and 951 received H2RAs. After overlap weighting, mortality did not clearly differ between PPI and H2RA users (HR, 1.06; 95% CI, 0.93\u20131.20). In contrast, PPI users had higher mortality than patients receiving neither PPIs nor H2RAs (HR, 1.13; 95% CI, 1.05\u20131.20).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PPI use was not clearly associated with higher mortality when H2RA users were used as an active comparator, whereas a higher mortality estimate was observed when PPI users were compared with patients receiving neither PPI nor H2RA therapy. These findings highlight the importance of comparator selection in observational studies evaluating PPI use during ICI therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70478","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:13:59Z","timestamp":1789438439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Active and Non\u2010Active Comparators Yield Different Estimates of the Association Between Proton Pump Inhibitor Use and Recorded Mortality During Immune Checkpoint Inhibitor Therapy for Advanced Non\u2013Small Cell Lung Cancer"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2538-6328","authenticated-orcid":false,"given":"Yasutaka","family":"Ihara","sequence":"first","affiliation":[{"name":"Clinical Research Promotion Unit, Clinical Therapeutic Trial Center Ehime University Hospital  Toon Ehime Japan"},{"name":"Center for Data Science Ehime University  Matsuyama Ehime Japan"},{"name":"Integrated Medical and Agricultural School of Public Health Ehime University  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-9191","authenticated-orcid":false,"given":"Naoto","family":"Okada","sequence":"additional","affiliation":[{"name":"Pharmacy Department Yamaguchi University Hospital  Ube Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Yodogawa Christian Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, Hypertension &amp; Nephrology, Graduate School of Medicine Ehime University  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Center Kobe University Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9080-4747","authenticated-orcid":false,"given":"Shoichiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Yodogawa Christian Hospital  Osaka Japan"},{"name":"Department of Clinical Oncology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00174"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716948"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910231"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan3706"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4236"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3290"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102015\u2010310376"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014177\u2010z"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.01.006"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010001361"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102021\u2010002421"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010021\u201001606\u20104"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.22915"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061404"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1070076"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.04.047"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.117"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5407"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.12.247"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2016.1260466"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.7819"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40801\u2010022\u201000296\u20105"},{"issue":"4","key":"e_1_2_13_26_1","first-page":"279","article-title":"DRG\/PPS and DPC\/PDPS as Prospective Payment Systems","volume":"55","author":"Ishii M.","year":"2012","journal-title":"Japan Medical Association Journal"},{"key":"e_1_2_13_27_1","unstructured":"Medical Data Vision Co. 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