Academic Journal
Active and Non-Active Comparators Yield Different Estimates of the Association Between Proton Pump Inhibitor Use and Recorded Mortality During Immune Checkpoint Inhibitor Therapy for Advanced Non-Small Cell Lung Cancer.
| Τίτλος: | Active and Non-Active Comparators Yield Different Estimates of the Association Between Proton Pump Inhibitor Use and Recorded Mortality During Immune Checkpoint Inhibitor Therapy for Advanced Non-Small Cell Lung Cancer. |
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| Συγγραφείς: | Ihara Y; Clinical Research Promotion Unit, Clinical Therapeutic Trial Center, Ehime University Hospital, Toon, Ehime, Japan.; Center for Data Science, Ehime University, Matsuyama, Ehime, Japan.; Integrated Medical and Agricultural School of Public Health, Ehime University, Toon, Ehime, Japan., Okada N; Pharmacy Department, Yamaguchi University Hospital, Ube, Yamaguchi, Japan., Mizutani M; Department of Respiratory Medicine, Yodogawa Christian Hospital, Osaka, Japan., Nakamura Y; Department of Cardiology, Pulmonology, Hypertension & Nephrology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan., Shimomura Y; Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan., Yamamoto S; Department of Respiratory Medicine, Yodogawa Christian Hospital, Osaka, Japan.; Department of Clinical Oncology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. |
| Πηγή: | Pharmacoepidemiology and drug safety [Pharmacoepidemiol Drug Saf] 2026 Sep; Vol. 35 (9), pp. e70478. |
| Τύπος έκδοσης: | Journal Article; Comparative Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley Country of Publication: England NLM ID: 9208369 Publication Model: Print Cited Medium: Internet ISSN: 1099-1557 (Electronic) Linking ISSN: 10538569 NLM ISO Abbreviation: Pharmacoepidemiol Drug Saf Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chichester, West Sussex : Wiley, 1992- |
| Ιατρικοί όροι (MeSH): | Proton Pump Inhibitors*/adverse effects , Proton Pump Inhibitors*/administration & dosage , Proton Pump Inhibitors*/therapeutic use , Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/mortality , Carcinoma, Non-Small-Cell Lung*/pathology , Lung Neoplasms*/drug therapy , Lung Neoplasms*/mortality , Lung Neoplasms*/pathology , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/administration & dosage, Japan/epidemiology ; Histamine H2 Antagonists/administration & dosage ; Histamine H2 Antagonists/adverse effects ; Histamine H2 Antagonists/therapeutic use ; Databases, Factual/statistics & numerical data ; Humans ; Female ; Retrospective Studies ; Male ; Aged ; Middle Aged ; Aged, 80 and over ; Proportional Hazards Models ; Propensity Score ; Cohort Studies |
| Περίληψη: | Purpose: 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-users, which may differ in their underlying need for acid-suppressive therapy. We evaluated the association between PPI use and mortality using histamine-2 receptor antagonist (H2RA) users as an active comparator among patients with advanced non-small cell lung cancer (NSCLC) receiving ICIs. Methods: We conducted a retrospective cohort study using a Japanese administrative claims database. Patients with advanced NSCLC who initiated first-line ICI-based therapy and received either a PPI or an H2RA within 30 days before or on the day of ICI initiation were included. The index date was defined as the initiation date of the first-line ICI-based regimen. The primary outcome was all-cause mortality within 3 years. 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). Results: 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, 0.93-1.20). In contrast, PPI users had higher mortality than patients receiving neither PPIs nor H2RAs (HR, 1.13; 95% CI, 1.05-1.20). Conclusion: 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. (© 2026 John Wiley & Sons Ltd.) |
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| Contributed Indexing: | Keywords: histamine‐2 receptor antagonist; immune checkpoint inhibitor; mortality; non‐small cell lung cancer; overlap weighting; pharmacoepidemiology; proton pump inhibitor Local Abstract: [plain-language-summary] Proton pump inhibitors and histamine‐2 receptor antagonists are both used to reduce stomach acid. Proton pump inhibitors are commonly prescribed to patients with cancer, but they may alter the gut microbiome, which could influence the effectiveness of immune checkpoint inhibitors used to treat advanced non‐small cell lung cancer. Many previous studies compared proton pump inhibitor users with patients who did not use proton pump inhibitors. However, the choice of comparison group may affect the estimated association because patients who receive acid‐suppressive therapy may differ from non‐users in their underlying conditions, gastrointestinal symptoms, medication use, and clinical status. To address this issue, we compared proton pump inhibitor users with histamine‐2 receptor antagonist users as an active comparator, because both groups received acid‐suppressive therapy for overlapping indications. Using a large Japanese real‐world database, we found no clear difference in recorded mortality between proton pump inhibitor and histamine‐2 receptor antagonist users receiving immune checkpoint inhibitor–based therapy. In contrast, proton pump inhibitor use was associated with higher recorded mortality when compared with patients receiving neither proton pump inhibitors nor histamine‐2 receptor antagonists. These findings highlight the importance of selecting an appropriate comparison group when evaluating the association between proton pump inhibitor use and outcomes during immune checkpoint inhibitor therapy. |
| Substance Nomenclature: | 0 (Proton Pump Inhibitors) 0 (Immune Checkpoint Inhibitors) 0 (Histamine H2 Antagonists) |
| Entry Date(s): | Date Created: 20260914 Date Completed: 20260914 Latest Revision: 20260917 |
| Update Code: | 20260917 |
| PubMed Central ID: | PMC13574716 |
| DOI: | 10.1002/pds.70478 |
| PMID: | 42736173 |
| Βάση Δεδομένων: | MEDLINE |
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