PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database
BackgroundTransplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| author | Alexandre O. Gérard Alexandre O. Gérard Alexandre O. Gérard Diane Merino Diane Merino Jonathan Benzaquen Alexandre Destere Delphine Borchiellini Clément Gosset Clément Gosset Fanny Rocher Marine Andreani Charles-Hugo Marquette Henri Montaudié Henri Montaudié Milou-Daniel Drici Antoine Sicard Antoine Sicard |
| author_facet | Alexandre O. Gérard Alexandre O. Gérard Alexandre O. Gérard Diane Merino Diane Merino Jonathan Benzaquen Alexandre Destere Delphine Borchiellini Clément Gosset Clément Gosset Fanny Rocher Marine Andreani Charles-Hugo Marquette Henri Montaudié Henri Montaudié Milou-Daniel Drici Antoine Sicard Antoine Sicard |
| author_sort | Alexandre O. Gérard |
| collection | DOAJ |
| description | BackgroundTransplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of AR between the different ICI classes remains to be defined.MethodsVigiBase® (WHO’s pharmacovigilance database) was queried for reports of AR involving CTLA4, PD1, or PDL1 inhibitors. Disproportionality analysis compares the proportion of reports with a specific adverse drug reaction (ADR) and a given drug to the proportion of reports with the same ADR and other drugs. A lower 95% confidence interval for the Information Component (IC) >0 suggests a signal. The comparative Reporting Odds Ratios (ROR) for AR, between PD1 and PDL1 inhibitors, was calculated.ResultsWe gathered 159 AR involving an ICI, especially nivolumab (73, 45.9%), mostly affecting kidneys (87, 54.7%). Median time to onset: 28 days. Fatal outcome: 36 reports (22.6%). ICI were significantly associated with AR: IC=1.7 [1.4;1.9]. Specifically, PD1 inhibitors yielded an IC of 2.0 [1.7;2.2] (152 reports observed compared to 38 expected). By contrast, the IC of PDL1 inhibitors was negative: -2.6 [-6.4;-1.0] (1 observed, 9 expected). The comparative ROR of PD1 compared to PDL1 inhibitors was 33.7 [4.7;240.9] (p=0.0005).ConclusionsWe confirm the association between ICI treatment and AR. Notably, PDL1 inhibitors showed surprisingly low AR reports compared to CTLA4 and PD1 inhibitors. Further prospective studies are warranted to confirm whether PDL1 inhibitors indeed reduce AR risk compared to other ICI. |
| format | Article |
| id | doaj-art-9b86a08bb70c4c4a87079d43d2b8d560 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-9b86a08bb70c4c4a87079d43d2b8d5602025-01-22T07:11:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15140331514033PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance databaseAlexandre O. Gérard0Alexandre O. Gérard1Alexandre O. Gérard2Diane Merino3Diane Merino4Jonathan Benzaquen5Alexandre Destere6Delphine Borchiellini7Clément Gosset8Clément Gosset9Fanny Rocher10Marine Andreani11Charles-Hugo Marquette12Henri Montaudié13Henri Montaudié14Milou-Daniel Drici15Antoine Sicard16Antoine Sicard17Department of Nephrology-Dialysis-Transplantation, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceDepartment of Clinical Pharmacology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceLaboratory of Molecular Physio Medicine (LP2M), UMR 7370, CNRS, University Côte d’Azur, Nice, FranceDepartment of Clinical Pharmacology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceMolecular and Cellular Pharmacology Institute (IPMC), UMR 7275, CNRS, Université Côte d’Azur, Nice, FranceMolecular and Cellular Pharmacology Q6 Institute (IPMC), UMR 7275, CNRS, Université Côte d'Azur, Nice, FranceDepartment of Clinical Pharmacology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceDepartment of Clinical Research and Innovation, Department of Medical Oncology, Centre Antoine Lacassagne, Nice, FranceDepartment of Nephrology-Dialysis-Transplantation, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceLaboratory of Molecular Physio Medicine (LP2M), UMR 7370, CNRS, University Côte d’Azur, Nice, FranceDepartment of Clinical Pharmacology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceDepartment of Nephrology-Dialysis-Transplantation, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceMolecular and Cellular Pharmacology Q6 Institute (IPMC), UMR 7275, CNRS, Université Côte d'Azur, Nice, FranceDepartment of Dermatology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceMediterranean Center for Molecular Medicine (C3M), UMR 1065, INSERM, Université Côte d’Azur, Nice, FranceDepartment of Clinical Pharmacology, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceDepartment of Nephrology-Dialysis-Transplantation, Université Côte d’Azur, University Hospital Centre of Nice, Nice, FranceLaboratory of Molecular Physio Medicine (LP2M), UMR 7370, CNRS, University Côte d’Azur, Nice, FranceBackgroundTransplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of AR between the different ICI classes remains to be defined.MethodsVigiBase® (WHO’s pharmacovigilance database) was queried for reports of AR involving CTLA4, PD1, or PDL1 inhibitors. Disproportionality analysis compares the proportion of reports with a specific adverse drug reaction (ADR) and a given drug to the proportion of reports with the same ADR and other drugs. A lower 95% confidence interval for the Information Component (IC) >0 suggests a signal. The comparative Reporting Odds Ratios (ROR) for AR, between PD1 and PDL1 inhibitors, was calculated.ResultsWe gathered 159 AR involving an ICI, especially nivolumab (73, 45.9%), mostly affecting kidneys (87, 54.7%). Median time to onset: 28 days. Fatal outcome: 36 reports (22.6%). ICI were significantly associated with AR: IC=1.7 [1.4;1.9]. Specifically, PD1 inhibitors yielded an IC of 2.0 [1.7;2.2] (152 reports observed compared to 38 expected). By contrast, the IC of PDL1 inhibitors was negative: -2.6 [-6.4;-1.0] (1 observed, 9 expected). The comparative ROR of PD1 compared to PDL1 inhibitors was 33.7 [4.7;240.9] (p=0.0005).ConclusionsWe confirm the association between ICI treatment and AR. Notably, PDL1 inhibitors showed surprisingly low AR reports compared to CTLA4 and PD1 inhibitors. Further prospective studies are warranted to confirm whether PDL1 inhibitors indeed reduce AR risk compared to other ICI.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514033/fullimmune checkpoint inhibitorsallograft rejectiontransplantationpharmacovigilanceoncology |
| spellingShingle | Alexandre O. Gérard Alexandre O. Gérard Alexandre O. Gérard Diane Merino Diane Merino Jonathan Benzaquen Alexandre Destere Delphine Borchiellini Clément Gosset Clément Gosset Fanny Rocher Marine Andreani Charles-Hugo Marquette Henri Montaudié Henri Montaudié Milou-Daniel Drici Antoine Sicard Antoine Sicard PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database Frontiers in Immunology immune checkpoint inhibitors allograft rejection transplantation pharmacovigilance oncology |
| title | PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database |
| title_full | PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database |
| title_fullStr | PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database |
| title_full_unstemmed | PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database |
| title_short | PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database |
| title_sort | pdl1 inhibitors may be associated with a lower risk of allograft rejection than pd1 and ctla4 inhibitors analysis of the who pharmacovigilance database |
| topic | immune checkpoint inhibitors allograft rejection transplantation pharmacovigilance oncology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514033/full |
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