Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS)
Background: Immunosuppression by biologic response modifiers (BRM) is a crucial component for successfulorgan transplantation. In addition to their variable effectiveness in the prevention of organ rejection,these medications have safety concerns that complicate therapeutic outcomes in organ transpl...
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| Format: | Article |
| Language: | English |
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Shiraz University of Medical Sciences
2013-04-01
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| Series: | International Journal of Organ Transplantation Medicine |
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| Online Access: | http://home.sums.ac.ir/~habibzaf/ojs/index.php/IJOTM/article/view/148/276 |
| _version_ | 1819267893551955968 |
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| author | A. K. Ali |
| author_facet | A. K. Ali |
| author_sort | A. K. Ali |
| collection | DOAJ |
| description | Background: Immunosuppression by biologic response modifiers (BRM) is a crucial component for successfulorgan transplantation. In addition to their variable effectiveness in the prevention of organ rejection,these medications have safety concerns that complicate therapeutic outcomes in organ transplantpatients.Objective: This study aims at identifying and characterizing safety signals of serious adverse events associatedwith exposure to BRM among organ transplant patients in a real-world environment.Methods: The FDA Adverse Event Reporting System was utilized to apply a pharmacovigilance disproportionalityanalysis to indentify serious adverse events. Associations between drugs and events weremeasured by empirical Bayes geometric mean (EBGM) and the corresponding 95% confidence intervals(EB05–EB95). Associations with EBGM≥2 were considered significant safety signals.Results: From 1997 to 2012, a total of 12,151 serious adverse event reports for BRM were reported; 15.6%of them (n=1,711) met the safety signal threshold of EB05>1, and 11.6% of these signals (n=199) weresignificant (EBGM≥2). Sirolimus and mycophenolate accounted for the majority of all signals; antithymocyteimmunoglobulin (ATI) and cyclosporine contributed to the majority of significant signals. The followingsignificant signals were identified for ATI (reduced therapeutic response, pulmonary edema, hypotension,serum sickness, infusion-related reaction, and anaphylactic reaction); for azathioprine (alternariainfection, fungal skin infection, and lymphoproliferative disorder); for cyclosporine (neurotoxicity,graft vs. host disease, and thyroid cancer); for cyclophosphamide (disease progression); for daclizumab(cytomegalovirus infection); and for tacrolimus (coma and tremor). 33.6% of these events contributedto patient death (n=67); 6.5% were life-threatening (n=13); 32.1% lead to hospitalization (n=64); and27.6% resulted in other serious outcomes (n=55).Conclusion: Utilization of BRM for the prophylaxis against transplant rejection is associated with seriousadverse events that could be fatal. |
| first_indexed | 2024-12-23T21:24:24Z |
| format | Article |
| id | doaj.art-1d0cf4f4eca64ef1bc97695405e5f88e |
| institution | Directory Open Access Journal |
| issn | 2008-6490 2008-6482 |
| language | English |
| last_indexed | 2024-12-23T21:24:24Z |
| publishDate | 2013-04-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | International Journal of Organ Transplantation Medicine |
| spelling | doaj.art-1d0cf4f4eca64ef1bc97695405e5f88e2022-12-21T17:30:38ZengShiraz University of Medical SciencesInternational Journal of Organ Transplantation Medicine2008-64902008-64822013-04-01426271Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS)A. K. AliBackground: Immunosuppression by biologic response modifiers (BRM) is a crucial component for successfulorgan transplantation. In addition to their variable effectiveness in the prevention of organ rejection,these medications have safety concerns that complicate therapeutic outcomes in organ transplantpatients.Objective: This study aims at identifying and characterizing safety signals of serious adverse events associatedwith exposure to BRM among organ transplant patients in a real-world environment.Methods: The FDA Adverse Event Reporting System was utilized to apply a pharmacovigilance disproportionalityanalysis to indentify serious adverse events. Associations between drugs and events weremeasured by empirical Bayes geometric mean (EBGM) and the corresponding 95% confidence intervals(EB05–EB95). Associations with EBGM≥2 were considered significant safety signals.Results: From 1997 to 2012, a total of 12,151 serious adverse event reports for BRM were reported; 15.6%of them (n=1,711) met the safety signal threshold of EB05>1, and 11.6% of these signals (n=199) weresignificant (EBGM≥2). Sirolimus and mycophenolate accounted for the majority of all signals; antithymocyteimmunoglobulin (ATI) and cyclosporine contributed to the majority of significant signals. The followingsignificant signals were identified for ATI (reduced therapeutic response, pulmonary edema, hypotension,serum sickness, infusion-related reaction, and anaphylactic reaction); for azathioprine (alternariainfection, fungal skin infection, and lymphoproliferative disorder); for cyclosporine (neurotoxicity,graft vs. host disease, and thyroid cancer); for cyclophosphamide (disease progression); for daclizumab(cytomegalovirus infection); and for tacrolimus (coma and tremor). 33.6% of these events contributedto patient death (n=67); 6.5% were life-threatening (n=13); 32.1% lead to hospitalization (n=64); and27.6% resulted in other serious outcomes (n=55).Conclusion: Utilization of BRM for the prophylaxis against transplant rejection is associated with seriousadverse events that could be fatal.http://home.sums.ac.ir/~habibzaf/ojs/index.php/IJOTM/article/view/148/276Immunosuppressive medicationsBiologic response modifiersPharmacovigilanceSerious adverse eventsFAERS |
| spellingShingle | A. K. Ali Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) International Journal of Organ Transplantation Medicine Immunosuppressive medications Biologic response modifiers Pharmacovigilance Serious adverse events FAERS |
| title | Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) |
| title_full | Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) |
| title_fullStr | Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) |
| title_full_unstemmed | Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) |
| title_short | Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS) |
| title_sort | pharmacovigilance analysis of serious adverse events reported for biologic response modifiers used as prophylaxis against transplant rejection a real world postmarketing experience from the us fda adverse event reporting system faers |
| topic | Immunosuppressive medications Biologic response modifiers Pharmacovigilance Serious adverse events FAERS |
| url | http://home.sums.ac.ir/~habibzaf/ojs/index.php/IJOTM/article/view/148/276 |
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