Tacrolimus(Tac)is a cornerstone immunosuppressant in the treatment regimens for organ transplant recipients.However,its extensive clinical use has brought attention to its associated drug safety concerns.Recent case r...Tacrolimus(Tac)is a cornerstone immunosuppressant in the treatment regimens for organ transplant recipients.However,its extensive clinical use has brought attention to its associated drug safety concerns.Recent case reports highlighting Tac-induced gastrointestinal ulcers have prompted further investigation.In the present study,we analyzed Tac-associated adverse events using data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)to identify potential adverse event signals.Adverse event reports were collected up to the third quarter(Q3)of 2023,revealing 339 cases of Tac-related gastrointestinal ulcers.A disproportionality analysis was conducted utilizing the Bayesian confidence propagation neural network of information component(IC)and reporting odds ratio(ROR)methods.All statistical analyses were performed using R version 3.6.1.The findings demonstrated a significant signal for gastrointestinal ulcers associated with Tac use,with a ROR1 of 1.87(95%CI:1.68-2.08)and an IC1 of 0.89(95%CI:0.73-1.05)when compared to all other drugs.When compared specifically to cyclosporine,Tac also showed a significant signal(ROR2=1.55,95%CI:1.28-1.86;IC2=0.24,95%CI:0.04-0.44).Further analysis identified age,male gender,and European descent as risk factors for mortality outcomes in patients with Tac-associated gastrointestinal ulcers.These findings highlighted the critical need for clinicians to strengthen the monitoring and early detection of gastrointestinal ulcers in patients undergoing Tac therapy.Enhanced vigilance in this regard is essential to optimize the management and care of transplant patients.展开更多
Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementa...Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementation of these animal experiments and potentially clinical trials,it is crucial to assess the renal safety of CAR-T therapies using real-world safety evidence.Methods:Our focus was on utilizing 4 algorithms,including disproportionality analysis,based on the US Food and Drug Administration Adverse Event Reporting System database,to filter positive signals of acute and chronic renal injury associated with 6 CAR-T therapies.Further determination of causality was achieved through Mendelian randomization(MR)for drugs associated with renal injury events showing a correlation.Results:Six therapies were evaluated involving a total of 9,770 patients,with only acute kidney injury(AKI)identified as associated with idecabtagene vicleucel treatment using 4 algorithmic thresholds,including disproportionality analysis.Subsequently,MR revealed no causal relationship between the idecabtagene vicleucel target B cell maturation antigen and the risk of AKI(P=0.576),a finding validated in another independent dataset(P=0.734).Conclusion:CAR-T therapies do not directly cause renal damage and necessitate controlling adverse renal risks during or after treatment,such as cytokine release syndrome.Future research efforts should rigorously optimize these aspects to better cater to nephrologists’requirements.展开更多
文摘Tacrolimus(Tac)is a cornerstone immunosuppressant in the treatment regimens for organ transplant recipients.However,its extensive clinical use has brought attention to its associated drug safety concerns.Recent case reports highlighting Tac-induced gastrointestinal ulcers have prompted further investigation.In the present study,we analyzed Tac-associated adverse events using data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)to identify potential adverse event signals.Adverse event reports were collected up to the third quarter(Q3)of 2023,revealing 339 cases of Tac-related gastrointestinal ulcers.A disproportionality analysis was conducted utilizing the Bayesian confidence propagation neural network of information component(IC)and reporting odds ratio(ROR)methods.All statistical analyses were performed using R version 3.6.1.The findings demonstrated a significant signal for gastrointestinal ulcers associated with Tac use,with a ROR1 of 1.87(95%CI:1.68-2.08)and an IC1 of 0.89(95%CI:0.73-1.05)when compared to all other drugs.When compared specifically to cyclosporine,Tac also showed a significant signal(ROR2=1.55,95%CI:1.28-1.86;IC2=0.24,95%CI:0.04-0.44).Further analysis identified age,male gender,and European descent as risk factors for mortality outcomes in patients with Tac-associated gastrointestinal ulcers.These findings highlighted the critical need for clinicians to strengthen the monitoring and early detection of gastrointestinal ulcers in patients undergoing Tac therapy.Enhanced vigilance in this regard is essential to optimize the management and care of transplant patients.
基金supported by grants from the National Natural Science Foundation of China(82470736,22321005,824B2015,82170711,82070733)Beijing Nova Program(20220484147,20240484677)+4 种基金Beijing Natural Science Foun dation(7242144)the National Key Research and Development Program of China(2024YFC2511000)the Funda mental Research Funds for the Central Universities(Peking University Clinical Scientist Training Program)(BMU2024 PYJH021)the National High Level Hospital Clinical Research Funding(Interdisciplinary Research Project of Peking University First Hospital)(2023IR12)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046).
文摘Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementation of these animal experiments and potentially clinical trials,it is crucial to assess the renal safety of CAR-T therapies using real-world safety evidence.Methods:Our focus was on utilizing 4 algorithms,including disproportionality analysis,based on the US Food and Drug Administration Adverse Event Reporting System database,to filter positive signals of acute and chronic renal injury associated with 6 CAR-T therapies.Further determination of causality was achieved through Mendelian randomization(MR)for drugs associated with renal injury events showing a correlation.Results:Six therapies were evaluated involving a total of 9,770 patients,with only acute kidney injury(AKI)identified as associated with idecabtagene vicleucel treatment using 4 algorithmic thresholds,including disproportionality analysis.Subsequently,MR revealed no causal relationship between the idecabtagene vicleucel target B cell maturation antigen and the risk of AKI(P=0.576),a finding validated in another independent dataset(P=0.734).Conclusion:CAR-T therapies do not directly cause renal damage and necessitate controlling adverse renal risks during or after treatment,such as cytokine release syndrome.Future research efforts should rigorously optimize these aspects to better cater to nephrologists’requirements.
