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Nephrotoxicity of immune checkpoint inhibitor therapy: a pharmacovigilance study
Lorine Haeuser1,2, Maya Marchese1, Eugene B Cone1
1Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Background:
Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADRs) occur in every organ system, often due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes would be reported more frequently in association with ICIs.
Methods:
We analyzed VigiBase, the World Health Organization pharmacovigilance database, to identify renal ADRs (rADRs), such as nephritis, nephropathy and vascular disorders, reported in association with ICI therapy. We performed a disproportionality analysis to explore if rADRs were reported at a different rate with one of the ICI drugs compared with rADRs in the entire database, using an empirical Bayes estimator as a significance screen and defining the effect size with a reporting odds ratio (ROR).
Results:
We found 2341 rADR for all examined ICI drugs, with a disproportionality signal solely for nephritis [ROR = 3.67, 95% confidence interval (CI) 3.34-4.04]. Examining the different drugs separately, pembrolizumab, nivolumab and ipilimumab + nivolumab combination therapy had significantly higher reporting odds of nephritis than the other ICI drugs (ROR = 4.54, 95% CI 3.81-5.4; ROR = 3.94, 95% CI 3.40-4.56; ROR 3.59, 95% CI 2.71-4.76, respectively).
Conclusions:
Using a pharmacovigilance method, we found increased odds of nephritis when examining rADRs associated with ICI therapy. Pembrolizumab, nivolumab and a combination of ipilimumab + nivolumab showed the highest odds. Clinicians should consider these findings and be aware of the increased risk of nephritis, especially in patients treated with pembrolizumab, when administering ICI therapy.
Insights
Immune checkpoint inhibitors (ICIs) increase the risk of nephritis, a kidney inflammation. Pembrolizumab and nivolumab showed the highest odds of causing this adverse drug reaction.
Area of Science:
- Nephrology
- Oncology
- Pharmacovigilance
Background:
- Immune checkpoint inhibitor (ICI) therapy offers significant cancer treatment benefits.
- Adverse drug reactions (ADRs) from ICIs can affect any organ system, often mimicking autoimmune conditions.
- Investigating ICI-associated nephrotoxicity is crucial for patient safety.
Purpose of the Study:
- To analyze the association between ICI therapy and nephrotoxicity using a global pharmacovigilance database.
- To identify specific renal adverse drug reactions (rADRs) linked to ICI use.
- To hypothesize increased reporting of inflammatory nephrotoxic syndromes with ICIs.
Main Methods:
- Utilized VigiBase, the WHO pharmacovigilance database, for identifying renal ADRs.
- Conducted a disproportionality analysis comparing ICI drugs against the entire database for rADRs.
- Employed an empirical Bayes estimator and reporting odds ratio (ROR) for statistical significance and effect size.
Main Results:
- Identified 2341 renal ADRs across all examined ICI drugs.
- A significant disproportionality signal for nephritis was observed (ROR = 3.67).
- Pembrolizumab, nivolumab, and ipilimumab + nivolumab combination therapy showed significantly higher odds of nephritis.
Conclusions:
- Pharmacovigilance analysis revealed increased odds of nephritis associated with ICI therapy.
- Pembrolizumab and nivolumab, individually or in combination, present the highest risk for ICI-induced nephritis.
- Clinicians must remain vigilant for nephritis in patients receiving ICI therapy, particularly those on pembrolizumab.
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