Nephrotoxicity of immune checkpoint inhibitor therapy: a pharmacovigilance study
| Autor: | Lorine Haeuser, Eugene B. Cone, Joachim Noldus, Quoc-Dien Trinh, George Bayliss, Maya Marchese, Kerry L. Kilbridge |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Combination therapy 030232 urology & nephrology Ipilimumab Pembrolizumab Nephropathy Pharmacovigilance 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Internal medicine medicine Humans Immune Checkpoint Inhibitors Transplantation Nephritis business.industry Bayes Theorem Syndrome Odds ratio medicine.disease Nivolumab Nephrology 030220 oncology & carcinogenesis business medicine.drug |
| Zdroj: | Nephrology Dialysis Transplantation. 37:1310-1316 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfab187 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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