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. 2024 May;80(5):677-684.
doi: 10.1007/s00228-024-03647-z. Epub 2024 Feb 19.

Immune-related serious adverse events with immune checkpoint inhibitors: Systematic review and network meta-analysis

Clara Oliveira  1   2 , Beatrice Mainoli  1   2   3 , Gonçalo S Duarte  1   2   4 , Tiago Machado  1   2 , Rita G Tinoco  1   2   5 , Miguel Esperança-Martins  2   6 , Joaquim J Ferreira  1   2   7 , João Costa  8   9   10
Affiliations

Immune-related serious adverse events with immune checkpoint inhibitors: Systematic review and network meta-analysis

Clara Oliveira et al. Eur J Clin Pharmacol. 2024 May.

Erratum in

Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs.

Methods: We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA).

Results: We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients).

Conclusion: Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.

Keywords: Cancer; Clinical trials; Immune check-point inhibitors; Network meta-analysis; Safety; Systematic review.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Network meta-analysis of overall immune-related serious adverse events. A Network plot showing comparisons in overall immune-related serious adverse events between nodes (gray circles), each representing an intervention. The size of each node is proportional to the total number of participants assigned to the intervention. The width of each connecting line is proportional to the number of studies performing head-to-head comparisons between the two nodes. B League table showing the comparative safety profile of each intervention in terms of this outcome. Values in each cell refer to odds ratios and corresponding 95% credible intervals. The interventions are ordered alphabetically. Significant results are in bold. C Estimated absolute event rates for each intervention, expressed as rate per 10,000 patients, with corresponding 95% confidence intervals and SUCRA, expressed as a percentage, with higher values indicating a higher certainty that an intervention is superior in terms of the risk of this outcome. D Lollipop plot expressing 1-SUCRA values, where greater values indicate a greater likelihood of overall immune-related serious adverse events
Fig. 2
Fig. 2
Spider plots. Spider plots of each single ICI in relation to the treatment rank (1-SUCRA) of each immune-related serious adverse event. Greater values indicate a greater likelihood of immune-related serious adverse events
See this image and copyright information in PMC

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