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Preexisting autoimmune disease is a risk factor for immune-related adverse events: a meta-analysis

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Abstract

Purpose

Patients with preexisting autoimmune disease (PAD) are often excluded from clinical trials assessing immune checkpoint inhibitors (ICIs). Therefore, the safety of ICI therapy in patients with PAD remains unclear. Herein, we evaluated the incidence of immune-related adverse events (irAEs) in patients with PAD when compared with non-PAD patients.

Methods

We searched MEDLINE/PubMed, Web of Science, and Google Scholar for eligible studies from inception to January 2021. Observational studies reporting the incidence of irAEs in patients with and without PAD were included. We then performed a meta-analysis of eligible studies using forest plots. The primary endpoint of this study was the incidence rate of irAEs between patients with and without PAD.

Results

We identified three prospective and three retrospective studies involving 206 patients with PAD and 3078 patients without PAD. In the meta-analysis, 128 patients with PAD (62.1%) experienced irAEs, which occurred in 51.9% of non-PAD patients, resulting in an odds ratio (OR) of 2.14 (95% confidence interval [CI] 1.58–2.89). In the subgroup analysis, the incidence of irAEs was significantly higher in patients with PAD (OR = 2.19, 95% CI [1.55–3.08]). Furthermore, no significant heterogeneity or publication bias was detected, indicating that our meta-analysis could be generalized to clinical settings.

Conclusion

This meta-analysis demonstrated that PAD was a risk factor for irAE incidence. These results suggest that monitoring the occurrence of irAEs in patients with PAD is required to manage irAEs appropriately.

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Data availability

The dataset used for this study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan

    Atsushi Yamaguchi, Yoshitaka Saito, Keisuke Okamoto, Yoh Takekuma & Mitsuru Sugawara

  2. Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Atsushi Yamaguchi, Katsuya Narumi, Ayako Furugen & Masaki Kobayashi

  3. Laboratory of Pharmacokinetics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Mitsuru Sugawara

  4. Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Masaki Kobayashi

Authors
  1. Atsushi Yamaguchi
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  2. Yoshitaka Saito
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  4. Katsuya Narumi
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  5. Ayako Furugen
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  7. Mitsuru Sugawara
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  8. Masaki Kobayashi
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Contributions

AY, YS, and MK designed the study. AY and MK conducted the study and analyzed the data. AY, YS, MK, KO, KN, AF, YT, and MS contributed to the writing of the manuscript. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Masaki Kobayashi.

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Conflicts of interest

The authors declare no competing interests.

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Appendix: search strategy

Appendix: search strategy

We searched the related records in three databases (MEDLINE/PubMed, Web of Science, and Google Scholar), with no language restriction, from database inception to January 31, 2021. In the MEDLINE/PubMed database, we used PubMed Advanced Search Builder with the following terms: “neoplasm” AND “immune checkpoint inhibitors” AND “autoimmune disease” in all fields. In the Web of Science database, we selected all databases and conducted a basic search with the following terms: “neoplasm” AND “immune checkpoint inhibitors” AND “autoimmune disease” in the topic field. In Google Scholar, we searched articles using the advanced search feature and with the following terms: “neoplasm” AND “immune checkpoint inhibitors” AND “autoimmune disease,” with all of the words appearing anywhere in the article. Default values were chosen for all other settings.

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Yamaguchi, A., Saito, Y., Okamoto, K. et al. Preexisting autoimmune disease is a risk factor for immune-related adverse events: a meta-analysis. Support Care Cancer 29, 7747–7753 (2021). https://doi.org/10.1007/s00520-021-06359-7

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  • DOI: https://doi.org/10.1007/s00520-021-06359-7

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