REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCommunity Series in Immune Tolerance Dual Role: Advancements in Cancer and Autoimmune Diseases, Volume IIView all 11 articles
Safety and Effectiveness of Immune Checkpoint Inhibitors in Patients with Preexisting Autoimmune Diseases: A Systematic Review
Provisionally accepted
Yasmim Passos Dias1*
Viviane Sales Freire Silva1
Maria Fernanda de Carvalho2Rafael Herchenhorn2
Daniel Herchenhorn1*- 1D'or Institute for Research and Teaching, Rio de Janeiro, Brazil
- 2Institute of Medical Education, University Estácio de Sá, 1111, Presidente Vargas, Rio de Janeiro, Brazil, IDOMED - Instituto de Educabbo Medica, Rio de Janeiro, Brazil
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Immune checkpoint inhibitors (ICIs) are effective in cancer treatment but may trigger immune-related adverse events (irAEs), especially in patients with preexisting autoimmune diseases (ADs). This population is often excluded from trials due to higher risks of flares, higher rates of irAEs, and potential reduced ICI efficacy. This review examines the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with preexisting autoimmune diseases and explores emerging evidence on potential predictive biomarkers. Methods: We conducted a systematic review using PubMed/MEDLINE, searching for articles published from 2015 to 2024 in English. The research combined terms for autoimmune diseases, ICIs (anti-CTLA-4, anti-PD-1/PD-L1), and cancer types, emphasizing studies reporting safety or efficacy outcomes. Due to marked heterogeneity in study design and outcomes, findings were summarized qualitatively rather than quantitative meta-analysis. The protocol followed PRISMA guidelines and was registered in PROSPERO (CRD420251037257). Results: We synthesized recent evidence from 17 studies including 883 cancer patients with preexisting ADs treated with ICIs. The cohort predominantly included psoriasis (20.5%), rheumatoid arthritis (18%), and inflammatory bowel disease (17.2%) patients. Safety outcomes revealed that 53.5% experienced any-grade irAEs, including 27.5% with newly developed irAEs and 34.3% with autoimmune disease flares. Some patients experienced both irAEs and autoimmune flares concurrently, and 14.9% discontinued treatment due to toxicity (including 5 fatal cases, 0.5%). Treatment efficacy varied substantially, with overall response rates ranging from 11% to 50%, median PFS from 2.9 to 14.4 months, and median OS from 8.2 to 40.5 months. Significant heterogeneity in efficacy outcomes limited comparative analyses. Conclusions: These findings highlight that ICI therapy can be effective in selected patients with well-controlled autoimmune disease, but requires early monitoring, individualized treatment approaches, and multidisciplinary management of patients with coexisting autoimmune disorders.
Keywords: autoimmune disease, immune checkpoint inhibitors, Immune-related adverse events, CTLA-4, PD-1, Cancer
Received: 24 Sep 2025; Accepted: 30 Oct 2025.
Copyright: © 2025 Dias, Sales Freire Silva, de Carvalho, Herchenhorn and Herchenhorn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yasmim Passos Dias, ydiasmd@gmail.com
Daniel Herchenhorn, herchenhorn@hotmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.