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Management of immune checkpoint inhibitor-related rheumatic adverse events.

ABSTRACT: Immune checkpoint inhibitors (ICIs), which target the programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4 signaling pathways, represent remarkable breakthroughs in cancer treatment and have improved survival among patients with a variety of malignancies. However, the wide use of ICIs is associated with a spectrum of immune-related adverse events (irAEs) that can affect any organ system, and may sometimes be life threatening. Rheumatic irAEs are not an infrequent type of irAE. In this systematic review, we consider the clinical characteristics of rheumatic irAEs, including patients with pre-existing rheumatic diseases, and focus on the management of rheumatic irAEs.

SUBMITTER: Zhou J

PROVIDER: S-EPMC6938753 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Management of immune checkpoint inhibitor-related rheumatic adverse events.

Zhou Jiaxin J Wang Hanping H Guo Xiaoxiao X Wang Qian Q Duan Lian L Si Xiaoyan X Zhang Li L Liu Xiaowei X Li Yue Y Zhang Wen W Zhang Li L

Thoracic cancer 20191124 1

Immune checkpoint inhibitors (ICIs), which target the programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4 signaling pathways, represent remarkable breakthroughs in cancer treatment and have improved survival among patients with a variety of malignancies. However, the wide use of ICIs is associated with a spectrum of immune-related adverse events (irAEs) that can affect any organ system, and may sometimes be life threatening. Rheumatic irAEs are not an infrequent type ...[more]

PMID: 31762209

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to "monoclonal antibody," "anti-CLTA4 antibody," and "melanoma". This was followed by a rise in interest related to "sarcoidosis," "safety," "inflammatory arthritis," and "preexisting autoimmune."ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied.MethodsWe analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany.ResultsOf the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis (n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia (n = 2) and myositis (n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40-420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p < 0.0001).ConclusionRh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).

Dataset Information

Management of immune checkpoint inhibitor-related rheumatic adverse events.

Publications

Management of immune checkpoint inhibitor-related rheumatic adverse events.

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