Dataset Information

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis.

ABSTRACT:

Objective

We aim to characterize the incidence and relative risk of rheumatic and systemic immune-related adverse effects (irAEs) among immune checkpoint inhibitor (ICI) therapy compared with those after placebo treatment.

Methods

Randomized clinical trial studies with placebo control with the following keywords were searched from Embase, PubMed, Cochrane databases: immune checkpoint inhibitors, neoplasms, randomized controlled trials, and adverse effects.

Results

Among the 5444 published and 316 registration records, nine placebo-controlled randomized clinical trials met our selection criteria, and included data from 5560 patients. Compared with placebo use, using ICIs increases the risk of overall-rheumatic irAEs. The incidence and relative risk of all-grade rheumatic irAEs were 18.40% [95% confidence interval (CI) 12.16-25.59%, p?n?=?11), autoimmune arthritis (n?=?8), autoimmune uveitis (n?=?3), autoimmune pericarditis, bursitis, osteochondrosis, psoriasis, polymyalgia rheumatica, systemic inflammatory response syndrome, and Sjögren syndrome (n?=?1, each).

Conclusion

ICI therapy increased the incidence and relative risk of all-grade and severe rheumatic irAEs. Arthralgia was the most commonly observed non-severe irAE, while colitis and pneumonitis were commonly observed severe irAEs. Rare rheumatic irAEs like hepatitis, hypophysitis, thyroiditis, and myositis warrant special attention.

SUBMITTER: Zhang S

PROVIDER: S-EPMC7887685 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis.

Zhang Shuo S Zhou Ziyue Z Wang Li L Li Mengtao M Zhang Fengchun F Zeng Xiaofeng X

Therapeutic advances in chronic disease 20210212

<h4>Objective</h4>We aim to characterize the incidence and relative risk of rheumatic and systemic immune-related adverse effects (irAEs) among immune checkpoint inhibitor (ICI) therapy compared with those after placebo treatment.<h4>Methods</h4>Randomized clinical trial studies with placebo control with the following keywords were searched from Embase, PubMed, Cochrane databases: immune checkpoint inhibitors, neoplasms, randomized controlled trials, and adverse effects.<h4>Results</h4>Among the ...[more]

PMID: 33633822

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Project description:Unlabelled: In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended.Implications for practiceImmune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer. Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be life-threatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.

Project description:Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

Dataset Information

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis.

Objective

Methods

Results

Conclusion

Publications

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis.

Similar Datasets

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