Reader Comment Regarding "Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management".
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ABSTRACT:
SUBMITTER: Sauder M
PROVIDER: S-EPMC8750150 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.
| S-EPMC5296331 | biostudies-literature
Project description:IntroductionCurrent epidemiologic literature of rheumatologic immune-related adverse events (rh-irAEs) consists of clinical trials, case reports, or smaller, single-center series. We evaluate the occurrence of rh-irAEs during immune checkpoint inhibitor (ICI) therapy from US commercial claims data.MethodsPatients newly initiating ICI therapy in commercial claims data were eligible for inclusion. Rh-irAEs were defined using ≥ 1 International Classification of Diseases (ICD)-9 or ICD-10-Clinical Modification (CM) claims for selected events, ranging from joint pain and myalgia to ankylosing spondylitis and psoriasis. The percentage of patients experiencing rh-irAEs after ICI initiation was determined.ResultsA total of 5722 patients initiating an ICI between January 1, 2012, and June 30, 2018, were included; 201 patients (3.5%) had a history of rheumatic disease. Among the 5521 patients without a history of rheumatic disease, 29.6% experienced ≥ 1 rh-irAE in follow-up, decreasing to 22.6% when assessing events for which there was no diagnostic history. Limiting to claims for rh-irAE with a rheumatologist provider, the proportion of patients experiencing an event decreased to 0.9%. Among patients with a history of rheumatic disease, 71.6% experienced ≥ 1 rh-irAE. Limiting to events for which the patient did not have a history during baseline, 35.3% experienced an event.ConclusionsOccurrence of rh-irAEs during ICI use is higher in patients with pre-existing rheumatic disease compared to those with no pre-existing rheumatic disease. However, the most common events were not definitive rheumatic diseases but rather symptoms, such as pain in joints. Occurrence of events associated with a rheumatologist provider was substantially lower, suggesting that either patients are not referred to a rheumatologist or referral does not result in confirmation of the diagnosis by the rheumatologist.
| S-EPMC8572292 | biostudies-literature
Project description:Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96-2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02-2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.
| S-EPMC8657283 | biostudies-literature
Project description:The development of immune checkpoint inhibitors (ICIs) has dramatically altered the landscape of therapy for multiple malignancies, including urothelial carcinoma, non-small cell lung cancer, melanoma and gastric cancer. As part of their anti-tumor properties, ICIs can enhance susceptibility to inflammatory side effects known as immune-related adverse events (irAEs), in which the skin is one of the most commonly and rapidly affected organs. Although numerous questions still remain unanswered, multi-omics technologies have shed light into immunological mechanisms, as well as the correlation between ICI-induced activation of immune systems and the incidence of cirAE (cutaneous irAEs). Therefore, we reviewed integrated biological layers of omics studies combined with clinical data for the prediction biomarkers of cirAEs based on skin pathogenesis. Here, we provide an overview of a spectrum of dermatological irAEs, discuss the pathogenesis of this "off-tumor toxicity" during ICI treatment, and summarize recently investigated biomarkers that may have predictive value for cirAEs via multi-omics approach. Finally, we demonstrate the prognostic significance of cirAEs for immune checkpoint blockades.
| S-EPMC10368482 | biostudies-literature
Project description:Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P < .0001). Concurrent usage of molecular-targeted therapy with immunotherapy was associated with a higher incidence (57.8%, P < .0001). The Kaplan-Meier plot and log-rank test showed that patients with any type of immune-related cutaneous adverse events had longer survival time than those without (P < .0001). In conclusion, having either type of cutaneous immune-related adverse event in cancer patients receiving immunotherapies was correlated with a longer overall survival. Prompt diagnosis and suitable treatment are important.
| S-EPMC9055047 | biostudies-literature
Project description:Immune checkpoint inhibition (ICI) improves outcomes in melanoma patients, but associated T-cell activation frequently leads to immune-related cutaneous adverse events (cutAEs). To dynamically identify T-cell subtypes and immune signatures associated with cutAEs, a pilot study was performed in stage III-IV melanoma patients using blood samples for flow cytometry and cytokine analysis. Blood samples were taken from patients before initiation of ICI (naive), at the onset of a cutAE, and after 6 months of ICI treatment. Overall, 30 patients were treated either with anti-PD1 monotherapy or with anti-PD-1/anti-CTLA-4 combination therapy. Flow cytometry analysis of PBMCs showed that ICI induced an overall shift from a Th2 towards a Th1 profile. Twelve patients (40%) developed cutAEs, which were associated with increased Th22 cells and Th17 cells, supported by a tendency to have elevated Th17/Th22-associated cytokines such as IL-17A, IL-22 and IL-23 levels in the plasma. Cytokine signatures specific for urticaria and T-cell-mediated cutAEs were identified in the plasma of patients by a bead-based assay. IL-10 was elevated in non-responders and, interestingly, during cutAEs. In conclusion, we identified distinct immune signatures based on the Th17/Th22 pathway in cutAEs, both in PBMCs and plasma. In addition, our finding of upregulated IL-10 during cutAEs supports the notion of treating these patients early and adequately to avoid implications for the overall outcome.
| S-EPMC10969757 | biostudies-literature
Project description: Not available
| S-EPMC10796160 | biostudies-literature
Project description:As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.
| S-EPMC7572574 | biostudies-literature
Project description:BackgroundNonphysicians are expanding practice into specialty medicine. There are limited studies on patient and physician perspectives as well as safety outcomes regarding the nonphysician practice of cosmetic procedures.ObjectiveTo identify the patient (consumer) and physician perspective on preferences, adverse events, and outcomes following cosmetic dermatology procedures performed by physicians and nonphysicians.Materials and methodsInternet-based surveys were administered to consumers of cosmetic procedures and physician members of the American Society for Dermatologic Surgery. Descriptive statistics and graphical methods were used to assess responses. Comparisons between groups were based on contingency chi-square analyses and Fisher exact tests.ResultsTwo thousand one hundred sixteen commenced the patient survey with 401 having had a cosmetic procedure performed. Fifty adverse events were reported. A higher number of burns and discoloration occurred in the nonphysician-treated group and took place more often in a spa setting. Individuals seeing nonphysicians cited motivating factors such as level of licensure (type) of nonphysician, a referral from a friend, price, and the location of the practitioner. Improper technique by the nonphysician was cited most as a reason for the adverse event. Both groups agree that more regulation should be placed on who can perform cosmetic procedures. Recall bias associated with survey data.ConclusionPatients treated by nonphysicians experienced more burns and discoloration compared with physicians, and they are encountering these nonphysicians outside a traditional medical office, which are important from a patient safety and regulatory standpoint. Motivating factors for patients seeking cosmetic procedures may also factor into the choice of provider.Key pointsBoth patients and physicians think more regulation should be in place on who can perform cosmetic procedures. More adverse events such as burns and discolorations occurred with patients seeing nonphysicians compared with those seeing physicians. In addition, for those seeing nonphysicians, a majority of these encounters took place in spa settings. Patient safety is of utmost concern when it comes to elective cosmetic medical procedures. More adverse events and encounters occurring outside traditional medical settings when nonphysicians performed these procedures call into question the required training and oversight needed for such procedures.
| S-EPMC6450566 | biostudies-literature
Project description: Not available
| S-EPMC10796159 | biostudies-literature