Case Series of Ventricular Tachycardia and Myocarditis From Programmed Cell-Death Protein-1 Inhibitor Treated With Infliximab

Padegimas, Allison; Agarwal, Parul; Fleitman, Jessica; Carver, Joseph R.; Rao, Sriram; Mather, Paul; Domenico, Christopher; Nazarian, Saman; Riley, Michael P.; O’Quinn, Rupal

doi:10.1016/j.jacep.2019.05.001

Cited by 8 publications

(12 citation statements)

References 3 publications

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“…Steroid use is based on its anti-inflammatory action and decreasing inflammation size. In addition to corticosteroid, immunosuppressive agents as infliximab [15, 17, 18, 31, 37, 38], intravenous immunoglobulin (IVG) [11, 13, 22, 24, 37, 38, 41], antithymocyte [35], and plasma exchange [19, 24, 33], and plasmapheresis [36, 38] are used as a secondary treatment after corticosteroid trial. [11] Also, myco-phenolate mofetil (MMF) [27, 28, 30] and tacrolimus [11, 20, 24, 41], tofacitinib [41], and abatacept [32] were used and they helped in the management and controlling the inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…The causes of death in the 14th mortality were as following myocardial infarction (MI) [4, 18, 23, 33], multiple organ failure (MOF) [18, 36], complete heart block (CHB) [19, 36], ventricular tachycardia (VT) [18, 40], congestive heart failure (CHF) [19, 30], PE/bacteremia [31], hypotension/diaphragmatic paralysis [37], and progressive lung cancer. [11] The follow-up time ranged from 3 days to 26 months.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

Sheikh

Patel

Nagpal³

et al. 2021

Preprint

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IntroductionImmune Checkpoint Inhibitors (ICI) are used as a single agent or as a combination therapies for early or late-stage malignancies. The common malignancies that ICI targets include the following: melanoma, lung cancer, renal cell carcinoma, and hematological malignancies such as Hodgkin’s lymphoma. ICI use is associated with many immune-related adverse events, and ICI-induced myocarditis is one of the rare and most severe AE with a high mortality rate. There are no consensus evidence-based treatment guideline; the expert recommendation is to use high-dose steroids. We aim in this review to assess the effectiveness of steroids in treating ICI-induced myocarditis.MethodsWe searched the following database Pubmed, Scopus, Cinhale, and Google Scholar, using the following keywords: ICI-induced myocarditis, treatment, steroid. We included articles in the English language, case reports, case series, and published in the last five years.Results352 articles were screened using PRISMA guidelines. After excluding the articles that were duplicate, irrelevant, and did not meet inclusion criteria, 35 articles with a total number of 50 patients were included. All patients treated with ICI either as a single or combination regimen. The onset of symptoms post initiation varied from one day to a year. 46 out of the 50 cases received high doses of Intravenous steroids as a loading dose followed by an oral or intravenous maintenance dose. Out of 50 patients 14 patients (28 %) died but 34 (68 %) patients survived, and 2 (4 %) patients data were not available. The mean age of the patients was 66.31 ± 14.071 (range 23-88 years), 29 were male (58%), 21 were female (42%). Most of the cases were from the USA (42%), followed by Australia (20 %), Japan (14%), Germany, France, and China (4%), Switzerland, Canada, and Spain (2%), and for (6%) cases. A total of 23 patients had cardiovascular comorbidities (46%), which were HTN (14 patients, 60.87%), hyperlipidemia (5 patients, 21.73%), and less than 1 % of patients had myocardial ischemia, congestive heart failure, atrial fibrillation, and peripheral vascular disease. While 26 patients (52%) had normal basal cardiac status.ConclusionOur results showed that high doses of steroids were effective in controlling cardiac myocyte inflammation and mortality by 28%. Race was not included in the analysis as it was not reported. More in – depth studies are needed to provide a broader representation of steroids in myocarditis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

Sheikh

Patel

Nagpal³

et al. 2021

Preprint

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“…Several case reports have described the ability of infliximab treatment to successfully ameliorate ICI-induced myocardial injury ( Supplementary Table S1 ). In some cases, infliximab treatment could eliminated arrhythmias and cardiac dysfunction ( Martinez-Calle et al, 2018 ; Padegimas et al, 2019 ). However, one retrospective study demonstrated that patients treated with infliximab were those with persistent evidence of cardiac dysfunction such as heart failure and ventricular tachycardia and that two of the four patients died from septic shock 2–3 months after the initial treatment ( Zhang et al, 2021 ).…”

Section: Clinical Evaluations Of Therapy Against Ici-induced Cardioto...mentioning

confidence: 99%

Drug therapy for myocarditis induced by immune checkpoint inhibitors

2023

Front. Pharmacol.

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Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and its ligand 1 (PD-L1), have improved the survival in multiple types of cancers; however, ICIs may cause cardiovascular toxicity. Although rare, ICI-mediated cardiotoxicity is an extremely serious complication with a relatively high mortality. In this review, we discuss the underlying mechanism and clinical manifestations of cardiovascular toxicity induced by ICIs. According to previous studies, multiple signaling pathways are involved in myocarditis induced by ICIs. Further, we summarize the clinical trials of drugs for the treatment of ICI-associated myocarditis. Although these drugs have shown the beneficial effects of alleviating cardiac function and reducing mortality rates, their efficacy is not optimal. Finally, we discuss the therapeutic potential of some novel compounds as well as the underlying mechanisms of their action.

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“…Since the New England Journal of Medicine first published the use of infliximab for fulminant myocarditis after immune checkpoint blockade in 2016, results from 18 patients using TNF-a antibodies for ICI-induced myocarditis have been reported (Tables 1 and 2) (71,(77)(78)(79)(80)(81)(82)(83)(84)(85)(86). The average age of these patients was 68 years; 9 of them were male.…”

Section: Tnf-a Antagonists For Ici-induced Myocarditismentioning

confidence: 99%

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis

Liu

Fang

et al. 2022

Front. Immunol.

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With anti-PD-1 antibodies serving as a representative drug, immune checkpoint inhibitors (ICIs) have become the main drugs used to treat many advanced malignant tumors. However, immune-related adverse events (irAEs), which might involve multiple organ disorders, should not be ignored. ICI-induced myocarditis is an uncommon but life-threatening irAE. Glucocorticoids are the first choice of treatment for patients with ICI-induced myocarditis, but high proportions of steroid-refractory and steroid-resistant cases persist. According to present guidelines, tumor necrosis factor alpha (TNF-α) inhibitors are recommended for patients who fail to respond to steroid therapy and suffer from severe cardiac toxicity, although evidence-based studies are lacking. On the other hand, TNF-α inhibitors are contraindicated in patients with moderate-to-severe heart failure. This review summarizes real-world data from TNF-α inhibitors and other biologic agents for ICI-induced myocarditis to provide more evidence of the efficacy and safety of TNF-α inhibitors and other biologic agents.

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Case Series of Ventricular Tachycardia and Myocarditis From Programmed Cell-Death Protein-1 Inhibitor Treated With Infliximab

Cited by 8 publications

References 3 publications

Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

Drug therapy for myocarditis induced by immune checkpoint inhibitors

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis

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