A Potential New Use for Tocilizumab: Refractory Checkpoint Inhibitor Hepatitis

Lyles, Laine; Farmer, Reagan; Abougergi, Marwan

doi:10.14309/crj.0000000000001162

Cited by 2 publications

(1 citation statement)

References 10 publications

(14 reference statements)

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“…Most experts recommend a liver biopsy if not already done in 2nd line nonresponders to exclude other causes of liver injury along with discussion regarding anticipated risk vs. benefit of additional immunosuppression [19,23]. Published case series demonstrate the potential utility of oral tacrolimus (1-2 mg bid with target trough of 8-10 ng/ml), intravenous tocilizumab (8 mg/kg), intravenous infliximab (5 mg/kg) and other agents in refractory patients but there is no consensus as to a preferred agent or when to start them [35][36][37]. A hospitalized patient with steroid refractory ILICI with jaundice and severe necrosis on biopsy responded to antithymocyte globulin (1.5 mg/kg) but overall risk vs. benefit should be considered [38].…”

Section: Management Of Immune-mediated Liver Injury From Checkpoint I...mentioning

confidence: 99%

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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Purpose of review The aim is to summarize the latest data on the incidence, clinical manifestations, and management of immune- mediated liver injury from checkpoint inhibitors (ILICI). Recent findings ILICI develops in 10–15% of oncology patients receiving immunotherapy with most having asymptomatic serum aminotransferase and/or alkaline phosphatase elevations. Most grade 1–2 ILICI patients improve with drug discontinuation and/or short-term oral corticosteroids. In contrast, the 2–3% with grade 3/4 hepatotoxicity frequently require oral or intravenous corticosteroids and some are hospitalized to initiate further immunosuppression with mycophenolate mofetil or azathioprine. Liver biopsy is generally reserved for patients with atypical features or those with severe hepatotoxicity who fail to respond to treatment. Up to 3% of ILICI patients with a cholestatic profile have MRI evidence of intra or extrahepatic cholangitis that responds poorly to immunosuppression. Most ILICI patients improve during follow-up and liver-related death is very uncommon (<1%). Up to 30% of rechallenged ILICI patients develop recurrent hepatotoxicity with a shorter latency. Summary ILICI is increasingly encountered by gastroenterologists evaluating oncology patients with abnormal liver biochemistries. A stepwise approach to exclude viral hepatitis, alcohol, hepatic metastases, and pancreaticobiliary disease is recommended. The majority of ILICI patients fully recover with ICI discontinuation and short-term corticosteroids or a second line immunosuppressant.

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Section: Management Of Immune-mediated Liver Injury From Checkpoint I...mentioning

confidence: 99%

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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Systematic review of immune checkpoint inhibitor-related gastrointestinal, hepatobiliary, and pancreatic adverse events

Shatila,

Zhang,

Shirwaikar Thomas

et al. 2024

J Immunother Cancer

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Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity of immunotherapy were excluded. We excluded certain article types depending on whether stronger evidence was available in the literature for a specific toxicity, for example, if prospective studies were available on a topic, retrospective studies and case reports were excluded. We extracted a final 166 articles for our review and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data reporting. Risk of bias tools were not used to evaluate the extracted studies given the narrative nature of this manuscript, but each study was critically appraised by the manuscript writer. We detail the incidence, presentation, evaluation, management, and outcomes of the various GI toxicities that may arise with ICI therapy. Specifically, we discuss the characteristics of upper GI toxicity (esophagitis and gastroenteritis), lower GI toxicity (colitis), hepatobiliary inflammation, pancreatitis, and rarer forms of GI toxicity. We hope this review serves as a useful and accessible clinical tool that helps physicians familiarize themselves with the nuances of gastrointestinal/hepatic/pancreatic ICI toxicity diagnosis and management.

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A Potential New Use for Tocilizumab: Refractory Checkpoint Inhibitor Hepatitis

Cited by 2 publications

References 10 publications

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Systematic review of immune checkpoint inhibitor-related gastrointestinal, hepatobiliary, and pancreatic adverse events

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