S879 IL12/23 Blockade for Refractory Immune-Mediated Colitis: A Case Series From Two Centers

Thomas, Anusha Shirwaikar; Lee, Seung Eun; Shatila, Malek; Faleck, David; Wang, Yinghong

doi:10.14309/01.ajg.0000860156.49316.7c

Cited by 4 publications

(6 citation statements)

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“…[45][46][47] Gut-selective anti-integrin vedolizumab is an alternative to infliximab, dosed at 300 mg IV at 0, 2 and 6 weeks. 49 Case reports have also described the clinical response to faecal microbiota transplantation, [50][51][52] tofacitinib, 53,54 and extracorporeal photophoresis. 55 These additional therapies have a basis in the scientific understanding of checkpoint inhibitor colitis: ustekinumab blocks the interleukin-12/23 receptors to enhance the activity of helper T cells 1 and 17, facilitating mucosal healing 56 ; the gut microbiome plays a role in local immunoregulation and inflammation (though mechanisms linking microbial profiles to ICI colitis remain poorly defined) 57 ; interferon-gamma pathways (inhibited by tofacitinib) are critical in antitumor immunity 58 and have been implicated in ICI colitis through a tissue-resident population of CD8+ memory T cells.…”

Section: Managementmentioning

confidence: 99%

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

Townsend,

Benque,

et al. 2024

Aliment Pharmacol Ther

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SummaryBackgroundImmune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune‐related adverse events (irAEs) which can impact multiple organ systems. Onco‐Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment‐related complications. Gastroenterologists must be prepared to identify and manage diverse immune‐mediated toxicities including enterocolitis, hepatitis, pancreatitis and other ICI‐induced toxicities.AimTo provide a narrative review of the epidemiology, diagnostic evaluation and management of checkpoint inhibitor‐induced gastrointestinal and hepatic toxicities.MethodsWe searched Cochrane and PubMed databases for articles published through August 2023.ResultsGastrointestinal and hepatic irAEs include most commonly enterocolitis and hepatitis, but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) and other rarer toxicities. Guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society for Medical Oncology, in combination with emerging cohort and clinical trial data, offer strategies for management of ICI toxicities. Evaluation of irAEs severity by formal classification and clinical stability, and a thorough workup for alternative etiologies which may clinically mimic irAEs underlie initial management. Treatments include corticosteroids, biologics and other immunosuppressive agents plus supportive care; decisions on dosing, timing and choice of steroid adjuncts and potential for subsequent checkpoint inhibitor dosing are nuanced and toxicity‐specific.ConclusionsExpanding clinical trial and cohort data have clarified the epidemiology and clinical characteristics of gastrointestinal, pancreatic and hepatic toxicities of ICIs. Guidelines, though valuable, remain based principally on retrospective cohort data. Quality prospective, controlled studies may refine algorithms for treatment and potential immunotherapy rechallenge.

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Section: Managementmentioning

confidence: 99%

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

Townsend,

Benque,

et al. 2024

Aliment Pharmacol Ther

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“…Clinical evidence for its efficacy in ICI colitis has been described in case reports of patients with refractory colitis despite infliximab and vedolizumab. 33 , 34 Recently, ustekinumab was used as a first-line biologic in a case of concurrent ICI colitis and ICI hepatitis to avoid the potential hepatotoxicity associated with infliximab, with successful resolution of both irAEs. 25 …”

Section: Enterocolitismentioning

confidence: 99%

“…500-1000 mg i.v. weekly Onset: weeks CTLA4 agonist Binds B7 ligands preventing T-cell stimulation Inconclusive Myocarditis 29 Faecal microbiota transplant Favourable microbiota profile increases Treg cells, decreases proinflammatory T effector cells Possible positive effect 32 Colitis 33 , 34 CTLA4, cytotoxic T-lymphocyte antigen-4; i.v., intravenous; ICI, immune checkpoint inhibitor; IL, interleukin; JAK, Janus kinase; STAT, signal transducer and activator of transcription; Th1, T-helper 1; Th17, T-helper 17; TNF-α, tumour necrosis factor-α; Treg, T-regulatory; TRM, tissue resident memory T cells. …”

Section: Introductionmentioning

confidence: 99%

Updates in the pathogenesis and management of immune-related enterocolitis, hepatitis and cardiovascular toxicities

McKenzie,

Sneath,

Trinh

et al. 2024

Immuno-Oncology and Technology

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“…Lastly, regarding ustekinumab, the available data is not yet firmly established, with a substantial portion still derived from case reports [68][69][70][71].…”

Section: Contemporary Management In Accordance With Established Guide...mentioning

confidence: 99%

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review

Gravina,

Pellegrino,

Esposito

et al. 2024

Cancers

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Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8+ T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.

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S879 IL12/23 Blockade for Refractory Immune-Mediated Colitis: A Case Series From Two Centers

Cited by 4 publications

References 0 publications

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

Updates in the pathogenesis and management of immune-related enterocolitis, hepatitis and cardiovascular toxicities

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review

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