Ipilimumab-associated colitis or refractory<i>Clostridium difficile</i>infection?

Gupta, Arjun; Khanna, Sahil

doi:10.1136/bcr-2015-211160

Cited by 14 publications

(18 citation statements)

References 17 publications

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“…So far, no definitive correlation between stool calprotectin levels – a marker of neutrophil‐associated inflammation – and the occurrence of diarrhea or colitis has been established . It is still unclear whether autoimmune colitis is triggered by infectious agents; there are, however, reports of an association with Salmonella or Clostridium infections . In a small cohort of 33 patients, serum interleukin‐17 levels prior to treatment correlated with the risk of severe diarrhea/colitis .…”

Section: Organ‐specific Side Effects During Immune Checkpoint Blockadementioning

confidence: 99%

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Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma

Kähler

Hassel

Heinzerling

et al. 2016

J Deutsche Derma Gesell

172

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SummaryCTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management.

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Section: Organ‐specific Side Effects During Immune Checkpoint Blockadementioning

confidence: 99%

“…Bislang ist unklar, ob die autoimmune Kolitis über infektiöse Erreger getriggert wird, es gibt aber Berichte über eine Assoziation mit einer Salmonellen-bzw. Clostridien-Infektion [ 16 ] . In einer kleinen Kohorte von 33…”

Section: Diarrhö/kolitisunclassified

Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma

Kähler

Hassel

Heinzerling

et al. 2016

J Deutsche Derma Gesell

172

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“…Of the 1892 unique studies identified using our search criteria, 61 studies fulfilled our inclusion criteria and were included in the qualitative analysis (38 full text articles, 23 in abstract form) . Results of our search strategy are depicted in Figure .…”

Section: Resultsmentioning

confidence: 99%

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

Wright

Piper

Bishu

et al. 2019

Aliment Pharmacol Ther

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Summary Background Immune checkpoint inhibitors are used in the treatment of multiple advanced stage cancers but can induce immune‐mediated colitis necessitating treatment with immunosuppressive medications. Diagnostic colonoscopy is often performed but requires bowel preparation and may delay diagnosis and treatment. Sigmoidoscopy can be performed rapidly without oral bowel preparation or sedation. Aims Characterize the colonic distribution of immune‐mediated colitis to determine the most efficient endoscopic approach. Methods A systematic review of checkpoint inhibitor‐induced colitis case reports and series was conducted in both PubMed and Embase through 3 January 2017. A single centre retrospective chart review of patients who underwent endoscopic evaluation for diarrhoea after treatment with a checkpoint inhibitor (ipilimumab, nivolumab or pembrolizumab) between 1 January 2011 and 3 January 2017 was performed. Clinical, endoscopic and histologic data were collected. Results A detailed systematic review resulted in 61 studies, in which 226 cases of colitis were diagnosed by lower endoscopy (125 colonoscopy, 101 sigmoidoscopy). Only four patients had isolated findings proximal to the left colon. In our centre, 31 patients had histologic features of checkpoint inhibitor‐induced colitis, for which 29 patients had complete data. The left colon was involved in all cases. Sigmoidoscopy would be sufficient to diagnose >98% of reported cases of checkpoint inhibitor‐mediated colitis diagnosed by lower endoscopy. Conclusions Moderate to severe checkpoint inhibitor‐induced colitis involves the left colon in the majority of cases (>98%). Sigmoidoscopy should be the initial endoscopic procedure in the evaluation of this condition.

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“…Bacteroidetes phylum war mit einer geringeren, Firmicutes mit einer erhöhten Colitis-Rate assoziiert[31,32]. Bislang ist unklar, ob die autoimmune Colitis über infektiöse Erreger getriggert wird, es gibt aber Berichte über eine Assoziation mit einer Salmonellen-beziehungsweise Clostridien-Infektion[33]. In einer ersten Studie wurden zwei therapierefraktäre Patienten mit autoimmuner Colitis mittels Transplantation von 50 g Stuhl eines gesunden Probanden behandelt[34].…”

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Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD‐1‐Antikörper beim metastasierten Melanom – ein Update

Kähler

Hassel

Heinzerling

et al. 2020

J Deutsche Derma Gesell

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EinleitungDie Immun-Checkpoint-Inhibition (ICI) hat die medikamentöse Tumortherapie in den letzten zehn Jahren revolutioniert, wobei das metastasierte Melanom bei der Entwicklung dieser Therapie die führende Indikation war [1]. Eine Vielzahl von Immun-Checkpoints sind bekannt. Zur Tumortherapie zugelassene Antikörper sind momentan verfügbar zur Blockade der Checkpoints CTLA-4 (cytotoxic T-lymphocyte antigen 4, Ipilimumab) und PD-1 (programmed cell death protein 1, Nivolumab, Pembrolizumab, Cemiplimab) beziehungsweise dessen Liganden PD-L1 (Avelumab, Atezolizumab, Durvalumab). Diese Antikörper werden bei zahlreichen Tumorentitäten eingesetzt, neben den Hauttumoren (Melanom, kutanes Plattenepithelkarzinom und Merkelzellkarzinom) gehören dazu Bronchial-, Mamma-, Nieren-, Leber-, Harnblasen-und Kopf-Hals-Tumoren. Der therapeutische Eingriff in die Regulation des Immunsystems hat aber auch Nebenwirkungen, die auf dem Wirkmechanismus beruhen. So kann es zu Entzündungen in unterschiedlichen Organen kommen, die teilweise lebensbedrohlich sein können und ein schnelles Handeln erfordern. Dieser Artikel bietet ein Update zu unserer Übersicht von 2016 [2] und soll den aktuellen Kenntnisstand zu den Nebenwirkungen und dem Management von Immun-Checkpoint-Inhibitoren zusammenfassen. Eine so intensivierte Immunantwort bringt unvermeidlich auch Nebenwirkungen mit sich. Das Wissen um dieses Nebenwirkungsspektrum ist für die Prophylaxe und das Management notwendig. Es kommt zu Nebenwirkungen wie Colitis, Dermatitis, Hypophysitis, Thyreoiditis, Hepatitis und weiteren, selteneren Autoimmunphänomenen. Die Erkennung und Therapie der genannten Autoimmunnebenwirkungen sind inzwischen gut bekannt. Insbesondere die frühe Diagnose seltener, aber mit einer höheren Letalität verbundenen neurologischen oder kardiologischen Nebenwirkungen ist häufig schwierig. Dieses Update beschreibt das aktuelle Nebenwirkungsspektrum und -Management unter Immun-Checkpoint-Inhibition sowie neue Erkenntnisse zu diesem Themenfeld. SummaryCTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforemention...

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Ipilimumab-associated colitis or refractoryClostridium difficileinfection?

Cited by 14 publications

References 17 publications

Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma

Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD‐1‐Antikörper beim metastasierten Melanom – ein Update

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