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

ABSTRACT: 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.

SUBMITTER: Wright AP

PROVIDER: S-EPMC6637018 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Wright Andrew P AP Piper Marc S MS Bishu Shrinivas S Stidham Ryan W RW

Alimentary pharmacology & therapeutics 20190429 12

<h4>Background</h4>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.<h4>Aims</h4>Characterize the colonic distribution of immune-mediated colitis to determine the mos ...[more]

PMID: 31035308

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immune-mediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis.MethodsWe evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups.ResultsOf the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti-PD-1) or of its ligand (anti-PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) therapy alone or combined with anti-PD-1/L1. Anti-CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti-CTLA-4 and anti-PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P = 0.03).ConclusionsICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear.

Project description:BackgroundAlong with the increasing use of immune checkpoint inhibitors comes a surge in immune-related toxicity. Here, we review the currently available data regarding neurological immune adverse events, and more specifically aseptic meningitis and encephalitis, and present treatment and diagnostic recommendations. Furthermore, we present five cases of immunotherapy-induced aseptic meningitis and encephalitis treated at our institution.Recent findingsNeurological immune-related adverse events, including aseptic meningitis and encephalitis, secondary to checkpoint inhibitors are a rare but complex and clinically relevant entity, comprising a wide range of diseases, most often presenting with symptoms with a wide range of differential diagnoses. Our case-series highlights the challenges of such entities and the importance of properly identifying and managing aseptic meningitis and encephalitis.SummaryCheckpoint inhibitor-induced meningoencephalitis warrants prompt investigations and treatment. Properly diagnosing aseptic meningitis, encephalitis, or mixed presentations may guide the treatment decision, as highlighted by our case-series. After rapid exclusion of alternative diagnoses, urgent corticosteroids are the therapeutic backbone but this could change in favour of highly specific cytokine-directed treatment options.Plain language summaryAseptic meningitis and encephalitis with immune checkpoint inhibitors: a single centre case-series and review of the literature Over the course of the past decade, checkpoint inhibitors have revolutionized cancer care. With their favourable toxicity profile and potential for durable and deep responses, they have become ubiquitous across the field of oncology. Furthermore, combination checkpoint inhibitors are also gaining ground, with increased efficacy and, unfortunately, immune-related toxicity. While there are guidelines based on extensive clinical experience for frequent adverse events, uncommon entities are less readily identified and treated. Neurological immune-related adverse events secondary to checkpoint inhibitors are a rare but complex entity, comprising a wide range of diseases, most often presenting with aspecific symptoms. In this paper, we discuss a single institution case-series of patients with autoimmune aseptic meningitis and encephalitis, and we perform a narrative literature review on this subject. We conclude with our treatment recommendations based on available evidence.

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

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

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