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      Pneumatosis intestinalis post steroid use in a patient with immune-related adverse events: Case report, literature review and FAERS analysis

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          Abstract

          Introduction: The accurate diagnosis of pneumatosis intestinalis (PI) is increasing despite patients’ limited identification of etiologic factors. Recently a patient with lung squamous carcinoma who developed pneumatosis intestinalis following methylprednisolone administration for immune-related adverse events was treated at our hospital. Subsequent a literature review and an analysis of the FDA Adverse Event Reporting System (FAERS) database enabled the identification of additional cases of pneumatosis intestinalis.

          Methods: A literature review of the MEDLINE/PubMed and Web of Science Core Collection databases using standard pneumatosis intestinalis search terms to identify published cases of immune checkpoint inhibitors (ICIs) or steroids causing pneumatosis intestinalis were performed. A separate retrospective pharmacovigilance study of FAERS enabled the extraction of unpublished cases of pneumatosis intestinalis between the first quarter of 2005 and the third quarter of 2022. Disproportionality and Bayesian analyses were performed to identify signal detection in reported odds ratios, proportional reporting ratios, information components, and empirical Bayesian geometric means.

          Results: Ten case reports of steroid-related pneumatosis intestinalis were retrieved from six published studies. The implicated drug therapies included pre-treatment with steroids before chemotherapy, combination therapy with cytotoxic agents and steroids, and monotherapy with steroids. In the FAERS pharmacovigilance study, 1,272 cases of immune checkpoint inhibitors or steroid-related pneumatosis intestinalis were incidentally reported. The signal detected in five kinds of immune checkpoint inhibitors and six kinds of steroids implied a positive correlation between the drugs and adverse events.

          Conclusion: Steroids might be the etiologic factors in the current case of pneumatosis intestinalis. Reports supporting the role of steroids in suspected cases of pneumatosis intestinalis can be found in literature databases and the FAERS database. Even so, as documented in FAERS, immune checkpoint inhibitors-induced pneumatosis intestinalis should not be excluded.

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          Most cited references32

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          Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs

          Key Points Question What is the estimated percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor drugs approved for oncology indications by the US Food and Drug Administration? Findings This cross-sectional study found that the estimated percentage of US patients with cancer who are eligible for checkpoint inhibitor drugs increased from 1.54% in 2011 to 43.63% in 2018. The percentage of patients estimated to respond to checkpoint inhibitor drugs was 0.14% in 2011 and increased to 12.46% in 2018. Meaning The estimated percentages of patients who are eligible for and who respond to checkpoint inhibitor drugs are higher than reported estimates for drugs approved for genome-driven oncology but remain modest.
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            A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions.

            A continuous systematic review of all combinations of drugs and suspected adverse reactions (ADRs) reported to a spontaneous reporting system, is necessary to optimize signal detection. To focus attention of human reviewers, quantitative procedures can be used to sift data in different ways. In various centres, different measures are used to quantify the extent to which an ADR is reported disproportionally to a certain drug compared to the generality of the database. The objective of this study is to examine the level of concordance of the various estimates to the measure used by the WHO Collaborating Centre for International ADR monitoring, the information component (IC), when applied to the dataset of the Netherlands Pharmacovigilance Foundation Lareb. The Reporting Odds Ratio--1.96 standard errors (SE), proportional reporting ratio--1.96 SE, Yule's Q--1.96 SE, the Poisson probability and Chi-square test of all 17,330 combinations were compared with the IC minus 2 standard deviations. Additionally, the concordance of the various tests, in respect to the number of reports per combination, was examined. In general, sensitivity was high in respect to the reference measure when a combination of point- and precision estimate was used. The concordance increased dramatically when the number of reports per combination increased. This study shows that the different measures used are broadly comparable when four or more cases per combination have been collected.
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              Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                14 March 2023
                2023
                : 14
                : 1133551
                Affiliations
                [1] 1 Department of Clinical Oncology , Peking University International Hospital , Beijing, China
                [2] 2 Department of Pharmacy , Beijing Tiantan Hospital , Capital Medical University , Beijing, China
                [3] 3 Department of Pharmacy , Peking Union Medical College Hospital , Peking Union Medical College , Chinese Academy of Medical Sciences , Beijing, China
                [4] 4 Department of Pharmacy , Beijing Friendship Hospital , Capital Medical University , Beijing, China
                [5] 5 Department of Pharmacy , Peking University International Hospital , Beijing, China
                [6] 6 Clinical Trial Center , Peking University International Hospital , Beijing, China
                Author notes

                Edited by: Zhi-Chun Gu, Shanghai Jiao Tong University, China

                Reviewed by: Xu Jia, Chengdu Medical College, China

                Xiaoming Hu, Fudan University, China

                *Correspondence: Li Wang, wangli@ 123456pkuih.edu.cn ; Jun Liang, liangjun_pkuih@ 123456sina.com
                [ † ]

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology

                Article
                1133551
                10.3389/fphar.2023.1133551
                10043198
                09d7d9c1-e1cc-441e-8bc8-5b4e4bab096e
                Copyright © 2023 Zhang, Cao, Zhao, Pan, Lin, Tang, Zhao, Duan, Wang and Liang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 December 2022
                : 01 March 2023
                Funding
                This work was supported by the Project of the Beijing Pharmaceutical Association (No: LCYX-2022-09) and Beijing Xisike Clinical Oncology Research Foundation (No: Y-HR2018-321).
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                pneumatosis intestinalis,steroid,lung carcinoma,immune-related adverse events,faers,immune checkpoint inhibitor

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