Full Text:   <1636>

Summary:  <1311>

CLC number: 

On-line Access: 2021-02-07

Received: 2020-08-07

Revision Accepted: 2020-11-08

Crosschecked: 0000-00-00

Cited: 0

Clicked: 2581

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xia-hong Lin

https://orcid.org/0000-0002-5515-730X

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.2 P.156-164

http://doi.org/10.1631/jzus.B2000449


Gastrointestinal toxicities associated with immune checkpoint inhibitors: a disproportionality analysis leveraging VigiBase, the WHO Adverse Drug Reaction Database


Author(s):  Sifu HUANG, Xuefeng BAI, Taiyong FANG, Yanta GUO, Kainan ZHENG, Xiahong LIN

Affiliation(s):  Department of Gastroenterology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China; more

Corresponding email(s):   linxiahongdr@fjmu.edu.cn

Key Words: 


Sifu HUANG, Xuefeng BAI, Taiyong FANG, Yanta GUO, Kainan ZHENG, Xiahong LIN. Gastrointestinal toxicities associated with immune checkpoint inhibitors: a disproportionality analysis leveraging VigiBase, the WHO Adverse Drug Reaction Database[J]. Journal of Zhejiang University Science B, 2021, 22(2): 156-164.

@article{title="Gastrointestinal toxicities associated with immune checkpoint inhibitors: a disproportionality analysis leveraging VigiBase, the WHO Adverse Drug Reaction Database",
author="Sifu HUANG, Xuefeng BAI, Taiyong FANG, Yanta GUO, Kainan ZHENG, Xiahong LIN",
journal="Journal of Zhejiang University Science B",
volume="22",
number="2",
pages="156-164",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000449"
}

%0 Journal Article
%T Gastrointestinal toxicities associated with immune checkpoint inhibitors: a disproportionality analysis leveraging VigiBase, the WHO Adverse Drug Reaction Database
%A Sifu HUANG
%A Xuefeng BAI
%A Taiyong FANG
%A Yanta GUO
%A Kainan ZHENG
%A Xiahong LIN
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 2
%P 156-164
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000449

TY - JOUR
T1 - Gastrointestinal toxicities associated with immune checkpoint inhibitors: a disproportionality analysis leveraging VigiBase, the WHO Adverse Drug Reaction Database
A1 - Sifu HUANG
A1 - Xuefeng BAI
A1 - Taiyong FANG
A1 - Yanta GUO
A1 - Kainan ZHENG
A1 - Xiahong LIN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 2
SP - 156
EP - 164
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000449


Abstract: 
With the improvement of people's living standards, gastrointestinal adverse reactions caused by various adverse factors have attracted more and more people's attention. A recent study has indicated that coronavirus disease 2019 (COVID-19) could also invade the gastrointestinal tract, leading to gastrointestinal adverse reactions (Song et al., 2020). In recent years, immunotherapy has provided certain effects for some patients with advanced malignant tumors. A microencapsulation of immunoglobulin Y (IgY) was reported to provide an effective way to preserve IgY and improve its performance in the gastrointestinal tract (Zhang J et al., 2020). Immune checkpoint inhibitors (ICIs) can significantly improve the survival of some advanced malignant tumors, especially metastatic malignant melanoma and lung cancer (Afzal et al., 2018; Madden and Kasler, 2019). They include anti-cytotoxic T lymphocyte-associated antigen-4 (anti-CTLA-4) antibodies (ipilimumab and tremelimumab), anti-programmed cell death protein 1 (anti-PD-1) antibodies (nivolumab and pembrolizumab), and anti-programmed death-ligand 1 (anti-PD-L1) antibodies (atezolizumab, avelumab, and durvalumab) (Baxi et al., 2018). Previous studies have shown that ICI combination therapy, such as nivolumab plus ipilimumab, has particular efficacy in lung cancer, renal cell carcinoma, and malignant melanoma (Wolchok et al., 2017; Derosa et al., 2018; Doroshow et al., 2019). However, ICIs may also lead to many immune-related adverse events (irAEs), even causing severe complications in certain cases. The most well-established toxicities from ICI therapy are gastrointestinal irAEs, including enteritis, enterocolitis, microscopic colitis, and gastritis, which have attracted public attention in recent years; reports of such events associated with ICI therapy also have increased (Tandon et al., 2018; de Malet et al., 2019). These gastrointestinal irAEs may generally respond well to corticosteroids and infliximab (Haanen et al., 2017). Although most of these irAEs are low-grade, a lack of detection and timely treatment may incur severe or fatal complications.

与免疫检查点抑制剂相关的胃肠道毒性:利用WHO药物不良反应数据库VigiBase进行的不成比例分析.

目的:免疫检查点抑制剂(ICIs)可以显著提高某些晚期恶性肿瘤的生存率,但是,ICIs治疗也可能导致许多免疫相关的不良反应事件。我们的研究旨在鉴定和表征与ICIs相关的胃肠道不良反应事件。
创新点:鉴定和表征与ICIs相关的胃肠道不良反应事件,提高对ICIs所致胃肠道不良事件的认识。
方法:从世界卫生组织(WHO)药物不良反应数据库VigiBase获得2011年1月1日至2019年3月6日的药物不良反应数据,将接受ICIs治疗报告的胃肠道不良反应事件与整个数据库报告进行比较。通过计算信息成分(IC)和报告优势比(ROR)评估ICIs与胃肠道不良反应事件之间的关联。
结论:ICIs治疗可导致多种胃肠道不良反应事件,甚至可发生严重巨结肠。对于晚期恶性肿瘤患者进行ICIs临床诊疗时,需要考虑ICIs相关胃肠道不良反应事件。

关键词:免疫检查点抑制剂;胃肠道毒性;VigiBase;信息成分;报告优势比

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Abu-Sbeih H, Wang YH, 2020. Gastrointestinal tract adverse events. In: Naing A, Hajjar J (Eds.), Immunotherapy. Springer, Cham, p.247-253.

[2]Afzal MZ, Mercado RR, Shirai K, 2018. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma. J Immunother Cancer, 6:64.

[3]Baxi S, Yang A, Gennarelli RL, et al., 2018. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ, 360:k793.

[4]Cho JH, Choi JH, 2020. Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: a case report. World J Clin Cases, 8(3):552-559.

[5]de Malet A, Antoni G, Collins M, et al., 2019. Evolution and recurrence of gastrointestinal immune-related adverse events induced by immune checkpoint inhibitors. Eur J Cancer, 106:106-114.

[6]Derosa L, Hellmann MD, Spaziano M, et al., 2018. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol, 29(6):1437-1444.

[7]Doroshow DB, Sanmamed MF, Hastings K, et al., 2019. Immunotherapy in non-small cell lung cancer: facts and hopes. Clin Cancer Res, 25(15):4592-4602.

[8]Gu LH, Khadaroo PA, Su H, et al., 2019. The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis. BMC Cancer, 19:559.

[9]JBAG Haanen, Carbonnel F, Robert C, et al., 2017. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 28(Suppl_4):iv119-iv 142.

[10]Leppkes M, Ganslmayer M, Strauß R, et al., 2015. Das toxic megacolon. Med Klin Intensivmed Notfmed, 110(7):500-505.

[11]Madden K, Kasler MK, 2019. Immune checkpoint inhibitors in lung cancer and melanoma. Semin Oncol Nurs, 35(5):150932.

[12]Rodriguez-Vida A, Perez-Gracia JL, Bellmunt J, 2018. Immunotherapy combinations and sequences in urothelial cancer: facts and hopes. Clin Cancer Res, 24(24):6115-6124.

[13]Sangro B, Chan SL, Meyer T, et al., 2020. Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol, 72(2):320-341.

[14]Song M, Li ZL, Zhou YJ, et al., 2020. Gastrointestinal involvement of COVID-19 and potential faecal transmission of SARS-CoV-2. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(9):749-751.

[15]Tandon P, Bourassa-Blanchette S, Bishay K, et al., 2018. The risk of diarrhea and colitis in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis. J Immunother, 41(3):101-108.

[16]Wang DY, Ye F, Zhao SL, et al., 2017. Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: a systematic review and meta-analysis. Oncoimmunology, 6(10):e1344805.

[17]Wang DY, Salem JE, Cohen JV, et al., 2018. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol, 4(12):1721-1728.

[18]Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al., 2017. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med, 377(14):1345-1356.

[19]Xu C, Chen YP, Du XJ, et al., 2018. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ, 363:k4226.

[20]Yuan ZH, Yang HK, Wei YM, 2019. Combined induction with anti-PD-1 and anti-CTLA-4 antibodies provides synergistic antitumor effects in DC-CIK cells in renal carcinoma cell lines. Int J Clin Exp Pathol, 12(1):123-132.

[21]Zhang J, Li HH, Chen YF, et al., 2020. Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(8):611-627.

[22]Zhang ML, Neyaz A, Patil D, et al., 2020. Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies. Histopathology, 76(2):233-243.

[23]Zhao SZ, Reynolds MW, Lefkowith J, et al., 2001. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin Ther, 23(9):1478-1491.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE