Systematic review with meta‐analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease

Piovani, Daniele; Danese, Silvio; Peyrin–Biroulet, Laurent; Nikolopoulos, Georgios K.; Bonovas, Stefanos

doi:10.1111/apt.15692

Cited by 61 publications

(51 citation statements)

References 52 publications

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“…reported the high expression of ACE2 in enterocytes and the readily infected enterocytes by 2019-nCoV [ 28 ]. However, Lines of evidence suggest the increased risk for 2019-nCoV infection of pregnant and older patients with IBD [ 29 , 30 ], pointing out the putative hazard of ACEIs or ARBs administration. In conclusion, neither ACE2 downregulation nor ACEI is the ideal treatment for COVID-19 patients with gut diseases, and combination therapy of ACEI and calcium blocker merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

ACE2 contributes to the maintenance of mouse epithelial barrier function

Liu

et al. 2020

Biochemical and Biophysical Research Communications

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Background The whole world was hit hard by the coronavirus disease-19 (COVID-19). Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. Methods: We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. Inflammatory bowel disease (IBD) mouse model was established by 4% dextran sodium sulfate. LGR5 and KI67 levels were quantitated to reflect the virtue of intestinal stem cells (ISCs). FITC-dextran 4 (FD-4) assay was used to assess intestinal barrier function. Results: Western blotting identified the expression of ACE2 in colon, which was consistent with the results of immunofluorescence and RT-PCR. Moreover, Ace2 −/− organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2 −/− organoids was markedly increased compared with ace2 +/+ organoids. Collectively, ace2 −/− mice were more susceptible than ace2 +/+ mice to IBD, including earlier bloody stool, undermined intestinal architecture and more pronounced weight loss. Conclusions: Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.

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Section: Discussionmentioning

confidence: 99%

ACE2 contributes to the maintenance of mouse epithelial barrier function

Liu

et al. 2020

Biochemical and Biophysical Research Communications

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“…Both Piovani et al (RR 2.70, 95% CI 1.56–4.66, serious infections) and Borren and Ananthakrishnan (OR 11.22; 95% CI 3.60–34.99, any infection) found that the risk of infections was substantially increased when comparing older anti-TNF users to older non-users. [ 14 , 15 ]…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events

Asscher

Vliet

Aalst

et al. 2020

Int J Colorectal Dis

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Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. Methods Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

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“…90 91 Other covid-19 risks situation comprise older patients with IBD with comorbidities as well as patients suffering from malnutrition who may be at risk for infections and severe courses of the disease, respectively. [92][93][94][95] Furthermore, dependent on the local situation, there could be an increased risk for covid-19 in the context of IBD surgery in the hospital. Finally, experimental covid-19 treatment with hydroxychloroquine or remdesivir may increase the risks for drug-drug interactions with established IBD medications ( www.…”

Section: Immunotherapy In Ibd: Potential Effects On Covid-19mentioning

confidence: 99%

COVID-19 and immunomodulation in IBD

Neurath

2020

Gut

270

310

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The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

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Systematic review with meta‐analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease

Cited by 61 publications

References 52 publications

ACE2 contributes to the maintenance of mouse epithelial barrier function

ACE2 contributes to the maintenance of mouse epithelial barrier function

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events

COVID-19 and immunomodulation in IBD

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