Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis

Castagne, Benjamin; Viprey, Marie; Martin, Julie; Schott, Anne-Marie; Cucherat, Michel; Soubrier, Martin

doi:10.1371/journal.pone.0220178

Cited by 55 publications

(48 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, there is a theoretical risk of thrombosis with tocilizumab since it alters the lipid profile. However, metaanalysis has shown that it may have better cardiovascular safety as compared with other biological DMARDs [170].…”

Section: Antirheumatic Drugs For Preventing Thrombosismentioning

confidence: 99%

Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad

2020

View full text Add to dashboard Cite

The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow's triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs.

show abstract

Section: Antirheumatic Drugs For Preventing Thrombosismentioning

confidence: 99%

Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad

2020

View full text Add to dashboard Cite

show abstract

“…Second, evidence from observational studies using mouse models supports the role of tocilizumab in treating IS [52][53]. However, this has not been con rmed using RCTs, although RCT evidence found no increased risk of adverse cardiovascular events among RA patients treated with tocilizumab compared with those receiving other biological disease-modifying antirheumatic drugs [54][55][56].…”

Section: Discussionmentioning

confidence: 99%

IL-6R Protective Variant rs7529229 Reduces Interleukin-6 Signaling and Contributes To A Decreased Ischemic Stroke Risk

Zhang

Zhao

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Interleukin-6 (IL-6) signaling is associated with an increased risk of coronary artery disease (CAD) and ischemic stroke (IS). Growing evidence shows that the minor alleles of IL-6 receptor gene (IL-6R) variants rs2228145, rs7529229, and rs4129267 significantly increase soluble IL-6R levels and reduce CAD risk. However, the role of IL-6R variants in IS is largely unknown, prompting us to perform a comprehensive analysis. Methods In stage 1 of this study, we performed a meta-analysis of three genome-wide association study datasets from MEGASTROKE, UK Biobank, and the Million Veteran Program to evaluate the association of rs7529229 with IS. In stage 2, we conducted an expression quantitative trait loci analysis to examine the effects of rs7529229 on IL-6R expression in neuropathologically healthy individuals from the UK Brain Expression Consortium, GTEx project, and the eQTLGen Consortium. In stage 3, we used a tissue-specific gene expression analysis to evaluate differences in IL-6R expression across human tissues using gene expression data from GTEx. In stage 4, we conducted a case–control gene expression analysis to explore the differential expression of IL-6R in the whole blood of IS patients and healthy controls. Results We found that: (1) the rs7529229 minor allele significantly reduced the risk of developing IS (odds ratio=0.97, 95% confidence interval 0.95–0.99, P=2.30E-03); (2) the rs7529229 minor allele significantly reduced IL-6R expression in relevant tissues especially in blood vessels and whole blood; (3) IL-6R was mainly expressed in skeletal muscle and whole blood; and (4) IL-6R expression was significantly reduced in the whole blood of healthy controls compared with IS patients. Importantly, the biological senses in stages 1–4 were all convergent. Conclusions Taken together, our findings indicate that the rs7529229 minor allele decreases IL-6R expression in relevant tissues, diminishes IL-6 signaling, and eventually reduces the IS risk. Hence, IL-6R may be a potential therapeutic target for IS. Tocilizumab, a monoclonal antibody that blocks both membrane-bound and circulating IL-6R, might be effective in treating IS or lowering its risk of development, so warrants further testing in suitably powered randomized controlled trials.

show abstract

“…Although tocilizumab significantly increases cholesterol levels and blood pressure, a recent network meta-analysis found the cardiovascular risk with tocilizumab was comparable with other disease-modifying antirheumatic drugs. 44 Regardless, given the high mortality rate among patients with COVID-19-mediated ARDS (.50%), the potential benefits of short-term tocilizumab use seem to outweigh risks of treatment for most patients.…”

Section: Immune Modulatorsmentioning

confidence: 99%

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19)

Dixon

Tassell

Vecchiè

et al. 2020

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

show abstract

Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis

Cited by 55 publications

References 58 publications

Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad

Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad

IL-6R Protective Variant rs7529229 Reduces Interleukin-6 Signaling and Contributes To A Decreased Ischemic Stroke Risk

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19)

Contact Info

Product

Resources

About