Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase

Vallejo-Yagüe, Enriqueta; Weiler, Stefan; Micheroli, Raphael; Burden, Andrea M.

doi:10.1007/s40264-020-00958-9

Cited by 41 publications

(24 citation statements)

References 14 publications

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“…Similar elevated reporting for baricitinib was observed in Europe. These results support the current recommendations for cautious use of tofacitinib in patients with high thromboembolic risk and suggest the re-examination of the use of baricitinib 4 mg in Europe [ 101 ]. The caution dealing with baricitinib used in 4mg is supported by FDA decision to limit approval only to the 2 mg formulation and results from the resent meta-analysis, which suggest higher occurrence of thromboembolic events with a 4 mg dose of baricitinib than a 2 mg dose [ 102 ].…”

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Therasupporting

confidence: 85%

“…Their recommendations are to avoid such use in patients with a higher risk of thrombosis (older age, obesity, medical history of DVT/PE, or immobilization after surgery). The very recently published study presents data on the suspected adverse drug reactions (SADRs) resulted from the analysis of individual case safety reports (ICSRs) for tofacitinib and baricitinib retrieved from the World Health Organisation (WHO) global database: VigiBase [ 101 ]. For tofacitinib, the majority of reports came from the US (79.6%), followed by Canada (11.9%) and Europe (3.3%), while 97.2% of ICSRs for baricitinib were from Europe and none from US or Canada [ 97 ].…”

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

“…For tofacitinib, the majority of reports came from the US (79.6%), followed by Canada (11.9%) and Europe (3.3%), while 97.2% of ICSRs for baricitinib were from Europe and none from US or Canada [ 97 ]. This real-world study identified that patients with reported DVT or pulmonary thrombosis (PT) or PE generally had risk factors associated with thromboembolic events (older age, reporting of contraceptives, antidepressants, antithrombotic agents) [ 101 ]. Although those patients may have developed DVT or PT/PE independently of tofacitinib, the drug treatment might be an additive risk factor.…”

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

“…The real-life data from the US CORRONA registry published in 2019 demonstrated that the risk of VTE in patients receiving tofacitinib versus those treated by TNFi was not statistically significant, although numerically higher [ 103 ]. Thromboembolic safety of JAKi requires further ongoing real-world assessment to determine if a class- and dose-relationship exist, especially in the context of increased clinical usage of JAKi and recent FDA- and EMA-approved upadacitinib in August 2019 [ 101 ].…”

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

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Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Massalska

Maśliński

Ciechomska

2020

Cells

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The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.

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Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Therasupporting

confidence: 85%

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

See 2 more Smart Citations

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Massalska

Maśliński

Ciechomska

2020

Cells

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“…10,39 Furthermore, an increased incidence of thromboembolic events was also recently reported with higher doses of tofacitinib, another JAK-inhibitor used for RA. 62 Thrombotic events and other dose-related adverse effects coupled with the absence of a clear efficacy benefit in RA with the 4 md/day versus 2 mg/day dose were the primary reasons behind the FDAs failure to approve the manufacturer's first submission in 2017. 10,39 Baricitinib was approved 1 year later but only at the lower 2 mg/day dose.…”

mentioning

confidence: 99%

Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID‐19

et al. 2020

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A hyperinflammatory response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID‐19). Agents that inhibit components of the pro‐inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus‐associated kinase (JAK)‐inhibitor that interrupts the signaling of multiple cytokines implicated in COVID‐19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin‐converting‐enzyme‐2 upregulation. However, baricitinib’s immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients’ immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID‐19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID‐19 clinical trials.

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Atopic Eczema

Ardern‐Jones,

Flohr,

Reynolds

2024

Rook's Textbook of Dermatology

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Atopic dermatitis is a complex disorder that is highly heritable, but which is strongly influenced by the environment. This chapter reviews the current understanding and describes in detail important concepts in disease pathogenesis in children and adults. Epidemiological understanding, allergy and trigger factors are reviewed. Alongside a comprehensive description of how to optimise topical therapies, phototherapy and the use of classic systemic treatments, we review the most important inflammatory pathways and link these directly to modern therapeutic treatment advances, and the evidence for their effectiveness and safety.

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Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase

Cited by 41 publications

References 14 publications

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID‐19

Atopic Eczema

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