Risk of Venous Thromboembolism Associated With Tofacitinib and Baricitinib: A Systematic Review and Indirect Meta‐Analysis

Poderós, Teresa Giménez; Borge, Sara Gallardo; Vázquez-Ferreiro, Pedro

doi:10.1002/phar.2472

Cited by 18 publications

(10 citation statements)

References 50 publications

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“…It is also high for patients receiving estrogen therapy, major surgery, or those with movement disorders ( 97 ). An indirect meta-analysis showed that tofacitinib has better VTE safety characteristics than baricitinib ( 98 ). A clinical study showed that among patients ≥50 years of age and with ≥1 cardiovascular risk factors, patients who received tofacitinib 10 mg twice a day had a higher incidence of pulmonary embolism than patients who received TNF inhibitors ( 99 ).…”

Section: Targeted Synthesis Dmardsmentioning

confidence: 99%

Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis

Yang

Zhao

et al. 2022

Front. Cardiovasc. Med.

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which can involve multiple systems. Patients with RA may have a variety of comorbidities, including cardiovascular disease (CVD), lung cancer, lymphoma, infection, osteoporosis, fatigue, depression, colon cancer, breast cancer, prostate cancer, and Alzheimer's disease. Among these comorbidities, the incidence of CVD, lung cancer, lymphoma, infection, and osteoporosis is higher. CVD is a serious complication of RA. The risk of CVD and associated mortality rate in patients with RA is high, and the treatment rate is low. In addition to traditional risk factors, such as age, sex, blood pressure, and diabetes, RA is also associated with inflammation. Furthermore, therapeutic drugs for RA, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, have beneficial or harmful effects on cardiovascular events in patients with RA. This article discusses the effects of therapeutic drugs for RA on cardiovascular events.

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Section: Targeted Synthesis Dmardsmentioning

confidence: 99%

Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis

Yang

Zhao

et al. 2022

Front. Cardiovasc. Med.

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“…During the limited placebo-controlled periods, no dose-dependent impact on the risk of VTE events was observed in tofacitinib (5 mg vs. 10 mg twice daily), baricitinib (2 mg vs. 4 mg once daily), or upadacitinib (15 mg vs. 30 mg once daily) [ 64 , 65 ]. The meta-analyses for IMIDs (including RA) showed that VTE risk was unlikely to substantially increase in patients receiving JAK inhibitor during the limited placebo-controlled periods [ 66 – 69 ]. In a stratified and meta-regression analysis, there was no interaction by dose of JAK inhibitors, indication for treatment, or length of follow-up [ 68 ].…”

Section: Vte Events In Ra Patients Receiving Jak Inhibitorsmentioning

confidence: 99%

“…In a stratified and meta-regression analysis, there was no interaction by dose of JAK inhibitors, indication for treatment, or length of follow-up [ 68 ]. In an indirect meta-analysis, the risk of VTE events in tofacitinib-treated patients was lower than in baricitinib-treated patients (OR 0.09, 95% CI 0.02–0.51), suggesting the superior safety profile of tofacitinib to baricitinib [ 69 ]. No increased risk was found for PE during treatment with JAK inhibitors for IMIDs including RA [ 70 ].…”

Section: Vte Events In Ra Patients Receiving Jak Inhibitorsmentioning

confidence: 99%

Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review

2021

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Janus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been raised regarding the risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE). A recent post hoc safety analysis of placebo-controlled trials of JAK inhibitors in rheumatoid arthritis (RA) reported an imbalance in the incidence of VTE for a 4-mg daily dose of baricitinib versus placebo. In a recent postmarketing surveillance trial for RA, a significantly higher incidence of PE was reported in treatment with tofacitinib (10 mg twice daily) compared with tofacitinib 5 mg or tumor necrosis factor inhibitors. We also experienced a case of massive PE occurring 3 months after starting baricitinib (4 mg once daily) for multiple biologic-resistant RA. Nevertheless, the evidence to support the role of JAK inhibitors in VTE risk remains insufficient. There are a number of predisposing conditions and risk factors for VTE. In addition to the known risk factors that can provoke VTE, advanced age, obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking can also contribute to its development. Greater VTE risk is noted in patients with chronic inflammatory conditions, particularly RA patients with uncontrolled disease activity and any comorbidity. Prior to the initiation of JAK inhibitors, clinicians should consider both the number and strength of VTE risk factors for each patient. In addition, clinicians should advise patients to seek prompt medical help if they develop clinical signs and symptoms that suggest VTE/PE. Key Points• Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE), especially those with uncontrolled, high disease activity and those with comorbidities.• In addition to the well-known risk factors that provoke VTE events, advanced age and cardiovascular risk factors, such as obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking, should be considered risk factors for VTE.• Although a signal of VTE/pulmonary embolism (PE) risk with JAK inhibitors has been noted in RA patients who are already at high risk, the evidence is currently insufficient to support the increased risk of VTE during RA treatment with JAK inhibitors.• If there are no suitable alternatives, clinicians should prescribe JAK inhibitors with caution, considering both the strength of individual risk factors and the cumulative weight of all risk factors for each patient.

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“…Moreover, in patients with RA treated with upadacitinib, a significantly higher efflux of cholesterol from macrophages was observed, and this was associated with increased HDLs and reduction of CRP (105). Some real-world studies reported increased major cardiovascular events (MACE) and deep venous thrombotic (DVT) events in patients treated with tofacitinib (especially at higher dose) and baricitinib (106) whereas other studies did not support these findings (107,108). Currently, it is not possible to establish if this increased risk is related to specific direct and indirect cytokine blockade, to chemical structure and/or pharmacologic and toxicologic properties of specific JAK inhibitors, to the presence of concomitant diseases, or other factors (e.g., genetic mutations).…”

Section: Signal Transduction Pathwaysmentioning

confidence: 99%

Extra-Articular Manifestations and Comorbidities in Psoriatic Disease: A Journey Into the Immunologic Crosstalk

et al. 2021

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Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.

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Risk of Venous Thromboembolism Associated With Tofacitinib and Baricitinib: A Systematic Review and Indirect Meta‐Analysis

Cited by 18 publications

References 50 publications

Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis

Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis

Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review

Extra-Articular Manifestations and Comorbidities in Psoriatic Disease: A Journey Into the Immunologic Crosstalk

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