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

Abstract

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.

Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes

“…Together with other agents such as baricitinib, it interferes with the JAK-STAT signaling pathway to reduce immunopathological reactions by restricting growth factor receptors stimulation [ 52 ]. Baricitinib administration has been associated with an increased risk of thromboembolism when compared with placebo in safety studies for rheumatological diseases and COVID-19 [ 51 , 53 ]. Moreover, it is generally known that COVID-19 might propagate coagulopathies with a thrombotic diathesis [ 54 , 55 , 56 , 57 , 58 ].…”

Is there association of olanzapine and pulmonary embolism: A case report

“…The uncontrolled obesity and hyperlipidemia were considered relative to antipsychotic drugs which may lead to PE. 15 The obesity and hyperlipidemia progressed slowly which made the PE occurred slowly in the fifth year of antipsychotic drugs.…”

Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022

“…The reported side effects of JAK inhibitors include hypercholesterolemia and thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE) [ 75 ]. Caution is advised in patients with preexisting risk factors for thromboembolic events, such as higher age, obesity, smoking, history of DVT/PE or long periods of immobilization [ 76 ]. In several trials, the JAK inhibitors did not show an increased CVD risk compared to the placebo, cs-/bDMARDs or other JAK inhibitors [ 77 , 78 ].…”