What is the relative risk of venous thromboembolism (VTE) with Tofacitinib (generic name: Tofacitinib) in patients with inflammatory bowel disease (IBD)?

From the Guidelines

Tofacitinib carries an increased relative risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD), particularly at higher doses (10mg twice daily) and in those with additional risk factors, as noted in a 2021 study 1. The risk of VTE with tofacitinib is estimated to be approximately 1.5 to 3 times higher compared to patients not taking JAK inhibitors, though absolute risk remains relatively low. This risk appears dose-dependent, with higher doses carrying greater risk than lower maintenance doses (5mg twice daily). Some key points to consider when evaluating the risk of VTE in patients with IBD taking tofacitinib include:

• Disease activity: Active disease is associated with a higher risk of VTE, as noted in a 2016 study 1.
• Hospitalization: Hospitalized patients are at increased risk of VTE, with a 6-fold higher risk compared to non-hospitalized patients, as reported in a 2016 study 1.
• Colonic disease: Patients with colonic disease are at higher risk of VTE, as noted in a 2016 study 1.
• Recent surgery: Recent surgery is a risk factor for VTE, with a prevalence of 2.3% after surgery, as reported in a 2016 study 1.
• Other risk factors: Other risk factors for VTE include prolonged immobilization, central venous catheters, corticosteroids, oral contraceptives, and cigarette smoking, as noted in a 2016 study 1. Before initiating tofacitinib, clinicians should perform a thorough VTE risk assessment and consider alternative therapies in high-risk patients. During treatment, patients should be educated about warning signs of VTE (leg swelling, pain, warmth, redness, or sudden shortness of breath) and instructed to seek immediate medical attention if these occur. The increased VTE risk is thought to be related to tofacitinib's mechanism of action, as JAK inhibition affects platelet function and coagulation pathways, as noted in a 2021 study 1. Despite this risk, tofacitinib remains an important treatment option for IBD patients who have failed conventional therapies, provided appropriate risk stratification and monitoring are implemented, as noted in a 2021 study 1.

From the Research

Relative Risk of Venous Thromboembolism with Tofacitinib in IBD Patients

• The relative risk of venous thromboembolism (VTE) with Tofacitinib in patients with inflammatory bowel disease (IBD) is a significant concern, with studies suggesting an increased risk of VTE in IBD patients, particularly those with a history of VTE 2, 3.
• A retrospective cohort study found that tofacitinib did not confer a significantly elevated VTE risk compared with anti-TNF therapy (HR: 1.72,95% CI: 0.74-3.01) 4.
• However, another study suggested that patients with a prior VTE history are at high risk for recurrent VTE while receiving JAK inhibitors, and concurrent use of anticoagulation (AC) with JAK inhibitors appears to be protective against recurrent VTEs in this population 5.
• Clinical factors that increase the likelihood of a VTE event among IBD patients include older age, pregnancy, active disease, more extensive disease, hospitalization, the use of certain medications such as corticosteroids or tofacitinib, and IBD-related surgeries 2, 3.
• The use of medications such as tofacitinib may increase the likelihood of VTE in IBD patients, and outpatient prophylaxis in high-risk patients is recommended 3.
• Underutilization of anticoagulant thromboprophylaxis in hospitalized IBD patients is a concern, and prescription of thromboprophylaxis for all hospitalized IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD 6.

Key Findings

• Tofacitinib may not significantly increase the risk of VTE compared to anti-TNF therapy in IBD patients 4.
• Concurrent use of anticoagulation with JAK inhibitors may reduce the risk of recurrent VTE in patients with a prior VTE history 5.
• Clinical factors, including medication use, increase the likelihood of VTE in IBD patients 2, 3.
• Underutilization of anticoagulant thromboprophylaxis is a concern in hospitalized IBD patients 6.

Study Limitations

• The studies had varying sample sizes and populations, which may affect the generalizability of the findings 4, 5, 2, 3, 6.
• The studies used different methodologies, including retrospective cohort studies and reviews, which may introduce bias and affect the validity of the findings 4, 5, 2, 3, 6.