Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular...

Area of Science:

• Rheumatology
• Cardiovascular Safety
• Pharmacovigilance

Background:

• The ORAL Surveillance trial previously indicated a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) with tofacitinib compared to tumor necrosis factor inhibitors (TNFi).
• Understanding the temporal trends and risk factors for VTE in patients with rheumatoid arthritis (RA) receiving these treatments is crucial for patient safety.

Purpose of the Study:

• To assess the incidence of VTE over time in the ORAL Surveillance trial.
• To explore risk factors associated with VTE, including disease activity, in RA patients treated with tofacitinib or TNFi.

Main Methods:

• Patients aged 50+ with RA and cardiovascular risk factors received tofacitinib (5 or 10 mg BID) or TNFi.
• Cumulative probabilities and incidence rates of VTE, deep vein thrombosis, and PE were estimated at 6-month intervals.
• Cox regression models identified risk factors, and disease activity (Clinical Disease Activity Index) was examined preceding VTE events.

Main Results:

• Higher cumulative probabilities for VTE and PE were observed with tofacitinib 10 mg BID compared to TNFi; no significant difference was seen with tofacitinib 5 mg BID.
• VTE incidence rates remained consistent across 6-month intervals for each treatment group.
• Identified VTE risk factors included prior VTE, BMI ≥ 35 kg/m², older age, and chronic lung disease history. Most VTE events occurred in patients with active RA.

Conclusions:

• Incidences of VTE and PE were elevated with tofacitinib (10 mg > 5 mg BID) versus TNFi, with consistent rates over time.
• VTE risk factors identified align with previous studies in the general RA population.
• Emphasizes the importance of assessing VTE risk factors (age, BMI, VTE history) before initiating tofacitinib or TNFi in active RA patients.