Risk of Venous Thromboembolism with Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk‐enriched Rheumatoid Arthritis Patients

Objective The ORAL Surveillance trial found a dose‐dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Methods Patients with rheumatoid arthritis (RA) aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (IRs; patients with first events/100 patient‐years) by 6‐month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index (CDAI) leading up to the event was explored in patients with VTE. Results Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. IRs were consistent across 6‐month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index (BMI) ≥35 kg/m 2 , older age, and history of chronic lung disease. At the time of the event, most patients with VTE had CDAI‐defined active disease. Conclusion Incidences of VTE and PE were higher with tofacitinib (10>5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, BMI, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.