Background & Objectives
The ORAL Surveillance trial (NCT02092467), a postauthorization safety study of tofacitinib in patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor, found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events when patients were treated with tofacitinib vs. a tumor necrosis factor (TNF) inhibitor. To further our understanding of the VTE events identified in the trial, Charles-Schoeman et al. assessed the incidence of VTE in patients with RA over time. They also explored risk factors of VTE, including disease activity.
Methods
Patients with RA aged 50 years or older and with at least one additional cardiovascular risk factor received 5 or 10 mg of tofacitinib twice daily or a TNF inhibitor. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by six-month intervals were estimated for adjudicated VTE, deep vein thrombosis and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE.
Results
Cumulative probabilities for venous thromboembolism and pulmonary embolism were higher with 10 mg of tofacitinib twice daily, but not 5 mg of tofacitinib twice daily, compared with TNF inhibitor. Incidence rates were consistent across six-month intervals within treatments. Across treatments, risk factors for VTE included prior occurrence of VTE, body mass index greater than or equal to 35 kg/m2, older age (i.e., age 65 years or older) and a history of chronic lung disease. At the time of the event, most patients with VTE had active disease, as defined by Clinical Disease Activity Index.
Conclusions
The cumulative incidence of VTE and PE events was higher with 10 mg of tofacitinib twice daily vs. TNF inhibitor, and the results 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 when considering initiation of tofacitinib or a TNF inhibitor in patients with active RA.
For complete details, including source material, refer to the full study.
Excerpted and Adapted From
Charles-Schoeman C, Fleischmann R, Mysler E, et al. Risk of venous thromboembolism with tofacitinib versus tumor necrosis factor inhibitors in cardiovascular risk-enriched rheumatoid arthritis patients. Arthritis Rheumatol. 2024 Aug;76(8).
