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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 76; no. 8; pp. 1218 - 1229
• Main Authors: Charles‐Schoeman, Christina, Fleischmann, Roy, Mysler, Eduardo, Greenwald, Maria, Ytterberg, Steven R., Koch, Gary G., Bhatt, Deepak L., Wang, Cunshan, Mikuls, Ted R., Chen, All‐shine, Connell, Carol A., Woolcott, John C., Menon, Sujatha, Chen, Yan, Lee, Kristen, Szekanecz, Zoltán
• Format: Journal Article
• Language: English
• Published: Boston, USA Wiley Periodicals, Inc 01.08.2024; Wiley Subscription Services, Inc
• Subjects: Aged; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Body mass index; Body size; Cardiovascular diseases; Embolism; Female; Health risks; Humans; Incidence; Inhibitors; Intervals; Lung diseases; Male; Middle Aged; Piperidines - adverse effects; Piperidines - therapeutic use; Population studies; Proportional Hazards Models; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pulmonary Embolism - epidemiology; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Pyrroles - adverse effects; Pyrroles - therapeutic use; Regression analysis; Regression models; Rheumatoid arthritis; Risk assessment; Risk Factors; Surveillance; Thromboembolism; Thrombosis; Tumor necrosis factor; Tumor Necrosis Factor Inhibitors - adverse effects; Tumor Necrosis Factor Inhibitors - therapeutic use; Tumor necrosis factor-TNF; Venous Thromboembolism - epidemiology; Venous Thrombosis - chemically induced; Venous Thrombosis - epidemiology
• ISSN: 2326-5191; 2326-5205; 2326-5205
• DOI: 10.1002/art.42846

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 or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (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 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. Incidence rates were consistent across 6‐month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and 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. 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, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.