Tofacitinib Is Associated With Increased Risk of Postoperative Venous Thromboembolism in Patients With Ulcerative Colitis

Abstract

BACKGROUND: In 2019, the Food and Drug Administration issued a black box warning for increased risk of venous thromboembolism in rheumatoid arthritis patients exposed to tofacitinib. There is limited data regarding the postoperative venous thromboembolism risk in ulcerative colitis patients exposed to tofacitinib. OBJECTIVE: To assess if preoperative exposure to tofacitinib is associated with increased odds of postoperative venous thromboembolism. DESIGN: Retrospective review. SETTINGS: Tertiary academic medical center. PATIENTS: Consecutive patients exposed to tofacitinib within 4 weeks prior to total abdominal colectomy or total proctocolectomy, with or without ileostomy, from 2014 to 2021, matched 1:2 for tofacitinib exposure or no exposure. INTERVENTION: Tofacitinib exposure versus no exposure. MAIN OUTCOME MEASURES: Ninety-day postoperative venous thromboembolism rate. RESULTS: Forty-two patients with tofacitinib exposure and 84 case-matched patients without tofacitinib exposure underwent surgery for medically-refractory ulcerative colitis. Nine (22.0%) tofacitinib exposed patients, and 7 (8.5%) unexposed patients, were diagnosed with a venous thromboembolism within 90-days of surgery. In univariate logistic regression, patients exposed to tofacitinib had 3.01 times increased odds of developing a venous thromboembolism within 90-days following surgery compared to unexposed (p = 0.04, 95% CI 1.03-8.79). Other venous thromboembolism risk factors were not significantly associated with venous thromboembolisms. Venous thromboembolisms in both groups were most commonly portomesenteric vein thromboses (66.7% in tofacitinib exposed and 42.9% in unexposed) and were diagnosed at a mean of 23.2 days (range, 3-90 days) postoperatively in the tofacitinib exposed and 7.9 days (1 to 19 days) in the unexposed groups, respectively. There were no statistically significant differences in location or timing between the 2 groups. LIMITATIONS: Retrospective nature of the study and associated biases. Reliance on clinically diagnosed venous thromboembolisms may underreport true incidence rate. CONCLUSIONS: Tofacitinib exposure prior to surgery for medically-refractory ulcerative colitis is associated with 3 times increased odds of venous thromboembolism as compared to patients without tofacitinib exposure. See Video Abstract.