Tofacitinib Treatment Before Colectomy Carries Minimal Postoperative Complication Risk

Findings from a recent study are providing clinicians with novel insight into the postoperative safety profile of tofacitinib in patients with ulcerative colitis (UC) undergoing colectomy.1

Results published in The American Journal of Gastroenterology showed no significant differences between tofacitinib, anti-tumor necrosis factor-α (TNF)s, vedolizumab, and ustekinumab for early and late complications, infections, and sepsis following surgery.¹

“To the best of our knowledge, this is the first study assessing the safety of preoperative exposure to tofacitinib in comparison with biologics in patients with UC undergoing colectomy,” lead investigator Gabriele Dragoni, MD, PhD, a gastroenterologist at Careggi University Hospital in Italy, and colleagues wrote.¹

For patients with UC who do not respond to medication or develop complications of colitis, colectomy may be necessary. The procedure carries a risk of serious complications, but the impact of preoperative tofacitinib treatment on postoperative risk has not been thoroughly explored.²

To assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics, investigators conducted a multicenter, retrospective, observational study of patients with medically refractory UC who underwent total colectomy at 27 centers across Europe between September 2005 and February 2023. For inclusion, patients were required to have an established diagnosis of UC; medically refractory UC as the reason for surgery; administration of the last dose of tofacitinib within 4 weeks of colectomy; or administration of the last dose of biologics within 12 weeks prior to colectomy.¹

Tofacitinib, anti-TNFs (infliximab, adalimumab, and golimumab), vedolizumab, and ustekinumab were considered active treatment. The primary outcome was the occurrence of any postoperative complications within 30 and 90 days after surgery, defined by investigators as early and late, respectively. Secondary outcomes included the occurrence of infections, sepsis, surgical site complications, venous thromboembolism (VTE), unplanned hospital readmissions, redo surgery, and death within the same predefined time points.¹

In total, 301 patients were included in the study. Among the cohort, 64 (21.3%) patients were in the tofacitinib group, whereas 237 were on biologics: 162 (53.8%) in the anti-TNF group, 54 (17.9%) in the vedolizumab group, and 21 (7.0%) in the ustekinumab group.¹

Administration of the last dose of tofacitinib occurred at a median time of 13 (Interquartile range [IQR], 4–20) days before surgery, whereas the last dose of anti-TNF, vedolizumab, and ustekinumab was administered at a median of 21 (IQR, 14–38), 34 (IQR, 18–50), and 27 (IQR, 16–31) days before surgery, respectively. In total, 90 (29.9%) patients had ≥ 1 early complication, including infections (13.3%); sepsis (5.6%); surgical site complications (17.6%); VTE (3.0%); hospital readmission (8.6%); and redo surgery (6.6%). Additionally, 26 (8.5%) patients had ≥ 1 late complication between 30 and 90 days after surgery, including infections (1.7%); sepsis (0.3%); surgical site complications (3.6%); VTE (0.7%); hospital readmissions (5.6%); and redo surgeries (1.3%).¹

Upon analysis, there were no statistically significant differences in the occurrence of any early (P = .07) and late (P = .67) complications between the 4 treatment groups. For secondary outcomes, investigators observed a greater rate of early VTE with anti-TNF agents (P = .047) and late VTE with vedolizumab (P = .03).¹

Further analysis revealed urgent colectomy provided a higher risk of any early complications (Odds ratio [OR], 1.92; 95% CI, 1.06–3.48; P = .03). However, a subanalysis of separate complications showed urgent colectomy only increased the risk of early hospital readmissions (OR, 4.79; 95% CI, 1.12–20.58; P = .04), and early redo surgery (OR, 7.49; 95% CI, 1.17–47.85; P = .03).¹

Investigators noted a steroid dose greater than the equivalent of 20 mg of oral prednisone increased the risk of any early complications (OR, 1.96; 95% CI, 1.08–3.57; P = .03), early surgical site complications (OR, 2.03; 95% CI, 1.01–4.09; P = .048), and early redo surgery (OR, 7.52; 95% CI, 1.42–39.82; P = .02). They further pointed out laparoscopic surgery reduced the risk of any early complications (OR, 0.54; 95% CI, 0.29–1.00), early infections (OR, 0.39; 95% CI, 0.18–0.85), and late hospital readmissions (OR, 0.34; 95% CI, 0.12–1.00) compared to other types of surgery.¹

Notably, the class of drug did not influence the risk of any early or late complications in the multivariate analysis. Investigators pointed out anti-TNF agents resulted in a protective effect for early hospital readmission, although similar rates were observed between groups and very few events occurred.¹

Investigators called attention to several potential limitations to these findings, including the retrospective study design, inability to perform propensity score matching and simulate the effect of randomization, potential selection bias, and the short half-life of tofacitinib.¹

“Our data demonstrated that tofacitinib and biologics have a similar rate of adverse events in the postoperative setting of patients undergoing colectomy for medically refractory UC. Urgent surgery and high doses of steroids before surgery were confirmed to be associated with a higher risk of early surgical complications,” investigators concluded.¹

References:

1. ^{Dragoni G, Innocenti T, Aurelién A, et al. Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study. The American Journal of Gastroenterology. doi:10.14309/ajg.0000000000002676}
2. ^{Mayo Clinic. Colectomy. Tests & Procedures. November 8, 2022. Accessed April 10, 2024. https://www.mayoclinic.org/tests-procedures/colectomy/about/pac-20384631}