Preoperative Serum Vedolizumab Levels Do Not Impact Postoperative Outcomes in Inflammatory Bowel Disease (IBD)

Abstract

BACKGROUND: Although biological therapy has revolutionized the medical management of IBD, a crucial concern is whether patients undergoing major abdominal surgery after drug exposure are at increased risk of early postoperative complications. Studies reporting on the association of preoperative vedolizumab therapy use and postoperative outcomes in IBD have been published with conflicting results. Serum levels of anti-TNF drugs have been used as a surrogate for biologic effect on inflammatory mechanisms and have been correlated with postoperative outcomes. In a similar fashion, we sought to clarify associations between serum vedolizumab levels and postoperative outcomes in IBD patients. METHODS: IBD patients on vedolizumab, with serum drawn within 7 days before surgery, were identified from a prospectively collected IRB-approved database. Serum vedolizumab levels were measured by investigators blinded to clinical outcomes using the homogenous mobility shift assay (Prometheus Laboratories Inc.). Patients were divided into 2 groups according to serum levels: Group 1 (undetectable vedolizumab levels; ≤1.8 mcg/ml)) and Group 2 (detectable serum vedolizumab levels; >1.8 mcg/ml). To assess whether a higher level of vedolizumab affected outcomes, Group 2 was divided further into high and low levels as determined by median detectable serum level. Postoperative outcomes, including the Comprehensive Complication index (CCI)), within 30 days of surgery were collected prospectively and compared among groups. Categorical variables were analyzed using Fisher's exact test and continuous variables analyzed with Student's t-test. RESULTS: The study cohort of 35 patients had a median age of 29 (range, 14-62) years and included 18 (51%) males. Indications for surgery were Crohn's disease (n=18;51%), ulcerative colitis (n=14;40%) or indeterminate colitis (n=3;9%). Index procedures included subtotal colectomy with ileostomy (n=10;29%), small bowel/ileocolic resection (n=9; 26%) and ileal pouch-anal anastomoses (n=8;23%). Serum vedolizumab levels were detectable in 23 (66%) patients and not detectable in 12 (34%) patients. Median detectable serum vedolizumab level at the time of surgery was 12.6 mcg/ml (range, 1.9-54.4). Twelve (34%) patients had low detectable levels and 11 (31%) had high detectable levels. Groups 1 and 2 were similar in all preoperative characteristics. There were no postoperative deaths. There were no significant differences between groups in regards to overall postoperative morbidity (13% vs. 42%; P=0.09), infectious complications (4% vs. 17%; P=0.26), 30-day readmission rates after surgery (13% vs. 33%; P=0.19), or CCI (1.9 vs. 5.1; P=0.07). Finally, among patients with detectable serum vedolizumab levels, there was no association between level of vedolizumab (high vs. low) and overall postoperative morbidity (18% vs. 17%; P=1), infectious complications (0% vs. 8%; P=1), 30-day readmission rates (18% vs. 8%; P=0.59) or CCI (0.79 vs 2.9; P=0.07) after surgery. CONCLUSION(S): This first-ever study of serum vedolizumab levels in surgical patients showed that the presence and magnitude of serum drug levels do not adversely influence postoperative outcomes in IBD patients. Contrary to other studies, there appears to be no deleterious effect of preoperative vedolizumab use in IBD patients requiring surgery.