Controversy exists regarding the post-operative impact of systemic immunosuppressive agents in patients with inflammatory bowel disease (IBD), particularly relating to infection. Vedolizumab is a gut-selective monoclonal antibody targeting α4β7 integrin that is approved for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). Evaluation of the frequency of post-operative complications, including infection, associated with vedolizumab use will help inform treatment decisions for patients who may require subsequent bowel surgery. Here, we describe the post-operative safety profile of vedolizumab in clinical trial and post-marketing settings.Methods:
Clinical trial data from patients who underwent surgery during GEMINI I (UC) or II (CD) phase 3 studies, or an ongoing open-label extension (GEMINI OLE; UC and CD), were evaluated in an integrated analysis. GEMINI I and II patients received ≥1 dose of vedolizumab or placebo up to 52 weeks. GEMINI OLE enrolled patients who had previously participated in GEMINI I, II, III, or a phase 2 extension study, and a cohort of vedolizumab-naïve patients. In the post-marketing setting, all post-operative complications in UC/CD received from May 20, 2014 (first approval) to May 19, 2016 were evaluated. Post-operative complications were classified according to the Medical Dictionary for Regulatory Activities.Results:
In the phase 3 study population (N = 1731), 15/620 (2.4%) and 3/149 (2.0%) patients underwent colectomy (GEMINI I), and 36/814 (4.4%) and 4/148 (2.7%) bowel resection (GEMINI II), in the vedolizumab and placebo groups, respectively. Of those undergoing surgery, post-operative complications were reported in 3/51 (5.9%) patients receiving vedolizumab (n = 1 case each of post-operative wound infection, bacteremia and sepsis) and 1/7 (14.3%) of those receiving placebo (sepsis). Serious post-operative complications occurred in 1/51 (2.0%) and 1/7 (14.3%) patients receiving vedolizumab and placebo, respectively (both sepsis). In GEMINI OLE, 157/2243 (7.0%) patients underwent surgery. Among these, post-operative complications (cases of post-operative wound infection [n = 3], abdominal sepsis [n = 2], bacteremia [n = 1], sepsis [n = 1], septic shock [n = 1], post-operative ileus [n = 4], abdominal wound dehiscence [n = 2] and wound dehiscence [n = 1]) were reported in 11/157 (7.0%) patients. Serious post-operative complications (abdominal sepsis and abdominal wound dehiscence [n = 2 each] and single cases of sepsis, post-operative ileus, wound dehiscence, and post-operative wound infection) were reported in 6/157 (3.8%) patients. In the context of 46,978 patient-years exposure in the post-marketing setting, 20 post-operative reports from 19 patients were received: sepsis (n = 6), post-procedural complications (n = 4), impaired healing (n = 3), post-procedural hemorrhage (n = 2), and single cases of wound dehiscence, septic shock, wound infection, bacterial sepsis, and post-operative wound infection.Conclusions:
Despite the small sample size of the control group, these data suggest no clear differences in the frequency of post-operative complications between patients treated with vedolizumab and those receiving placebo in clinical studies. The frequency of events in the post-marketing setting is consistent with the rate expected in the treated IBD population. The small number of patients undergoing surgery in the clinical studies, and other limitations associated with post-marketing data collection (including voluntary nature of reporting and incomplete information provided by reporters), should be considered when interpreting these data.