Background: Vedolizumab (VDZ) is a humanised monoclonal antibody that binds to α4β7 integrin and selectively blocks gut-specific lymphocyte trafficking. Although upper respiratory tract infections (URTIs) have been reported with VDZ  its gut selectivity may reduce the risk of respiratory tract infections (RTIs), including pneumonia, compared with therapies producing systemic immunosuppression (e.g. anti-tumour necrosis factor-alpha [TNFα] agents). We aimed to determine the incidence of RTIs associated with VDZ treatment in the clinical trial setting.
Methods: Safety data from VDZ phase 3 randomised controlled trials (RCTs) in ulcerative colitis (UC; GEMINI 1) and Crohn's disease (CD; GEMINI 2) and a phase 3 open-label extension (OLE; C13008 ongoing study in both UC and CD) were used to calculate the incidence of lower RTIs (LRTIs), including pneumonia, and URTIs using the MedDRA High Level Terms “lower respiratory tract and lung infections” and “upper respiratory tract infections”. A Cox proportional hazards model was used to identify potential predictors of these AEs for the pooled GEMINI 1 and 2 results.
Results: Of 1731 patients in the pooled RCT population and 2243 patients in the OLE, mean (SD) ages were 37.9 (12.7) years and 39.1 (13.2) years, respectively; 43% and 50%, respectively, had disease duration ≥7 years; and 57% and 59%, respectively, had prior anti-TNFα therapy. In the RCTs, the rate of LRTIs, including pneumonia, was similar in the VDZ and placebo groups (Table 1). Rates of LRTIs were higher for VDZ-treated patients with CD than with UC. Most LRTI and URTI AEs were not serious and did not result in treatment discontinuation. Predictors of increased incidence of LRTIs were identified as being a current or former smoker, female sex and prior anti-TNFα therapy (Table 2). Predictors of URTIs were: being a current smoker, concomitant narcotic use and prior anti-TNFα therapy.
Conclusions: In this post hoc analysis, VDZ treatment of IBD was not associated with an increased incidence of LRTIs, including pneumonia, compared with placebo. Continuing pharmacovigilance will supplement these data and ongoing observational studies will further characterise these findings.
 Takeda Pharmaceuticals America, Inc. (2014), ENTYVIO® (vedolizumab) Prescribing Information