Background: The risk of opportunistic infections (OIs) in IBD increases after treatment with biologics (OR: 1.90) . Vedolizumab (VDZ), a humanised monoclonal antibody, targets α4β7 integrin and selectively blocks gut-specific lymphocyte trafficking. Gut selectivity could be associated with a lower risk of infections compared with anti-TNFα agents, which cause systemic immunosuppression. We assessed the frequency of OIs with VDZ treatment in clinical trials and the post-marketing (PM) setting.
Methods: Safety data from GEMINI 1 and 2 (VDZ vs placebo, in ulcerative colitis [UC] and Crohn's disease [CD], respectively), the ongoing GEMINI open-label extension (OLE) study (VDZ only, UC and CD; data cut-off: 19 May 2015) and the VDZ Global Safety Database (May 2014 – 30 September 2016) were assessed. OI events were identified from a comprehensive list of MedDRA terms that are generally regarded as OIs.
Results: Seven OIs were reported in GEMINI 1 and 2 (N=1731); all received VDZ (n=1434). OIs included Clostridium difficile colitis (n=5); cytomegalovirus (CMV) colitis (n=1) and CMV infection (n=1). One event was serious; one (non-serious) led to discontinuation. 51 patients had OIs in GEMINI OLE (N=2243; TPY=5430; Table 1); C. difficile colitis was most frequent (n=26; serious: n=11; non-serious: n=15). In the context of ∼72,140 patient-years of VDZ therapy in the PM setting, 127 OI events were reported in 124 patients (serious: 59 events; non-serious: 68 events); the most frequently reported OI was C. difficile infection (74 events; 25 serious, 49 non-serious; Table 2). 2 patients had fatal OIs: Pneumocystis jiroveci pneumonia in a patient with immunosuppression due to long-term high-dose steroid use, and unspecified OI in a steroid-refractory graft versus host disease patient (off-label use). In the PM setting, VDZ treatment was continued in most patients with OI events (66%).
Conclusions: Clinical trial and PM data showed that OIs were infrequent with VDZ. The most common OI was C. difficile colitis/C. difficile infection: most events were non-serious; most patients continued VDZ. Limitations with PM safety reporting (e.g., limited details in case reports, increased likelihood of reporting more severe events) make confirming a causal association between drug and event difficult, and must be considered when interpreting the PM data.
 Bonovas S, (2016), Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis