DOP024 Vedolizumab clinical and post-marketing safety experience of opportunistic infections

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Background: The risk of opportunistic infections (OIs) in IBD increases after treatment with biologics (OR: 1.90) [1]. 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.


[1] Bonovas S, (2016), Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis

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