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* = Presenting author

P647 Tuberculosis in patients treated with vedolizumab: clinical trial and post-marketing case series

Zerôncio M.*1, Blake A.2, Rana-Khan Q.3, Palo W.4, Bhayat F.5

1Clínica de Oncologia de Natal, Gastroenterology, Natal, Brazil 2Takeda Development Center Europe Ltd, Global Pharmacovigilance, London, United Kingdom 3Takeda Pharmaceutical International AG Singapore, Emerging Markets Medical Affairs, Singapore, Singapore 4Takeda Development Center Americas, Inc., Global Statistics and Statistical Programming, Deerfield, United States 5Takeda Development Centre Europe Ltd, Global Pharmacovigilance, London, United Kingdom

Background

Treatment with anti-tumour necrosis factor-alpha (anti-TNFα) agents has been shown to increase the risk of reactivating latent infections, especially tuberculosis (TB) [1]. Vedolizumab (VDZ) is a humanised monoclonal antibody that targets α4β7 integrin and selectively blocks gut-specific lymphocyte trafficking. This gut selectivity may be associated with a lower risk of reactivating latent infections compared with anti-TNFα agents, which cause systemic immunosuppression. Here we describe the frequency of TB with VDZ therapy in clinical trials and the post-marketing (PM) setting.

Methods

Safety data from the GEMINI 1 and 2 studies (VDZ vs placebo, in ulcerative colitis [UC] and Crohn's disease [CD], respectively), the ongoing GEMINI open-label extension (OLE) study (VDZ only, both UC and CD; data cut-off: 21 May 2015) and PM data from the VDZ Global Safety Database (May 2014–31 August 2016) were assessed. TB infections were classified according to MedDRA.

Results

In GEMINI 1, 2 and OLE, 6 TB events were reported in 5 patients (serious: n=4; non-serious: n=1; Table 1), with 4 TB events considered treatment-related. Patients with TB were in the Czech Republic (n=1), India (n=1), Republic of Korea (n=1), Russian Federation (n=1) and Slovakia (n=1). All TB events resulted in treatment discontinuation, as per study protocol. In the context of ∼66,390 patient-years of VDZ therapy in the PM setting, 5 patients (Table 2) reported TB (serious: n=4; non-serious: n=1): 2 patients permanently discontinued treatment, 2 discontinued and later restarted, and 1 was not reported (discontinuation recommended in product label). Of the 5 patients in the PM setting, 2 had previously received anti-TNFα agents (infliximab: n=1; adalimumab: n=1). The PM TB events occurred in the US (n=3), France (n=1) and Germany (n=1).

Table 1. TB cases in clinical studies*

Table 2. TB cases in the PM setting

Conclusion

The frequency of TB in VDZ clinical trials and the PM setting was low. Clinical trial events occurred in countries where TB incidence is higher than in the US, while the origin of PM reports is likely to be explained by the greater exposure in those countries. Limitations associated with PM safety reporting (e.g. incomplete co-morbidity and co-medication data), which make confirming a causal association between drug and event difficult, must be considered when interpreting the PM results.

References:

[1] Solovic I, Sester M, Gomez-Reino JJ, et al. (2010), The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement, Eur Respir J, 1185–26