P014 The safety profile of vedolizumab in ulcerative colitis and Crohn's disease: 4 years of post-marketing data

BACKGROUND: Vedolizumab is a gut-selective antibody to α4β7 integrin approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in adults. The safety and efficacy of vedolizumab have been demonstrated in 3 phase 3, randomized trials (NCT00783718, NCT00783692, and NCT01224171), but these only included patients meeting eligibility criteria, who may not reflect real-world clinical practice. Here, we describe the first 4 years of post-marketing safety data reported to Takeda Pharmaceutical Company Ltd (Takeda). METHODS: The Vedolizumab Global Safety Database contains all adverse event (AE) reports received by Takeda since vedolizumab was approved on 20 May 2014. Reports received between approval and 19 May 2018 were identified using Medical Dictionary for Regulatory Activities version 21.0. Vedolizumab exposure was calculated based on the number of vials shipped globally, assuming 8-week dosing intervals. RESULTS: In approximately 208,050 patient-years of vedolizumab exposure, 80,218 AEs were reported in 32,752 patients. Of these AEs, 37,662 (47%) and 34,259 (43%) were in patients with CD and UC, respectively, while 8,297 (10%) were in individuals receiving vedolizumab for other indications (off-label use) or without a reported indication. Gastrointestinal AEs were the most common type reported in patients with CD (6,156 [16%]) and UC (5,701 [17%]). There were 5,230 (14%) serious AEs in patients with CD and 3,580 (10%) in patients with UC; most commonly related to exacerbation of underlying disease (CD, 406 patients [8%] and UC, 410 [11%]). Infusion-site reactions were reported in 211 patients with CD and 186 with UC, and lupus-related AEs in 10 and 9 patients, respectively. Malignancies were reported in 140 patients with CD and 123 with UC; those most commonly reported were lower gastrointestinal (23 patients [16%] and 34 [27%], respectively). Hepatobiliary AEs were reported in 152 patients with CD and 177 with UC. Infections were reported in 3,064 patients with CD and 2,812 with UC; of these, 710 (23%) and 427 (15%), respectively, were serious. Opportunistic infections were reported in 95 patients with CD and 193 with UC, including one case of progressive multifocal leukoencephalopathy in a patient with CD and untreated HIV receiving long-term immunosuppressant treatment using other agents. Infections of particular clinical significance were reported in low numbers, with nocardiosis and histoplasmosis reported in 2 and 9 patients with CD, respectively, and tuberculosis reported in 5 patients with CD and 4 with UC. Of the 652 pregnancy-related reports, 46% had an associated AE; the most common was spontaneous abortion (48 reports). There were 10 reported congenital abnormalities. Of the patients with CD or UC reporting AEs, 74% continued vedolizumab treatment. CONCLUSION(S): These data suggest that the favorable safety profile of vedolizumab in CD and UC in the post-marketing setting is consistent with that established in clinical trials. Limitations of post-marketing safety reports, including incomplete data, voluntary reporting, increased reporting of serious vs non-serious AEs and difficulty establishing a causal relationship between drug and event, must be considered when interpreting these results. Most reported AEs with vedolizumab were non-serious, and frequencies of AEs of particular clinical interest appeared low.