P735 Incidence of venous thromboembolic complications in controlled trials of inflammatory bowel disease

Abstract

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolic (VTE) complications compared with the general population. Incidences of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients with IBD are reported as 30.0-31.4/10 000 person-years (p-y) and 10.3-19.8/10 000 p-y, respectively.1 To date, no study in patients with moderateto-severe IBD has examined incidence of VTE complications in a controlled clinical setting. We aimed to evaluate the incidence of thromboembolic events across five clinical trials of an anti-MAd-CAM monoclonal antibody (SHP647) in patients with IBD. Methods: Data were pooled from five clinical trials of SHP647 in patients with Crohn's disease (CD) and ulcerative colitis (UC) (NCT01276509; NCT01298492; NCT01387594; NCT01620255; NCT01771809). Three were 12-week induction studies, and two were open-label extension studies lasting 18-36 months. One study (NCT01771809) is ongoing. Patients had moderate-to-severe disease (CD: CDAI 220-450; UC: total Mayo score > 6). All adverse events were collected and coded using the Medical Dictionary for Regulatory Activities (MedDRA) system. The safety database was searched using Standardised MedDRA Query terms of: Embolic and Thrombotic events; Arterial, Embolic and Thrombotic events; and Venous and Ischaemic Central Nervous System Vascular Conditions. Person-years of exposure were calculated to include a 6-month post-treatment follow-up period, owing to the long half-life of the drug (5-9 days). Results: In total, 668 patients were enrolled across the five clinical trials (CD, n = 311; UC, n = 357). Placebo exposure was 35.4 p-y, while drug exposure was 1005.1 p-y. There were 17 thromboembolic events reported overall: 5 arterial and 12 venous. One event (PE in a 26-year-old woman treated with SHP647 225 mg) was fatal. The incidences of DVT and PE are presented in Table 1. The incidence of VTE appeared higher for CD than UC (risk ratio [95% CI] of events/p-y of exposure: 2.4 [0.88, 6.65]). Conclusions: The overall incidences of DVT and PE in these five trials of SHP647 were within the range reported for the overall IBD population, when considering the wide-ranging confidence intervals. The total numbers of events in the UC, CD and placebo groups were small and insufficient for robust conclusions on relative rates.